14.15: Introduction to the Father of Genetics - Biology

Identify the impact of Gregor Mendel on the field of genetics and apply Mendel’s two laws of genetics

Gregor Mendel is often referred to as the Father of Genetics. But just what did he do to earn this honorary title? In this outcome we’ll examine the work he did and how his work still impacts genetics today.

What You’ll Learn to Do

  • Describe Mendel’s study of garden peas and hereditary
  • Understand how the inheritance of a genotype generates a phenotype
  • Apply the law of segregation
  • Apply the law of independent assortment

Learning Activities

The learning activities for this section include the following:

  • Mendel’s Experiments and Heredity
  • Characteristics and Traits
  • Laws of Inheritance
  • Heredity
  • Self Check: The Father of Genetics

Gregor Johann Mendel was born Johann Mendel on July 20, 1822, to Anton and Rosine Mendel, on his family’s farm, in what was then Heinzendorf, Austria. He spent his early youth in that rural setting, until age 11, when a local schoolmaster who was impressed with his aptitude for learning recommended that he be sent to secondary school in Troppau to continue his education. The move was a financial strain on his family, and often a difficult experience for Mendel, but he excelled in his studies, and in 1840, he graduated from the school with honors.

Following his graduation, Mendel enrolled in a two-year program at the Philosophical Institute of the University of Olmütz. There, he again distinguished himself academically, particularly in the subjects of physics and math, and tutored in his spare time to make ends meet. Despite suffering from deep bouts of depression that, more than once, caused him to temporarily abandon his studies, Mendel graduated from the program in 1843.

That same year, against the wishes of his father, who expected him to take over the family farm, Mendel began studying to be a monk: He joined the Augustinian order at the St. Thomas Monastery in Brno, and was given the name Gregor. At that time, the monastery was a cultural center for the region, and Mendel was immediately exposed to the research and teaching of its members, and also gained access to the monastery’s extensive library and experimental facilities.

In 1849, when his work in the community in Brno exhausted him to the point of illness, Mendel was sent to fill a temporary teaching position in Znaim. However, he failed a teaching-certification exam the following year, and in 1851, he was sent to the University of Vienna, at the monastery’s expense, to continue his studies in the sciences. While there, Mendel studied mathematics and physics under Christian Doppler, after whom the Doppler effect of wave frequency is named he studied botany under Franz Unger, who had begun using a microscope in his studies, and who was a proponent of a pre-Darwinian version of evolutionary theory.

In 1853, upon completing his studies at the University of Vienna, Mendel returned to the monastery in Brno and was given a teaching position at a secondary school, where he would stay for more than a decade. It was during this time that he began the experiments for which he is best known.

Genetic epidemiology of asthma

Looking at the population gives clues about asthma being a heritable trait. First, there are large geographic and racial differences in disease occurrence. For example, the prevalence of asthma in many Western populations is high, up to 20%, whereas populations from the developing world exhibit much smaller prevalence rates, some as low as 1% or even lower (2). This is only indicative of a genetic causation in asthma, as different populations also have very different environmental circumstances. Second, offspring of asthmatic parents are at increased risk of asthma ( Table 1 ). The recurrence risk of asthma in children with one affected parent is around 25%, whereas the risk if both parents are affected is around 50%. Twin studies also support asthma being much more likely to occur in an individual if that individual has a genetically close relative with the disease. For instance, the recurrence risk of asthma in monozygotic twins is much higher than in dizygotic twins, highlighting the role of genetic risk factors in asthma (3). Nevertheless, the fact that the concordance for asthma in monozygotic twins is not 100% – but around 75% – points to environmental risk factors also playing an important role.

Table 1

Recurrence risk of asthma

Affected relativePerson's own risk of asthma (%)
No family history5
Half sibling10
Full sibling25
One parent25
Dizygotic twin35
Two parents50
Monozygotic twin75

While it is obvious that the individual risk of asthma is dependent on familial background, the phenotypic expression of asthma may be modified by other genetic and environmental factors. It is deemed that a small number of genes set the individual background risk that is acted upon by another set of modifying genes and also environmental factors. For example, individuals with early-onset asthma more frequently have a family history of asthma than do those with later-onset asthma, suggesting that genes influence the age at onset of the disease (4). In addition, the severity of asthma as judged by symptom frequency, level of lung function, degree of airway responsiveness and airway inflammation, aggregates within families, which suggests that if a person has a positive family history of severe asthma, that person is more likely to develop severe asthma (5).

1. Principles of Inheritance and Variation: As the name itself conveys, this chapter of genetics and evolution deals with the laws and theories of inheritance and variation. An arduous and fascinating description of the experiments performed by Gregor Johann Mendel, the father of genetics, is worth reading, understanding and applying in different situations. The laws so formulated, that is, the law of dominance, law of segregation and law of independent assortment talk about the rules of transmission of heredity information. Thereafter, there are some processes showing deviation from Mendelian laws. The sex determination based on genetical as well as non-genetical factors is also discussed. Lastly, there is a discussion on the chromosomal disorders based on the Mendelian laws. Therefore, the topics can be summarised as:

Crack JEE 2021 with JEE/NEET Online Preparation Program

  • Heredity and variation
  • Deviations from Mendelism-Incomplete dominance, Co-dominance, Multiple alleles and Inheritance of blood groups, Pleiotropy
  • Elementary idea of polygenic inheritance
  • Chromosome theory of inheritance
  • Chromosomes and genes
  • Sex determination-In humans, birds, honey bee
  • Linkage and crossing over Sex-linked inheritance-Haemophilia, Colour blindness
  • Mendelian disorders in humans-Thalassemia
  • Chromosomal disorders in humans Down&rsquos syndrome, Turner&rsquos and Klinefelter&rsquos syndromes.

Hence, as you can already infer, the quantum of concepts is quite large and all the topics need a conceptual understanding. A mug-up of the concepts would limit your ability to apply them in different situations and this would be a big let-down in NEET exam. Therefore, take your time and prepare the topics with patience.

2. Molecular Basis of Inheritance: It would be appropriate to say that this chapter of genetics and evolution is the molecular version of what you have studied in the previous chapter. Hence, this chapter deals with the molecular structure of the vehicles of transmission of heredity characters - DNA (deoxyribonucleic acid). The historical experiments that were performed to find out the genetic material are elaborately described and these are crucial for the NEET exam perspective. The Watson-Crick Model is the essence of DNA structure and it offers a whole variety of questions in the NEET exam. The structure of RNA is also described. Further, you will be introduced to the spell-bounding central dogma of molecular biology. This will open up the pathway of transmission of information from the molecular structure of the DNA to the visible features of an organism. The applications of the information stored in the DNA molecules are vast and still untapped. One such application of DNA fingerprinting would be introduced in this chapter. A successful quest of molecular biologists to read the DNA of humans, that is, the Human Genome Project and its significance is also the feature of this chapter.

In all, the topics of this chapter of genetics and evolution can be summarised as:

  • Search for genetic material and DNA as genetic material:
  • Transforming Principle of Frederick Griffith, Biochemical Characterisation of Transforming Principle performed by f Oswald Avery, Colin MacLeod, and Maclyn McCarty, experiments of Alfred Hershey and Martha Chase.
  • Structure of DNA and RNA
  • Properties of Genetic Material (DNA versus RNA): ) It should be able to generate its replica (Replication), It should be stable chemically and structurally, It should provide the scope for slow changes (mutation) that are required for evolution, It should be able to express itself in the form of 'Mendelian Characters&rsquo
  • DNA packaging
  • DNA replication: Experimental proof by Matthew Meselson and Franklin Stahl The Machinery and the Enzymes for replication Replicating Fork
  • Central dogma
  • Transcription: Transcription Unit, Types of RNA and the process of Transcription
  • Genetic code: The salient features of genetic code, Mutations and Genetic Code
  • Translation
  • Gene expression and regulation-Lac Operon
  • Genome and human genome project
  • DNA fingerprinting

Hence, this chapter of the molecular basis of inheritance provides a wide range of conceptual topics. This would also be a time-taking chapter to prepare. However, investment of time in this topic should not be feared as this will be very helpful for NEET exam.

3. Evolution: This is the story of the origin of life and evolution of life forms or biodiversity on planet earth in the context of the evolution of earth and against the background of the evolution of the universe itself. This is a theoretical chapter that brings up the concepts of genetics into understanding the evolution of various life forms. There are the following topics in this chapter of genetics and evolution:

God, Family, and Genetics – A Biblical Perspective

This article is taken from the proceedings of the symposium 'The Two Shall Become One' held in Rome in September 2015, jointly sponsored by Human Life International and the Kolbe Center for the Study of Creation.

God, Family, and Genetics – A Biblical Perspective

Part One: Genetic Evidences Supporting the Divine Origin of Man and Family

Dr. J.C. Sanford i and Dr. Robert Carter ii
i Cornell University, Hedrick Hall, NYSAES, Geneva, NY 14456 USA
ii FMS Foundation, 877 Marshall Rd., Waterloo, NY 13165 USA

This is the first part of a two-part paper. The second part (also in this volume) is entitled: God, Family, and Genetics – A Biblical perspective: Genetic Evidences Refuting the Evolution of Man and Family. Drawn in part from Sanford and Carter (Christian Apologetics Journal, Vol. 12, No. 2, 2014).


The family is, and always has been, the most fundamental unit of human society. The family is also a fundamental element of the Christian faith. God has revealed Himself as our Heavenly Father, and He has given to us the right to be “Children of God”. God’s design for the family is revealed in His perfect creation. God teaches us that in the beginning He made a special man, and from him he made a special woman, and they were united as one flesh. He created them in His own image, and they were destined to be the Father and Mother of us all. The Church has consistently affirmed these elements of Scripture and has affirmed these things as foundational doctrine. Is the Church now going to abandon this doctrinal foundation?

As we read God’s Word, we see that soon after the creation of that special couple, the first family was deceived and fell into sin, bringing death and suffering into the world. Cain, the first-born, entered a corrupted world. He soon murdered his younger brother. The first family became a broken family. The Bible describes many such broken families. Sadly, there are now countless broken families in the world today.

When Jesus came, He showed us what a restored family should look like. The Faithful Father. The Faithful Mother. The Faithful Son. The call to radical love. The call to radical sexual fidelity. The call to respect one’s parents. The call to help support one’s children. The call to protect children from sin and to “bring them up in the nurture and admonition of the lord” (Eph 6:4). The call for parents to produce godly children. These are the things that God’s Word reveals to us in terms of what a healthy, godly family should look like.

Today the family is being besieged like never before –on a global scale. A large fraction of all babies that are conceived are aborted by their mother. A large fraction of all babies that are born, do not enter into any sort of functional family. The mother is very commonly not married and often lacks radical commitment to the father or even to the child. Likewise, the father is often not radically committed to either the mother or the child. Even if the father and mother are married, there is too high a probability they will not stay married. The child will very likely be exposed at an early age to pornography in the home. The child will very commonly witness sexual immorality within the home. At a very young age, many children will be encouraged through television, Internet, and school to explore sexual sin, sodomy and much more. Heaven help today’s children!

Modern social engineers have helped create this moral crisis, and they are now aggressively imposing their social agenda on the entire world. This agenda includes complete sexual liberation, normalization of sodomy, and redefinition of marriage. Redefinition of marriage fundamentally means redefining (and further degrading) family. This is a direct attack on Christianity, especially in light of Eph 5:32 where Paul equates the “profound mystery” of marriage to the relationship between Christ and his bride. How will the Church respond?

A large part of the Christian world has turned a blind eye to this profound moral crisis. But isn’t the Church called to shine the light of Jesus into this dark world, and provide some type of moral compass? Tragically, much of the Church appears to be ill equipped and unwilling to do anything more than “go with the flow”. Will the Catholic Church also simply “go with the flow”? Or will the Catholic Church stand firm, championing the teachings of God’s Word and the wisdom of almost 2000 years of Church teaching?

The Church has a very solid foundation on which to defend the family. That foundation is clearly presented in God’s Word, starting with the very first family, prior to the Fall. A large part of the moral crisis that now threatens to destroy the family results from the widespread rejection of the authority and historicity of the Bible. However, by God’s grace there are now many evidences that support the authority and historicity of the Bible. This includes growing genetic evidence that the first family, Adam and Eve, really did exist, and that they really were the Father and Mother of us all. In God’s perfect timing, He is confirming the reality of the first model family so that the Church may be emboldened to stand firm regarding the biblical and historical model of family.

Before we summarize the scientific evidence supporting the biblical view of family, we need to make one thing very clear. The “scientific consensus” as it stands today, will reject any and all evidence for a literal Adam and Eve. It is crucial that Church leaders understand that scientists and scientific communities represent fallen, fallible people. While the scientific method is objective, scientists are not. Scientists are subject to group psychology, political influence, and spiritual influence. Historically, scientific communities have sometimes been subject to bigotry and have represented ideologically-driven hierarchical power structures. The eugenics movement that was founded by Darwin’s direct associates, the claims of the Nazi leadership concerning inferior and superior races, and the scientific consensus within the Soviet Union under Stalin that led to environmental degradation and mass starvation did not reflect objective scientific analysis. The claims of these scientific communities were scientifically wrong and were politically and spiritually motivated. “Scientific consensus” can sometimes just mean the group-think of the currently ruling intellectual power elite. A scientific consensus can often reflect a changing and very fickle intellectual sub-culture. The popular ideas that dominate the current scientific sub-culture must not be confused with either the scientific method itself or objective “Truth.”

At this moment the majority of western scientists are militantly promoting sexual liberation, abortion, and sodomy. Moreover, they are generally hostile to Jesus, the Bible, and the Church. This is very different from the scientific consensus in previous decades, and is radically different from scientific consensus in previous centuries. A strong consensus like this does not necessarily mean that the opinions of the currently reigning authorities are correct. We must remember that human authority is fallible. Jesus was crucified by the secular and religious authorities of His day.

In many cases, most of the people who make up a scientific consensus are not even well informed on the relevant technical issues. Many “authorities” are themselves just following their peers. Quite often they have never even examined the other point of view or the conflicting evidence. Therefore, when Christians are defending the Christian faith in terms of specific scientific claims, we need to remember the power that group-think can have on even the highest human authorities. The Church needs to honestly examine both sides of the scientific issue at hand but must also carefully consider the spiritual dimensions of the issue and must examine the moral posture of the antagonists.

When scientific authorities challenge fundamental Church doctrines, they act as if the burden of proof is always on the Church. But it should be just the opposite. From the Church’s point of view the burden of proof must lie with the challengers of The Faith. How much evidence is needed to justify overthrowing a foundational Church Doctrine? Is there any human argument sufficient for such a purpose? How much scientific evidence is needed to uphold a fundamental Church Doctrine? Isn’t even one honest and coherent scientific argument sufficient? We now have many honest and coherent genetic arguments that support the biblical view of the first family. So shouldn’t Church leaders eagerly wish to examine these arguments carefully, and shouldn’t they be predisposed to embrace those arguments - to the extent that reason and integrity permit?

By God’s grace He is giving us strong scientific evidences that support the biblical perspective of family which has always formed the basis for the Church’s doctrine on Holy Marriage and the family. For this reason Church leaders can honestly and rationally stand fast in upholding the fundamental doctrines of the faith regarding God’s design for the first family, and God’s design for the restoration of the modern family.

Part one of this two-part paper will summarize a series of powerful genetic evidences that support the physical reality of Adam and Eve – the first family. Part two (in this same volume) will summarize a series of powerful genetic evidences that refute the evolutionary view of early man and the evolutionary perspective regarding the origin of family.

Genetic Evidences Supporting the Biblical Perspective of Man and Family

Remarkably, when we examine the genetic make-up of modern human populations, we find strong genetic evidence that supports the reality of a literal Adam and a literal Eve. In addition we see evidence of a literal Fall (implying a previously perfect creation). Modern genetic studies also provide evidences supporting other aspects of the biblical account, specifically relating to the recent emergence of the human race and of humanity’s various people groups. Below we will outline seven Bible-affirming genetic evidences.

Because most of the people who will read this paper are not geneticists, it is helpful to review some genetic terms. The human body is like an extremely sophisticated robotic system that is programmed to do everything that is required for sustaining life. Due to the sheer complexity of the system, the hardware and software that enable human life is probably beyond human understanding. Much of the programmed information required to sustain the human body (and mind) is stored in the genome. The genome is like a large library of information, or, even better, a computer operating system. It is written out in a molecule called DNA, which consists of long text strings of molecular letters (nucleotides). The human genome consists of two complete sets of information – each with more than 3 billion letters. The genome is broken down into 23 different pairs of chromosomes – which are like individual book volumes of the library. Each chromosome has thousands of genes - which are like book chapters. Each gene consists of 50,000 to 1 million letters (nucleotides) – and is really more like an executable computer program that the chapter of a book. Mutations are like word-processing errors. When a mutation happens, a specific letter (a nucleotide that helps encode a necessary biological function) is accidentally replaced by a different (incorrect) letter. All the information in the genome (including the mutations) is passed from cell to cell as the body develops, and eventually from parent to child.

The small mitochondrial chromosome is exceptional in that it is only passed down through the mother, yielding a historical record of the matrilineal lineage of humanity. The Y chromosome is exceptional in that it is only passed down from father to son, yielding a historical record of the patrilineal lineage of humanity. These two small chromosomes have become the two most important tools for exploring human ancestry and for drawing conclusions about human history.

1. Genetic evidence that there was a literal Eve, the mother of us all.

Many evolutionists now regret having coined the term “Mitochondrial Eve”, which was meant to be a tongue-in-cheek slap at the biblical perspective. But now all geneticists agree that there is but one mother of us all. [1] We have statistically analyzed over 800 human mitochondrial sequences from around the world, and have been able to reconstruct and publish a very close approximation of Eve’s mitochondrial sequence. [2] Using this sequence, we discovered that the average human being has only diverged from the original Eve sequence by about 22 mutations (although some individuals are as much as 100 mutations different from Eve). Figure 1 illustrates how accumulating mutations within our mtDNA have caused each one of us to divergence from the original Eve sequence. As time passes, we are all slowly getting further and further from the original Eve sequence as mutations accumulate.

Can we account for this amount of mutation arising within a biblical timeframe? Easily. The most recent estimate of the mutation rate within the human mitochondrial DNA is about 0.5 mutations per generation. [3] Thus, even for those individuals with the most mutated sequences (100 mutations different from Eve), it would only require 200 generations (less than 6,000 years) to accumulate this many mutations. This simple calculation is based upon the most straightforward application of the “molecular clock” concept (which assumes mutations accumulate at a constant rate). If mutation rates were faster in the past, and there are multiple ways for this to happen, it would require even less time to accumulate 100 mutational differences. But the actual average distance is just 22 mutations – reducing the required time by four-fold. This means that even if many of the mutations were being removed by natural selection, there would still plenty of time for this much mutational damage to accumulate in a biblical timeframe.

The Bible states that all people on earth can trace their ancestry to a single woman, Eve. Thus, we would predict that a single ancestral mitochondrial sequence should be readily recognized within every human being, and this is exactly what is seen. But clear genetic evidence of a singular “mother of us all” is NOT a reasonable expectation given the evolutionary perspective. In fact, given standard evolutionary assumptions, there should be many ancient mitochondrial types. It is claimed that humanity first came out of Africa over 1 million years ago and diverged into Homo erectus populations in Africa, Europe, Asia, and Australia. Over this much time, each continent would have its own distinctive mitochondrial sequence. Much later, when Homo sapiens emerged out of Africa, we supposedly mated with Homo erectus derivatives (such as the Neanderthals and the Denisovans), giving ample opportunity for the addition of more Y chromosome and mitochondrial lines into the human population.

Some have argued that a consensus “Eve” sequence is expected to arise by chance, even if there was no literal “Eve,” based upon what is called “coalescence theory.” Trying to use coalescence theory to explain why all humans came from a single woman (who in their model was not the true Eve, but was a member of a large population), requires many unrealistic assumptions. Most importantly, global coalescence requires maintenance through deep time of a single unified breeding population with perfectly random mating. The coalescence calculation fails when given biologically realistic conditions where there are isolated sub-populations (tribes). The reality is that, historically, people have always spread out, distanced themselves from competing populations, sorted themselves into tribes, and preferentially mated within local populations. Obviously, people in Australia in ancient times were not normally mating with people in Africa. This means evolutionary coalescence cannot realistically be applied globally in terms of early mankind. In early human history, isolated tribes clearly diverged from each other, producing “race-like” differences, which would have resulted in the preservation of whatever mitochondrial diversity might have been present in the beginning. It is actually very unreasonable to expect a clear evolutionary Eve sequence, given what we know about human reproduction.

This leads us to a remarkable conclusion – A real woman, who lived less than 10,000 years ago, is the mother of all of humanity. We know her mtDNA sequence. Within each one of us is a slightly-mutated version of her original sequence. Evolutionists have chosen to call her Eve, to which we heartily agree.

Figure 1: A “divergence plot” of human mitochondrial diversity. The historical Eve consensus sequence sits at the center of over 830 modern human sequences. For each modern individual, the distance from the center (Eve’s sequence) is equal to the number of letter differences between that person and the historical Eve sequence. There are three concentric circles, with the thicker middle one representing the average divergence from the Eve sequence. The outer and inner circles represent plus or minus one standard deviation. People are on average only 22 mutations removed from Eve, but some are closer and some farther away, as expected from random mutation. Given the current mitochondrial mutation rate, this amount of mutational divergence from Eve would be expected to arise in just a few thousand years.

2. Genetic evidence that there was a literal Adam, the father of us all.

All parties now agree that there is only one paternal ancestor for all people on earth. As in the case of Mitochondrial Eve, many evolutionists regret that they coined the term “Y-Chromosome Adam,” and for this reason they now generally avoid the name Adam, calling him instead the “most recent common ancestor” (MRCA). Many of the same arguments that we outlined in the Mitochondrial Eve section above also apply to Y-chromosome Adam, so we will not restate them. Even though biblically the MRCA of all living men would be Noah, we will use the term Y-chromosome Adam instead because that is the term with which most people are familiar (Noah and Adam were only ten generations apart and so would have had Y chromosomes that were essentially identical).

Contrary to all evolutionary expectations, the uniqueness of the human Y chromosome has been confirmed by the recent re-sequencing of the chimpanzee Y chromosome. The original chimp genome (which was said to be 98% identical to human) had major problems. The whole chimp genome now desperately needed to be revised. It appears this has recently been done, but so far the new sequences are not fully available [4] - with the exception of the chimp Y chromosome. [5] Remarkably, the corrected chimp Y chromosome is not at all “nearly-identical” to the human Y chromosome (as was previously reported). In fact, it is radically different. The chimp Y chromosome is only half as long as the human Y chromosome, meaning there is less than 50% total similarity. The remainder of the chimp Y is only 70% similar to the corresponding part of the human Y chromosome (so total similarity is only about 40%). From an evolutionary perspective, to get this much divergence in just 6 million years would require an impossibly high mutation rate for the Y chromosome. The authors of that study claimed that the chimp/human difference is more like they would expect when comparing the genomes of humans versus birds. We need to realize that the hypothetical evolutionary common ancestor of humans and birds would have lived at least 300 million years ago. [6] Humans7 allegedly diverged from a chimp-like ancestor just 6 million years ago (50-fold less time). There is no possibility that this amount of genetic change could have occurred in such a short time. Also, because the human and chimpanzee Y chromosomes are so different, one cannot use chimpanzees as an “outgroup” in human ancestry studies. With no outgroup to “root” the evolutionary ancestral tree, a totally different picture of human history emerges.

We have used SNP (single nucleotide polymorphism or single letter variant) data to analyze the Y chromosomes of more than 1200 men from multiple modern human populations. [7] That analysis has allowed us to reconstruct the original Y-chromosome Adam sequence, just as we did with Mitochondrial Eve. The Y-chromosome Adam sequence has in turn allowed us to determine how many mutations separate modern men from Adam. Today, the Y chromosomes of most modern men are less than 500 mutations removed from Y-chromosome Adam (Figure 2). Out of about 30 million sequenced letters in the Y chromosome, this amounts to only 0.002% change from Adam to most modern men, and the most divergent Y chromosomes (found scattered at very low frequencies among isolated tribes in southern Africa) are still only 0.006% different from Y-chromosome Adam. If the Y chromosome mutates extremely rapidly (required by evolutionists to explain the vast differences between chimp and human Y chromosomes), how is it possible that all men have nearly identical Y chromosomes, and are so very similar to Y-chromosome Adam? Even if we assume a fairly low mutation rate for the Y chromosome (about 1 mutation per chromosome per generation), we would need less than 500 generations (less than ten thousand years) to accumulate the observed mutations. This is the most straightforward application of the ‘molecular clock’ concept. This amount of time is probably an underestimate, for there are multiple factors that can temporarily increase the mutation rate, and every mutation is an irreversible ‘click’ on the genetic ratchet. Ten thousand years is certainly in the ‘ballpark’ of what would be predicted by the biblical perspective. However given the actual observed mutation rate, in 100,000-200,000 years (the evolutionary Out-of-Africa model), we would expect about 100,000-200,000 mutational differences between modern men and Y-chromosome Adam – at least 10-20 fold more than what is actually seen.

The biblical timeframe fits perfectly with known human mutation rates and the observed divergence from the Adam sequence. But the evolutionary timeframe would create a great deal more Y-chromosome diversity than is actually seen. The evolutionist’s problems get much worse when they invoke an ultra-high mutation rate for the human Y chromosome, as necessitated by the new chimp/human sequence comparisons. This new data is showing that Y-chromosome Adam very consistently fits the biblical perspective and is not at all compatible with the evolutionary perspective.

We are drawn again to a remarkable conclusion: A real man, who lived less than 10,000 years ago, is the father of all of humanity. We know his Y chromosome sequence. Within each male alive today there is a slightly-mutated version of this original DNA sequence. Following the case of Mitochondrial Eve, evolutionists have chosen to call him Adam, to which we again heartily agree.

Figure 2: A “divergence plot” of human Y chromosome diversity. The historical Adam consensus sequence sits at the center of several hundred samples of modern men from diverse people groups. This plot is based on 18,692 SNPs from the HapMap dataset, with the SNPs chosen to reflect a significant percentage of human Y chromosome diversity. The There are three concentric circles, with the thicker middle circle representing the average number of mutations that separate these living individuals from the Y chromosome ancestor. The outer and inner circles represent plus or minus one standard deviation. Some men are closer and some farther away from Adam, as expected from random mutation. Given the current mutation rate for the Y-chromosome, this amount of mutational divergence from Adam would be expected to arise in less than 10 thousand years.

3. Molecular clocks now put Adam and Eve in the same period – and within a biblical timeframe.

The straightforward use of the molecular clock concept involves: 1) measuring the actual mutation rate for a given species’ genome (or for a given chromosome) 2) counting how many mutations have accumulated and 3) calculating how long the mutations must have been accumulating. There are two primary underlying assumptions: a) mutations accumulate at a constant rate b) most mutations are not under strong selection. When we (the authors) have followed this exact procedure using available mitochondrial data, we see that Mitochondrial Eve lived less than 6,000 years ago. [8] When we follow this same procedure using the Y chromosome data, we see that Y-chromosome Adam lived very roughly 6,000 years ago. [9] Since all dating methods are only approximate, we can safely say that both Mitochondrial Eve and Y-chromosome Adam lived in the same basic timeframe – and this timeframe is remarkably consistent with the most straightforward reading of the Bible.

Evolutionists do not employ a straightforward use of the molecular clock. They need to reject the actual observed mutation rates (which yield dates that they feel are much too recent), so instead they must use hypothetical rates that are roughly 10-20 fold lower than what is actually observed (yielding dates 10-20 fold older for both Adam and Eve). Dates for Adam and Eve that are based on evolutionary assumptions have been extremely inconsistent over the years, and have been under constant revision. For a long time evolutionists have been arguing that Mitochondrial Eve and Y-Chromosome Adam did not even live in the same timeframe and were separated by tens of thousands of years. However, evolutionists now widely agree that Mitochondrial Eve and Y-Chromosome Adam lived in the same basic timeframe. Poznik and colleagues affirm this in the journal Science (2013),

Applying equivalent methodologies to the Y chromosome and the mitochondrial genome, we estimate the time to the most recent common ancestor (TMRCA) of the Y chromosome to be 120 to 156 thousand years and the mitochondrial genome TMRCA to be 99 to 148 thousand years. Our findings suggest that, contrary to previous claims, male lineages do not coalesce significantly more recently than female lineages. [emphasis added] [10]

As we pointed out above, using realistic mutation rates (10-20 fold higher) would easily bring these dates into alignment with biblical history.

4. Human genetic uniformity shows there are no races: we are just one human race.

The genomes of many men and women from all over the world have now been sequenced. To the evolutionist’s general surprise, we are all very closely related. On average, the genomes of any two random people are 99.9% the identical. The few differences that are observed do not closely follow the artificial categories we call “races.” Using classical, but outmoded, ideas of race, two people from different “races” have almost the same percent difference as two people from the same “race.” Skin color is an extremely poor predictor of actual genetic relatedness, and so grouping people based on “racial categories” is no longer justifiable. Because the term “race” is no longer justified scientifically, the more meaningful terminology should be to categorize genetically-distinct human populations as “people groups”.

This was all a big surprise to the scientific community. First, it was expected that over deep time, any sizeable population should accumulate enormous numbers of mutations. So it was expected that mankind, having very deep roots, should have enormous genetic diversity. What was actually seen was that there is remarkably little human genetic diversity – much less diversity than is seen in most other mammals. Second, since the time of Darwin it has been thought that traditional racial distinctions (based primarily on skin color) reflected major genetic differences. It was thought that such differences could only have developed through random mutation and natural selection operating over a very long period of time. It was expected that the races would prove to be genetically very different, and it was thought that the evolution of the races must have happened over very deep time. The actual genetic evidence makes it clear that we are one race, and that we come from a narrow genetic base, that the source population lived quite recently, and that people groups diverged much more recently than previously thought.

All this is remarkably consistent with the biblical perspective, wherein: 1) humanity was derived from a single first couple not so long ago 2) there was genetic divergence of the people groups after the Tower of Babel dispersion (by clan/language/Y-chromosome), coming out of the Middle East 3) there was rapid formation of the world’s people groups, mediated by fragmentation (partitioning) of the genetic diversity that was already present in the human population and 4) Darwinian mutation/selection only played a very minor role in the establishment of today’s people groups.

From a biblical perspective there is no problem with a relatively homogeneous human population. We start with just two people (constituting an extreme, yet benign, “population bottleneck”), and then 10 generations later there is a second, single-generation bottleneck of just 8 people occurred at the time of Noah. Both bottlenecks were very brief (just one generation) and were followed by explosive growth, and in both cases there would be almost no previously accumulated mutations - hence no detrimental inbreeding effects. On the other hand, limited human genetic diversity and recent divergence of the people groups is obviously NOT compatible with the evolutionary perspective, and this has forced evolutionists into the story-telling mode – requiring a long series of far-fetched scenarios.

5. Most human genetic diversity could have easily been built into Adam and Eve’s genomes.

Although human beings are remarkably similar genetically, we still each have unique gifts and talents. We also each have our own unique set of harmful mutations. It is widely assumed that all human variation arose via random mutations – including all forms of beauty, all forms of genius, and all types of spiritual gifting. However, any thoughtful person should be able to see that these positive qualities cannot arise via random misspellings within the genome. The Bible teaches us that it is God who gives us these positive qualities (they are gifts). Rationally, this is the most reasonable explanation for these things. As we will show, most human genetic variation can be attributed to designed genetic diversity programmed into the genomes of Adam and Eve. Therefore, we can easily refute the new evolutionary argument that is coming from the theistic evolutionists, which claims that the level of genetic diversity seen in the human race today precludes a literal Adam and Eve.

Several well-known evangelical Christians have stated both in public and in print that Adam and Eve are genetically impossible. For example, Francis Collins has claimed, “There is no way you can develop this level of variation between us from one or two ancestors.” [11] His colleague, Dennis Venema, has said, “You would have to postulate that there's been this absolutely astronomical mutation rate that has produced all these new variants in an incredibly short period of time. Those types of mutation rates are just not possible. It would mutate us out of existence.” [12] These statements sound authoritative, but reflect a remarkably superficial consideration of the problem.

It is ironic that, on one hand, evolutionists resort to a recent and extreme genetic bottleneck to explain why there is so little diversity among humans, while on the other hand they claim there is too much diversity to permit a biblical Adam and Eve.

If Adam’s genome had been intelligently designed, it would obviously have been designed to include a great number of designed genetic variants (see Figures 3a and 3b). Otherwise all people would essentially be clones of Adam, which would be bad design for many obvious reasons. How much genetic variation could be designed into the genomes of Adam and Eve? The answer might seem surprising all known single-letter variants (SNPs) now present within the current human population could have been programmed into two diploid individuals. Together, Adam and Eve had four sets of chromosomes. Since there are only four genetic letters (A, T, C, G), Adam and Eve could have contained every single nucleotide polymorphism (SNP) now seen in the human race (i.e., every letter variant currently in the human race could have been pre-loaded into Adam and Eve’s four sets of chromosomes). Adam and Eve could easily have been heterozygous at 100 million nucleotide sites, but we do not need anything like this to explain modern human diversity. Even now a single person is heterozygous at roughly four million sites and carries a large part of all human variation. There are less than 15 million common SNPs found in all of humanity, [13] and a single modern couple could account for a very large part of all human variation (about 8 million SNPs). Since most common genetic variations are not associated with disease, most variation could very reasonably be attributed to designed variation.

What would prevent God from engineering 25 million variants (heterozygous sites) into Adam from the very beginning? If we assume Eve was assigned her own unique genome, this would double the amount of potential designed diversity. If that was not enough diversity, God could have created different genomes in each of Adam and Eve’s reproductive cells. There really is no limit to how much diversity God could have designed into Adam and Eve, but we do not need to invoke anything more than simple heterozygosity. Adam’s potential heterozygosity alone is sufficient to explain nearly all human genetic diversity. [14]

In addition to these common variations, there are many rare variations also found in the human genome, and these are generally restricted to specific people groups and limited geographic areas, meaning these must represent new mutations that have been added to the originally designed variations. These rare variations are routinely associated with genetic damage. [15] These would logically have arisen more recently in human history, by random mutation, after the Fall.

Even though many mutations have accumulated in the genome during human history, it is reasonable to conclude that most observable human genetic variation was created by God. The biblical perspective has unique explanatory power in terms of giving a credible explanation for the amazing range of human traits and abilities. There is no single “superior genotype”. We all have unique sets of gifts and talents, which very reasonably reflect good design, and for which we can give thanks to God.

Figure 3a and 3b: There would have been four original sets of chromosomes in Eden (two in Adam and two in Eve). Each set could have been unique (with Eve given her own genome), or Eve could have been a near-clone of Adam (two sets of chromosomes in duplicate). With four starting chromosome sets, at any given nucleotide site all four of the possible nucleotides could have been present (Figure 3a, three examples shown in red). However, nearly all diversity found in the human genome today is represented by bi-allelic positions (Figure 3b), where any given variant location has but two alternate letters. Because of the potential for inbreeding in the family lines of the passengers on the Ark, and because only eight people made it through the Flood, Eden could have easily contained much more genetic diversity than is now seen within the human population, regardless of whether Adam and Eve had their own unique genomes or Eve’s genome was nearly identical to Adam’s.

6. Genetic evidence for the partitioning (not the evolution) of human people groups.

The book of Genesis includes detailed genealogical records for Noah, his three sons, and subsequent patriarchs. From a biblical perspective, these patriarchs became the “fathers of the nations” (i.e., the main people groups). If these ancient records are true, we should see evidence of these patriarchs within the Y chromosome data we have available to us today. Our preliminary analysis suggests that within the major human Y chromosome haplotypes we do indeed see evidence for the biblical patriarchs who became the founders of tongues and nations.

Genesis chapter 10 has been called The Table of Nations. It lists the 16 grandsons of Noah and describes how they founded the diverging clans, which then became the nations and language groups of the early civilized world. Genesis 10 also approximates the regions into which these groups initially migrated after the Babel episode. For example, the Bible indicates that Japheth had 7 sons, Ham had 4, and Shem had 5. Japheth’s descendants mostly moved into Eurasia. Ham’s descendants lived in Mesopotamia, Western Asia (modern Turkey), the Levant (as the Canaanites), Arabia, and northern Africa. Shem’s descendants lived across the Middle East. Much time has elapsed since this historical information was recorded. People have migrated, wars have been fought, and massive civilizations have risen and fallen. Therefore we should not expect a 100% correlation between the Table of Nations and modern human populations or haplotypes (genetics). From a biblical perspective there should be clear evidences of correspondence between Genesis 10 and many distribution of many of the people groups and nations of today. This is indeed clearly seen. In addition, our preliminary analyses suggest that there is a similar correspondence between Genesis 10 and modern haplogroups which geneticists now observe globally (see Figure 4).

For example, the number of major branches in the human Y chromosome family tree (Figure 4) approximates the number of grandsons of Noah. It did not have to be this way. If the mutation rate was much lower, fewer branches would have been recorded. And if much warfare and/or population extinction had occurred, many branches would have gone extinct. Yet, the data indicate there was a massive and rapid expansion of the world population outside of Africa and that this expansion happened while all the Y chromosome lines in that population were only slightly diverged. The expansion was so rapid that most major lineages were preserved. The best way to preserve the many branches we see is through rapid population growth, for that necessitates less death and is a recipe for the capture of more rare genetic events. In evolutionary models, most lineages are eventually lost due to the winnowing effects of time. Evolutionary time produces “leggy” family trees (few branches). Rapid growth produces “bushy” family trees. Seeing a giant ‘starburst’ within the over-all pattern of human ancestry (Figure 4) is a major surprise to those who believed in deep time and requires them to do a major re-think.

A starburst pattern is exactly what we see in the haplogroups of Eurasian peoples: most lines go back to just a few founding ancestors that were just a few mutations away from each other (as if the founders of the many people groups were themselves extremely closely related). The African-specific branches also show evidence of expansion, but their branches are more “leggy” and thus there are fewer genetic lineages preserved. This is not evidence that African haplogroups are older, since all people groups have the same root (Y chromosome Adam), and so all haplogroups must be exactly the same age. The most leggy lines most likely arose from one of the branches of the Ham lineage. Since these African haplotypes are not any older than other groups, it is more reasonable to conclude these populations simply accumulated more mutations. This could happen for various reasons: a) their average generation times were shorter b) their historic population sizes had been lower c) they had a higher mutation rate (due to environmental or genetic factors) or d) a combination of all these factors. Lastly, these populations may not have multiplied as fast as those outside Africa, leading to more “leggy” (with less internal branches) family lineages.

Interestingly, the most distant outliers within today’s world population groups are the Khoi-San “click” speaking bushmen of southern Africa and the pygmies of the central rainforests. Both populations are assumed to be “old,” but they are small, isolated, and are best seen as highly divergent and unrepresentative outliers. The entire Out-of-Africa theory is framed around these rare outliers who clearly have atypical histories. Why should we trust this model or focus on rare outlier datapoints? If all men come from Adam, then all human lineages are equally old. Therefore, the more divergent populations must have undergone more change in the same amount of time.

Figure 4: A Human Y-chromosome “family tree” (modified from Hallast et al., 2015) [16] . The letters represent the known major Y chromosome groups (“haplogroups”) which are found within living men. Our preliminary evidence suggests that at the base of each line that connects to a haplogroup is a specific historical figure – most being likely biblical patriarchs described in the book of Genesis (such as the 16 grandsons of Noah who were called the fathers of the nations – Genesis 10). The branch lengths are proportional to the average number of mutations that separate the sequences of living people from the base of each branch or branches. As can be seen, most Y chromosome lineages in the world fall into three large groups (blue, green, and red), and these three large groups trace back to three very closely related men. This “starburst” pattern is best explained by rapid population growth starting from a very small population of very closely-related patriarchs, as anticipated by the book of Genesis. We have color-coded the branches according to our current understanding of the lines descending from Shem (blue), Ham (red), and Japheth (green). Group J includes many living Jews who claim to be part of the Cohanim (priests) and thus descended from Shem through Abraham and then through Aaron. The three closely related males that gave rise to all the major haplogroups seen today, may actually be the three sons of Noah, in which case the Y chromosome of Noah would be very close to his sons (very near the intersection of the three colors), and Adam’s sequence would be nearly identical to that of Noah. The different lengths of the lines seen in this tree reflect people groups that presumably experienced different rates of divergence from the ancestral sequences. This will be addressed in a separate publication. [16]

7. Biological evidence affirms the genealogies from Adam to Moses, and reflects genetic degeneration.

The Bible records detailed genealogies, which appear to be complete, and go from Adam to Jesus. The Bible also records the age of the patriarchs at the time they fathered their son, and their age at the time of death. More specifically, the Bible gives us the age of death of the first 23 generations, from Adam to Moses. [17] , [18] Many of those people who have trouble believing in a literal Adam and Eve also have trouble believing the biblical genealogies and the ages of death of the patriarchs. Yet when we plot the age of death of the patriarchs, we see a very striking pattern (see Figure 5). The earliest patriarchs lived to be incredibly old, but from the time of Noah onward lifespans decreased rapidly and systematically following a biological decay curve. What could possibly explain this?

The most reasonable explanation for the pattern seen in Figure 5 is that there has been continuous and systematic genetic degeneration since the time of Adam and Eve. This is not only consistent with the basic message of the Bible, but is supported by a great deal of modern genetic evidence. There is growing scientific evidence that the human genome is rapidly degenerating due to mutation accumulation. The book entitled “Genetic Entropy,” by one of the authors, summarizes the diverse scientific evidences indicating long-term human genetic degeneration. This is supported by papers by several world-famous population geneticists such as Crow (1997) [19] , and Lynch (2010). [20] It is also supported by genetic theory, numerical simulation experiments, and numerous other scientific publications. [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29]

The fact that humanity is genetically degenerating due to mutation accumulation amounts to “evolution going backwards.” This is the anti-thesis of modern Darwinian thought. Remarkably, such degeneration is very consistent with the Bible. In many places, the Bible indicates that we are dying people in a dying world (figure 6), and that creation itself is wearing out (Psa 39:5&11 Psa 102:25-26 Mat 24:35 Ro 8:22 Heb 1:10-12 1Pe 1:24-25).

The most obvious outward evidences for genetic degeneration are aging, death, and shortened lifespans. The degeneration of man is explicitly recorded in the words of Jacob, who said to the Pharaoh “I have traveled this earth for 130 hard years. But my life has been short compared to the lives of my ancestors” (Genesis 47:9, NLT). The extreme longevity of the early patriarchs is very well documented in Genesis, Exodus, Numbers, Deuteronomy, and Joshua.

Figure 5: When biblical life spans are plotted against the number of generations since Noah, we see an amazing and systematic decline in life expectancy. The pattern of decline reveals a very clear biological decay curve. Fitting the data to the “line of best fit” reveals an exponential-type curve. The curve fits the data very well, with a coefficient of determination (R 2 ) of 0.96 (1.0 would be a perfect fit). See table 1 (reference below) to learn the specific patriarchs and their ages. The last data point shown is the average life expectancy (45 years) during the time of the Roman Empire (see This statistic excludes childhood deaths before age 10. From Roman times until recent advances in nutrition and medicine, human life expectancy has hovered in this range of 30-50 years (depending on variables such as childhood mortality). It seems highly unlikely that this biblical data could have resulted from an ancient fabrication. The curve is very consistent with the concept of genomic degeneration caused by mutation accumulation. The curve is very similar to the theoretical curves shown in Figures 4, 10a, 10b, 14, and the biological data in Figure 15 in the book “Genetic Entropy.” For more information on this analysis of the patriarchs and their ages see article entitled “Genetic Entropy Recorded in the Bible?”[30]

We do not normally think of the Bible as a source of scientific data. However, the recorded ages of the patriarchs do in fact constitute real data, which can be analyzed scientifically. Numerous scholars have done this. [31] We likewise have done this – going a bit further than previous analyses (see Table 1 in article). [32]

The plot shown in Figure 5 is telling us that the biblical data itself is not allegory or myth, but is real historical data. The data is coherent and internally consistent in a way that could never happen by chance. This is in spite of the fact that the data was drawn from various books of the Bible which were written by different authors at different times. Anyone who has studied biological data can see how very “tight” the data is – meaning the data points diverge very little from the trendline. The smooth curve is shaped according to the specific formula shown (y = 1064.7x -0.766 ). The R 2 statistic given above the plot is called the coefficient of determination, which tells us how well the data can be explained by the mathematical formula. The value seen for the Masoretic text (R 2 = 0.96), is extremely high – meaning that the shape of the trendline (the smooth curve) explains 96% of the variation in the lifespan data. Another way to say this is that the lifespans are declining in a mathematically precise manner.

Some unbelievers will claim that the mathematical nature of this decline arose because all these data points, scattered in various books of the Old Testament, were fabricated by a sophisticated and scheming person in a latter era. But such a person would need to be a skilled mathematician. Moreover, he or she would need to be driven by the malevolent ambition of deceiving the world into believing that, since the time of Noah, human fitness has been undergoing a very dramatic and very specific decay process. A much more reasonable explanation for this data would be that the mathematical nature of the declining lifespans arose because the biblical accounts are true, and are actually faithfully recording the historical unfolding of some fundamental natural degenerative process. We must reject the absurd idea that an ancient mathematician would have been able to fabricate or corrupt so many parts of the Old Testament, just so he could fool the world into believing that this very particular pattern of degeneration happened. If the Old Testament was written to deceive, why would the perpetrator fabricate such hard-to-believe data about people who lived to such great ages? How would that be convincing to anyone? Without the modern ability to analyze this type of data, and without any knowledge of genetic mutations, the decay curve (only seen clearly when the data are carefully plotted), would mean nothing to any of the early readers of the Bible. This forces us to accept the alternative explanation (as remarkable as it may seem), which is that the reported decline of lifespans arose because it was true, and because the relevant biblical accounts and genealogies were historically true.

The shape of the downward slope should be immediately recognized by any biologist. It is a biological decay curve. Noah’s descendants were undergoing some type of rapid degenerative process. As stated in the introduction, there is now very strong evidence that man is degenerating genetically (and has been going on for thousands of years), due to continuously accumulating mutations. This makes it very reasonable to conclude that the systematic degeneration of man that as documented in the Bible was due to mutation accumulation and resultant increase in “genetic entropy”. Indeed, biologically realistic numerical simulations (see Figure 6), show that given our current mutation rate (about 100 new mutations per person per generation), human fitness and longevity should have historically followed a decay curve very similar to the biblically-recorded decline in life expectancies. However, the extremely precipitous decline in lifespans recorded in the Bible, just after the Flood (Figure 5), is actually significantly steeper than our numerical simulations would have predicted. We have reasons to believe that the Flood was a high-radiation event, and that in the centuries immediately after the Flood, mutation rates may have been substantially higher than present.

Figure 6: Mutation accumulation over 200 generations, within a biologically realistic human population of 10,000 individuals and a realistic mutation rate of 100 per generation, as simulated using the computer program “Mendel’s Accountant”(see This program is a comprehensive numerical simulation program that tracks deleterious (harmful) mutations as they accumulate in a population even in the presence strong natural selection. As can be seen, mutations accumulate continuously and fitness declines continuously. In this timeframe fitness declined over 80%. The result is a classic biological decay curve – very similar to the decay curve based upon the biblical longevity data (see Figure 5). . Natural selection eliminated the “less fit” half of the population’s offspring every generation. The blue line represents population size – which in this experiment was held constant from one generation to the next. The shaded region represents the standard deviation (variation) within the population.

The lifespan data strongly supports the historicity and veracity of the Bible, and in particular, the book of Genesis. Likewise, the biblical data strongly indicates that the emerging scientific evidences of genetic degeneration in man are correct, and that genetic entropy is very real. Genetic entropy is the antithesis of evolution and powerfully speaks of the biblical Fall (Figure 7). All of this points to the desperate need for the redemption of mankind and all of creation.

Human genetic degeneration is remarkably consistent with the biblical perspective, with describes a perfect, created couple, a literal Fall, a decaying human population, and a world which is now “wearing out like a garment” (Heb 1:11).

Figure 7: We are dying people in a dying world, reaching out to the healing hand of God.

Part I Conclusion

Adam and Eve do not just represent the genetic foundation of the human race. Prior to their Fall, Adam and Eve were God’s model for marriage and spiritual fidelity. Originally, there were three in Eden – Adam, Eve, and their Creator-Lord who walked and talked with them in the garden. This is a picture of the Christian triune marriage – God, Husband, and Wife. Adam and Eve were without sin, were very close to God, were obedient to Him, and were under His protection and grace.

The Biblical perspective is that family has a sacred foundation, which is foundational to Christian faith. The evolutionary perceptive is that family is merely utilitarian – the best family structure is whatever helps propagate the species. Much of the western world is now abandoning the sacred view of family and marriage and is embracing the evolutionary perspective. This includes much of western Christianity, which is turning from the sacred biblical view and is embracing the evolutionary view. There is a strong correspondence between holding an evolutionary view of man and family, and embracing the sexual revolution, abortion, and compromise on all other moral issues. Which way will Catholic Church leaders go?

For over 150 years evolutionists have very aggressively attacked biblical authority and biblical historicity, arguing that the biblical perspective is ignorant and unscientific. As summarized above, there is now good science that is validating the biblical view. In part 2 of this paper we will go on to show that good science is now also strongly undermining the evolutionary perspective. But science cannot give a perfectly clear picture of ancient history – both sides will always be able raise up their own line of argumentation. The Church must make a moral decision. The Church cannot in good faith surrender these foundational issues to the currently reigning scientific consensus, which is ever-changing and is at present clearly becoming increasingly hostile to God.

The Church has a choice to make. Will the Church hold firm to the clear teachings of Holy Scripture and 2000 years of Church Tradition, or will the Church follow the lead of evolutionists – most of whom are hostile to the Bible, the Church, and Christ? Will Church leaders believe and follow God? Or will they believe and follow today’s popular human authorities? In the end, the question is not a technical issue, but a moral issue. If has to do with fidelity. To Whom will we give our allegiance? Whom will we serve?

“Now fear the Lord and serve him with all faithfulness. Throw away the gods your ancestors worshiped beyond the Euphrates River and in Egypt, and serve the Lord . But if serving the Lord seems undesirable to you, then choose for yourselves this day whom you will serve, whether the gods your ancestors served beyond the Euphrates, or the gods of the Amorites, in whose land you are living. But as for me and my household, we will serve the Lord .” Joshua 24:14-15 (NIV).

Genetic Evidences Refuting the Evolution of Man and Family


Scripture and Catholic Tradition clearly preclude evolution. The Bible indicates that there was no death before the Fall (Genesis 1:30, Genesis 2:17, Genesis 3:17-20 Romans 5:12), which clearly precludes the evolution of man. In all of Scripture there is no hint that God created anything via evolution, or that one basic kind of life could ever naturally morph into a fundamentally different form of life. The Bible makes it clear that each created “kind” reproduces according to its kind (Genesis 1:12-25). The Bible also makes it clear that Adam was made supernaturally from dust, and Eve was made supernaturally from Adam. As Fr. Thomas Hickey demonstrates elsewhere in these proceedings, these things have been foundational doctrines of the Church for nearly 2,000 years.

There is no question that the greatest atheist-maker of all time was Charles Darwin, who explicitly rejected Jesus Christ as well as “the sacred history of Genesis.” Because of Darwin, evolution is regularly held up as the antithesis to Christ in all parts of the world. The evolutionary perspective not only claims that natural selection created mankind from a chimp-like ape, but also that natural selection created the human family from the a chimp-like family structure. If we reject the biblical view of family that involves the triune model of marriage (God, Man, and Wife), then we must accept the idea that the human family is merely an extension of the chimp family, modified slightly by natural selection. Although chimpanzees are social animals and can play and show some sort of affection, the chimpanzee “family” has many disturbing characteristics.

The chimpanzee “family” is essentially “the group” (troop). There is no nuclear family unit such as father/mother/child. Sexual interactions within the troop are generally public and fleeting – lasting only a moment. Sexual interactions are nearly random, although they sometimes involve limited social significance, as well as some pecking-order (hierarchical) preferences. Chimpanzee sexual interactions appear to have minimal significance beyond a very brief moment of physical stimulation. A receptive female will often be mating with multiple males almost simultaneously, such that there is no way for a father to identify his own offspring. Male commitment to a female is not generally observed. Males take minimal interest in offspring. Sexual interactions are quite arbitrary and can be heterosexual, homosexual, or incestuous. The female usually has a lasting bond with the offspring that she nurses, but if a child dies she quickly abandons the corpse. Murder and cannibalism of children are sometimes seen, indicating the apes, like humans, are fallen. Should we use the chimp family as a model for the human family? This is a serious question with profound social and spiritual significance.

It is generally thought that the human family was derived from the chimp family via natural selection. Survival of the fittest (more accurately failure of the less fit to reproduce) is said to have allowed the evolution of our stronger feelings of love and commitment (which now appear to be waning). If natural selection produced human love and commitment, then we must ask, “Are we now devolving back into the chimpanzee family structure?” If natural selection is what produced human love and commitment, then isn’t sacrificial, faithful, agape love merely an evolutionary reflex – with no spiritual or moral basis? This perspective suggests that both love and the human family are just relics of previous evolutionary forces, and the human family will be subject to further evolutionary modifications as pragmatism and natural selection demand.

This very dark view of love and family is entirely consistent with the moral character of evolutionary thinking. At its very core, the evolutionary perspective requires systematic destruction of the less fit. Is this God’s way of creating? The reason a population surplus is always essential for natural selection to operate is because death is the fundamental driving force underlying natural selection. Death is the friend of evolution. As Carl Sagan once said,

The secrets of evolution are death and time—the deaths of enormous numbers of lifeforms that were imperfectly adapted to the environment and time for a long succession of small mutations. [33]

But the biblical view is that death is the ultimate enemy (“The last enemy to be destroyed is death” – 1Cor 15:26). Death is overcome by Christ on the cross (2Ti 1:10 1Cor 15:54-57), and is something that will someday be cast into the lake of fire (Rev 20:6 Rev 20:14 Rev 21:4). The biblical view is that systematic death is NOT the way God created, and in fact death is alien to God’s creation. There was no death in God’s “very good” creation before the Fall (Genesis 1:30-31, Genesis 2:17, Romans 5:12).

Too much credence has been assigned to the people who developed and now promote the case for ape-to-man evolution. As we will see, the ape-to-man story arose as a systematically developed mental construction – without basis in reality. It is not a coincidence that the principal “human authorities” who created the evolutionary story consistently were people who either openly or covertly made themselves enemies of God, the Bible, and Christian values. Yet these same people have been idolized and treated as demigods by most universities, governments, and all the major media outlets. Even some prominent Christian leaders have come to worship these men. But these famous men were just as fallible as you and I. The new scientific evidence emerging in the 21st century is showing that these “great men” were consistently wrong. They were smart people who were blinded by their ideological commitments and the reigning group-think of their day.

By God’s grace, 21st century genetics is strongly affirming Scripture and refuting evolutionary stories. Remarkably, when we examine the nature of the genome and the genetic make-up of modern human populations, we find strong genetic evidence that precludes ape-to-man evolution. Below we will outline seven genetic lines of evidence that make human evolution impossible.

1. Mutations could not create mankind, and cannot explain mankind’s unique attributes.

While humans have some notable similarities to apes, in the most important respects mankind is utterly unique. Only humans can do scientific research, sequence their own genome, reason, engineer cities, visit the moon, write books/programs/poetry/music, or show agape love. We clearly have dominion over the earth. Only man is a conscious moral being with a soul, capable of communion with God. In all these respects we are incredibly unique. As evolutionist Juan Arsuaga writes in The Neanderthal’s Necklace:

We are unique and alone now in the world. There is no other animal species that truly resembles our own. A physical and mental chasm separates us from all other living creatures. There is no other bipedal mammal. No other mammal controls and uses fire, writes books, travels in space, paints portraits, or prays. This is not a question of degrees. It is all or nothing there is no semi-bipedal animal, none that makes only small fires, writes only short sentences, builds only rudimentary spaceships, draws just a little bit, or prays just occasionally. [34]

Likewise, in the words of a famous evolutionist, Jacob Bronowski:

Man is a singular creature. He has a set of gifts which make him unique among the animals: so that, unlike them, he is not a figure in the landscape – he is a shaper of the landscape. [35]

Most importantly, the essential biblical difference between ape and man is that man was created in the image of God, and God’s Spirit was breathed into man (Genesis 1:27, Genesis 2:7 - see Figure1). In this light, it is extremely important that we acknowledge that we are not just another primate species. Rather, in a taxonomic sense mankind should most accurately be placed in a separate kingdom (i.e., as in plant kingdom, animal kingdom, and human kingdom). Evolutionists cannot even begin to explain how mutation/selection might have created consciousness, intelligence, moral accountability, or a soul. We are NOT part of an evolutionary continuum. We clearly have a spark of the divine is us. This is not a subject of debate among Christians. However, this reality is strongly discordant with the evolutionary worldview.

The evolutionary view is that the human mind and soul emerged via a series of random mutations filtered by natural selection. Mutations are essentially random word-processing errors that arise during the replication of our genes, and our genes are essentially executable programs that act as the instruction manual for human life. Executable programs simply do not arise from word-processing errors.

From a genetic point of view, the genes that enable our unique capabilities, gifts, and talents (i.e., science, art, love, relation to God) could not arise by any series of random typographical mistakes filtered by natural selection – not in any amount of time. Our unique human qualities are simply not “evolvable.” This is NOT how programs and instruction manuals arise. There is no credible biological mechanism that could lead to the spontaneous origin of mind, consciousness, intelligence, soul, or spirit. While these human traits are found within a biological context (i.e., within an animal-like body/brain), they clearly transcend mere biology. We are exquisitely programmed to be more than animals, and our bodies are well-designed vessels that house our immaterial being: mind, soul, and spirit. All this is most compatible with the biblical perspective of mankind: a) we are fearfully and wonderfully made (Psalm 139:14) b) we are made in the image of God (Gen 1:27 9:6) and c) God breathed His spirit into us (Gen 2:7).

Figure 1: Mankind is unique. We alone have responsibility (dominion)
over the earth.

2. The genetic chasm between chimp and man is vast.

“We are 98-99% identical to chimpanzee.” This paradigm has clearly been falsified, but sadly the public has not been told. The long-standing claim that the human and chimpanzee genomes are almost identical was largely based upon selective use of data and was driven by ideological commitment. During the last decade new evidence has falsified this destructive dogma. Sadly, even while the evidence supporting the claim of 98-99% genetic identity has collapsed, the textbooks and media still parrot the mantra and the correct numbers are essentially never heard within the public realm. In 2002 it was shown that human-chimp similarity was less than 95%. [36] More recently, in the Proceedings of the National Academy of Sciences in 2012, primate evolutionist Todd Preuss states,

It is now clear that the genetic differences between humans and chimpanzees are far more extensive than previously thought their genomes are not 98% or 99% identical. [37]

It turns out the actual genetic difference between human and chimpanzees were greatly underestimated. In a paper published in Nature in 2010 it was shown that the Y chromosomes of human/chimp were less than 70% identical (Hughes, 2010). The authors of that paper concluded the human/chimp Y chromosome differences were as great as the differences they expected between humans and birds!

Indeed, at 6 million years of separation, the difference in MSY gene content [the male specific region of the Y chromosome] in chimpanzee and human is more comparable to the difference in autosomal gene content in chicken and human, at 310 million years of separation. [38]

Most significantly, recent work by Tomkins and Bergman has validated and extended the “70%” discovery, showing that all chimp/human homologous chromosomes have similarities in the approximate range of about 70% (Figure 2). [39] , [40] The profound differences between the human and chimp genomes will be shown to be even greater, once the chimp genome is re-sequenced. The chimp genome was assembled using the human genome as a template, which greatly biased the assembly and excluded perhaps 10% of the most divergent chimp sequences. Cohen speaks of this in Scientific American, raising criticisms against the Chimpanzee Sequencing and Analysis Consortium. He refers to human and chimp DNA identity claims as “The Myth of 1%” – the title of his article. [41]

How did the 98-99% dogma get established? Ideological commitments led to bad science and bad science writing. The 98-99% mantra was driven by the desire to indoctrinate, rather than a desire to discover. We urge Christian thought-leaders to remember that scientists are not always objective, and that many times entire branches of science can be seriously distorted by ideologically-driven agendas.

Why does 98% vs. 70% matter? First, it matters because it shows that humans and chimps are definitely not “nearly identical.” Yes, we have similar body plans, eat similar foods, and have similar temperature requirements, etc., but we are profoundly different genetically. This is partly why humans have vastly superior capabilities and characteristics. A 30% genomic difference between humans and chimps represents about one billion genetic letter differences. This represents a vast amount of new information (which is logically required for the creation of the biological framework/context for the human mind/soul/spirit). This vast amount of new information could never have arisen by Darwinian trial and error process – not in any amount of time. This is verifiable on many scientific levels. For example, as far back as the 1950s, evolutionary mathematicians realized there was a huge problem. There were simply not enough beneficial mutations, or enough time, to create the profound genetic differences between ape and man. Modern discoveries have made these mathematical difficulties orders of magnitude worse. The reason evolutionists were so strongly committed to just a 2% difference between man and chimp was because larger differences would make the evolutionary story of common descent impossible. The collapse of the 98-99% identity paradigm discredits the evolutionary explanation for human origins.

Figure 2: Geneticist Jeff Tomkins has analyzed the percent of human-chimp DNA sequence alignment using optimized sequence slices sorted by chromosome. Across all chromosomes the average percent similarity is only about 70%. The percent difference has gone from about 2% to about 30%. Thus, the actual difference is 15-fold greater than previously claimed.

3. The insurmountable waiting time problem.

New research now shows that there is an insurmountable waiting time problem associated with the human evolution story. [42] To change an ape to a man would require an enormous amount of re-programming (lots of new instructions for the genetic instruction manual). This large amount of new information is equivalent to a large number of books. Coherent, constructive information must somehow come together, in a way that involves tens of millions of very specific letter changes (mutations), and these letter changes must combine to creates millions of specific “words” (i.e., short strings of genetic letters), and these words must make sense within the context an enormous number of sentences (i.e., genetic elements), paragraphs (i.e., genetic introns), and chapters (i.e., genes). Without any type of intelligence, it is simply not credible that such extensive reprogramming, and the creation of so much new information, could arise by the trial and error process of random mutations plus natural selection. But this is exactly what evolutionary theory requires.

Most rational people can immediately see that books, instruction manuals, and executable programs could never arise spontaneously apart from some type of intelligent author or programmer. But let us suppose that programs actually could arise spontaneously without programmers, via the trial and error process of random mutations and natural selection. How long would it take to accomplish this? Let us not ask how long it might take to establish tens of millions of genetic letter changes that are minimally required for the ape-to-man scenario. Rather, let us just ask how long it would take to establish 8 genetic letter changes (i.e., just changing a specific DNA sequence like AAAAAAAA to the alternative sequence TCGTCGTC). This is very similar to creating a single new word in a book. Evolution requires the discovery of specific new biochemical pathways and these require specific solutions to specific puzzles. In fact, millions of such solutions must have been found in any ape-to-man evolutionary scenario. Any one of these would have been much more complicated than just changing a specific string of 8 letters into a specific string of 8 different letters.

We can actually approximate the waiting time for creating and establishing a string of 8 specific mutations in a particular genomic location in a pre-human population. We can do this because we know the human mutation rate, we know the size of the hypothetical population of apes that gradually morphed into human beings, and we know how natural selection actually works.

Using a scientific methodology called comprehensive numerical simulation, we have been able to directly test the severity of the “waiting time problem” for a pre-human population. The waiting time required to create a word of 8 specific letters (nucleotides) is astounding. Regardless of whether one uses very sophisticated numerical simulations as we did, or one uses mathematical approximations, the results are very similar. The results make human evolution utterly impossible. Even given ideal conditions, it takes over 18 billion years to create and permanently establish (in population genetic terms, “fix”), a specific string of 8 genetic letters in a hypothetical pre-human population. There is not enough time to even establish a string of 8 letters, not even in the timeframe of the big bang (said to be 13.7 billion years ago). Yet such a string would be just a drop in the ocean of new information needed to transform an ape into a man. So in this light, how could tens of million of beneficial letter changes be established within the human genome, during the short time that it took an ape species to evolve into mankind? Human evolution is said to have happened just during the last 6 million years. This is 3,000-fold less time than is required to establish a single word of just 8 letters!

Although mutations are arising in the human genome all the time (because the genome is so large and because the rate is about 100 new mutations per person per generation), it takes a remarkably long time for a specific nucleotide (letter), at a specific location, to mutation into a specific alternative letter (happening only once in 100 million tries). To get a specific string of 8 specific mutations takes vastly more time. And the correct letter string must arise many times before it “catches hold,” so that it can eventually be amplified by natural selection and hence spread throughout the whole population and become established (“fixed”).

Leading evolutionary scientists have acknowledged that waiting time is a very real problem for any pre-human population, and have published computations showing even longer waiting times than we observed, when modeling comparable scenarios. [43] For example, Durrett and Schmidt in The Annals of Applied Probability show that the average waiting time for 8 specifically placed mutations in a pre-human population is on the order of 650 million years. But this estimate is just “time to first instance.” When accounting for random loss due to a well-established principle known as “genetic drift,” they acknowledge the actual waiting time should be about 100-fold longer. They say: “In reality the probability of fixation is approximately the selective advantage conferred by the mutation s and even for strongly beneficial mutations we have s ≤ 0.01. This means that the mutation would need to arise more than 100 times in order to achieve fixation…” [44] In their calculations they assume a fitness benefit of 1% which means the 8 nucleotide sequence would have to arise again and again, at least 100 times over, before it can finally “catch hold” in the population. So their calculations indicate that the true waiting time to fixation would be roughly 65 billion years. This is four times the age of the universe (assuming a big bang singularity 13.7 billion years ago).

After years of doing numerical simulation research, we have found that it is impossible to achieve any significant forward evolution (net gain) in any biologically realistic human-type population. [45] , [46] , [47] The closest we can come to forward evolution is the establishment of a few isolated beneficial mutations, resulting in some limited amount of adaptation to a special environment or circumstance. Obviously, this cannot explain how either mankind or the human genome arose. Moreover, even when a few beneficial mutations can cause adaptation, accumulating deleterious (harmful) mutations (which collect in much higher numbers) preclude any net gain in information (see next section).

Contrary to popular thinking, natural selection is not really a creative force, but is a mechanism that slows degeneration. Arguably, natural selection is part of God’s design for the post-Fall world. Selection slows down degeneration and allows a limited amount of fine-tuning in terms of adaptation to new environments. From a biblical perspective, this is part of God’s post-Fall economy, allowing for both the “filling” of all parts of the earth (adaptation), and allowing time for the unfolding of God’s redemptive plan (slower degeneration). All this is consistent with the biblical perspective, while powerfully refuting evolution.

4. Humanity has been degenerating ever since the Fall.

Every time a human cell divides, a few new mutations arise. These mutations are, very literally, copying errors in the instruction book of life. Such errors are consistently destructive – they systematically reduce the information content of the genome. Almost all bad mutations must be removed over time in order to make forward evolution even remotely feasible. Yet leading human geneticists agree that in modern man deleterious (harmful) mutations vastly outnumber any rare beneficial mutations. Such deleterious mutations are accumulating much faster than they can be selected away (removed from the “gene pool” by natural selection), and so the human genome is presently degenerating. The accumulation of extremely numerous harmful mutations destroys genetic information much faster than rare beneficial mutations can possibly create new information. It is acknowledged by many scientists that that this degenerative process has been going on throughout recorded history. Numerous leading evolutionists like Crow, [48] Kondrashov, [49] and Lynch, [50] among others, have published work validating the reality of this profound problem.

Obviously, random changes in an instruction manual will almost always be harmful and will systematically destroy essential information. But a typical copying error (mutation) will have only a trivial effect all by itself (changing just one letter out of three billion letters). Yet the continuous accumulation of millions of these tiny mistakes in our genomes over generational time must eventually become lethal. To prevent our species from genetic degeneration and eventual extinction requires that essentially all mutational errors somehow be identified and removed.

We, along with other collaborating scientists, have studied the problem of harmful mutation accumulation in great depth, going deeper than anyone before us. We agree with the current assessment that the human genome is degenerating, but we are convinced the problem is much worse than is generally acknowledged. The theoretical basis for this is described in depth in the book Genetic Entropy. [51] In addition, we, along with our collaborators, have produced a long series of published scientific papers, which show experimental evidence of pervasive and systematic genetic degeneration. These papers employ a form of scientific analysis called “numerical simulation,” and they show that when given realistic circumstances, over 90% of harmful mutations fail to be selected away, even with intense natural selection. [52] , [53] , [54] , [55] , [56] , [57] , [58] Lastly, we have carefully documented the reality of genetic entropy in living biological systems such as the influenza virus, [59] human mitochondria, [60] and long-term E. coli populations. [61] The case for human genetic degeneration is compelling on the scientific level. The most fundamental reason why most harmful mutations are not removed over time is because most such mutations are extremely subtle in their biological effect (they are technically called “nearly-neutral”), and so they are invisible to natural selection. A second basic problem is that mutations in the human genome are occurring at an alarmingly high rate – much faster than they can conceivably be selected away.

In addition to these many scientific evidences, there is strong historical evidence, as recorded in the Bible, which indicates that man is degenerating. See part one of this paper (same volume), describing the biblical evidence for the devolution of man.

Diverse lines of evidence for human genetic degeneration indicate that the ape-to-man scenario is impossible, because the direction of net change is consistently downward, with the net effect never being upward. Human genetic degeneration is remarkably consistent with the biblical perspective, which describes a perfect created couple, a literal Fall, a decaying human population, and a world which is now “wearing out like a garment” (Heb 1:11).

Figure 3: Like rust on a car, deleterious (mildly harmful) mutations are slowly but continuously accumulating in the genome of all living creatures resulting in the erosion of genetic information over time. We see this in our own bodies as we age, and we see it happening in populations from generation to generation. This is one of the tragic consequences of man’s sin and the Fall recorded in Genesis chapter 3.

5. The rise and fall of “junk DNA”

Dr. Susumu Ohno coined the term “junk DNA” in 1972. [62] He argued that the human genome must be almost entirely non-functional junk because if most of the genome were actually functional, the rate of harmful mutations would be much too high, which would lead to genetic degeneration (de-evolution). Preceding Dr. Ohno, Dr. Kimura had developed his famous “neutral theory of evolution,” [63] which similarly claimed that most of the human genome was non-functional junk. Again, Kimura’s argument was primarily based on the realization that evolutionary theory could only establish and maintain a limited number of functional nucleotides. In both cases, the reason for invoking a genome that was mostly junk was because it was a necessary rescue mechanism for resolving fundamental problems with evolutionary theory. When Kimura published his views of neutral (functionless) evolution, most evolutionists were initially upset, feeling his theory was heretical. But he was able to eventually persuade them that his model was essential for rescuing neo-Darwinian theory from fatal internal problems.

Although the doctrine of pervasive junk DNA was developed as a rescue mechanism, it soon became very useful for evolutionary argumentation. It was said that our genome is littered with “junk,” and that this was consistent with the evolution of the human genome apart from any type of intelligent design. A junk-filled genome was used to argue against God as the author of the genome (there is no “Author of Life” needed to create a junky-genome). Furthermore, such junk DNA would be free to accumulate neutral mutations at a steady rate, creating a type of molecular clock, which could be used for mapping theoretical mileposts for evolutionary history. So junk DNA, neutral evolution, and the molecular clock became the new foundations for modern evolutionary theory. It seemed reasonable that since there really wasn’t very much useful information in the genome, selection only needed to create and maintain small portion (only about 2%) of the genome. The assumption that 98% of the genome was just junk became a popular “proof” that the human genome arose via haphazard evolution.

Junk DNA theory reigned supreme in academia for nearly 40 years. However, soon after the Human Genome Project was completed, Darwinian theory took a major hit. This happened because “phase two” of the genome project was the ENCODE Project – a multi-million dollar, international study tasked with determining how much of the genome was active. The 400+ ENCODE scientists discovered that most of the human genome, even the so-called “junk” DNA that is not translated into protein, is actually used (is actively transcribed into RNA). [64] A typical DNA letter within any gene is actually part of several different RNA transcripts, meaning any single random letter change in the “junk” DNA can affect multiple independent cellular processes. It was found that while we have only

22,000 human genes, those genes encode for several hundred thousand different human proteins. It turns out that different parts of a gene can be used for building many different proteins, so any gene is composed of multi-purpose building blocks. This requires a complex “splicing code,” and that code is within what was once called “junk” DNA. [65] The ENCODE results have completely changed the way we view the genome. Instead of it being just a protein-generating engine, the genome can now be seen as an RNA computer, doing multiple calculations, primarily within the so-called “junk” regions of the genome. Proteins can be seen as simply “output” from the nucleic acid computing systems. Also, within any given stretch of human DNA there are multiple overlapping codes, meaning that a change to any specific letter might affect multiple different genetic messages. Darwinian evolution simply cannot account for the origin or preservation of these overlapping codes.

Mainstream science (the ENCODE project and a wealth of data published over the last decade) has falsified the myth that almost all of the genome is “junk”. When the latest ENCODE results were published in a series of papers in 2012, a Science Magazine article headlined: “ENCODE Project Writes Eulogy for Junk DNA”. [66] Tom Gingeras, a senior scientist with ENCODE affirms this noting:

Almost every nucleotide [genetic letter] is associated with a function of some sort or another, and we now know where they are, what binds to them, what their associations are, and more. [67]

It turns out the parts of our genome that were thought to be “junk DNA” are actually essential for life. This is something that most Darwinists still have not yet come to grips with. Their refusal to accept what the data is plainly showing is not because they have a sound scientific basis to do so. It is because of their unyielding ideological commitment to Darwin. They are well aware that the collapse of the junk DNA story would be a deathblow to Darwinian theory. One ardent evolutionary advocate has gone on record saying,

If the human genome is indeed devoid of junk DNA as implied by the ENCODE project, then a long, undirected evolutionary process cannot explain the human genome… If ENCODE is right, then evolution is wrong [emphasis added]. [68]

That is absolutely true, though he was doing his best to defend the idea of junk DNA when he said this. In order to reject a highly functional genome, the evolutionist must now stand in staunch opposition to the general consensus of the scientific community. Genome scientists have only begun to map the multitude of functions operating throughout the genome, so it is clear that the ENCODE project is just the tip of the iceberg. The more we understand about the various levels of complexity within the cell and the genome, the more functions we are finding and the more impossible random evolution becomes. The rescue mechanisms of junk DNA and neutral evolution are both collapsing simultaneously. This means mankind must be degenerating, and that forward evolution is limited to fine-tuning and minor adaptations, as is consistent with the biblical perspective.

The doctrine of junk DNA was invented out of necessity to save the genome from what leading geneticists, such as Susumu Ohno, referred to as a growing and “unbearably heavy genetic burden.” [69] But now with the collapse of the junk DNA paradigm, the vast numbers of mutations that are always accumulating in what were once assumed to be large “junky” regions of the genome can no longer be considered perfectly neutral. Instead, these very numerous mutations are arising within a largely functional genome. And so while most accumulating mutations were previously assumed to be perfectly neutral, those same mutations must primarily be redefined as “nearly neutral” (or more accurately – very slightly harmful). This must result in continuously increasing genetic entropy – which is genetic degeneration. This also means the evolutionary application of the molecular clock in deep time is indefensible (because most mutations are not perfectly neutral, and will lead to continuous degeneration). It also means that there is much more information in the genome than could ever be explained in terms of natural selection. It means the multiple overlapping codes (not just multiple messages, but multiple languages) in the genome could not possibly arise by mutation/selection. [70] Lastly, the assumption of a common ancestor for man and chimpanzee loses credibility (see below), because much of the supposed evidence for common ancestry was based upon the assumption of pervasive junk DNA. Now that this paradigm is largely falsified, the primary “proofs of ape-to-man evolution” collapse.

Popular “Junk” DNA Claim 1: The shared “mistakes” argument –

The junk DNA argument was really just the genetic application of the outdated “vestigial organs” argument used in the 1800s. Just as all previously claimed “vestigial organs” now have known functions, known functions are being found for all classes of “junk DNA.” For example, humans, chimps, and other apes carry a beta-globulin pseudogene (thought to be a broken version of a once-working gene). Such a “shared mistake” was said to prove that all apes and men have a common ancestor, wherein this “shared mistake” first took place. This sounded like a good argument, until it was recently discovered that the beta-globulin pseudogene is not junk DNA and is not a “shared mistake that proves evolution”, but rather is an essential gene, with its mRNA being essential for healthy blood chemistry and regulating an entire gene family. [71] , [72] , [73] , [74]

A similar story is unfolding regarding “the human vitamin C pseudogene that proves evolution.” Very similar versions of this gene in question are found in both man and ape. It is claimed that this gene has no function – it was broken more than ten million years ago, within the genome of an ancient monkey-like creature. So this gene is “junk DNA,” and its presence in both apes and men is said to prove evolution, because it explains why both apes and men lack the ability to make their own vitamin C (and so must get vitamin C from their diet). It is argued that God would not have made both men and apes with a shared genetic defect.

The logical fallacy is that it is assumed that all animals once had the ability to make vitamin C, and so all those animals that lack this ability must have lost it over deep time due to reductive evolution. This applies to birds, bats, guinea pigs, certain monkeys, apes, humans, etc. This is not a reasonable assumption because all these animals in their natural environment obtain their vitamin C from their diet – they never needed to make it. We suggest that all these animals do not have “broken vitamin C pseudogenes.” Rather we suggest that they have genes that have some similarity to genuine vitamin C genes, and these genes are not broken, they simply have a different function, which for now is still unknown. This view is supported by many other “junk DNA pseudogenes,” which in the end are consistently proving to have important functions. More research needs to be done on this topic before any firm conclusions are made.

Popular “Junk” DNA Claim 2 – The Alleged Chromosome Fusion Event -

For decades evolutionists have claimed that ape-to-man evolution is a proven fact, because our chromosome 2 clearly arose as a fusion of two smaller chimpanzee chromosomes. It has been claimed that the reputed “fusion site” within human chromosome 2 is a vestigial relic (i.e., another type of junk DNA), which records an ancient fusion between two chimp chromosomes to create human chromosome 2. Even if there was evidence that chromosome 2 arose by the fusion of two smaller chromosomes, there is no reason why the two smaller chromosomes could not have been human (from a Biblical perspective such a fusion would have arisen sometime between Adam and Noah). However, there is no need to invoke this explanation because there is now very compelling evidence that shows that the reputed “fusion site” has been falsified. Furthermore there is strong evidence refuting the claim that human chromosome 2 arose by a type of fusion of any kind.

It is true that chimps have a pair of smaller chromosomes, [75] that together are similar (on a gross level) to human chromosome 2. Yet, from a design perspective this is expected. Since the other chromosomes have a general correspondence between the two species, human chr2 would be structurally similar to the two smaller chimp chromosomes if the designer of both genomes chose to use a similar blueprint. Evolutionary geneticists have since acknowledged that such similarities are expected to exist for reasons that have nothing to do with a hypothetical fusion event. As Lopez et al. explain: “…gene order in the genome has been shown to be directly linked to categorical groups of function and transcription in diverse eukaryotes.” [76] Crude similarities in chromosomal architecture are not evidence for fusion events. As the researchers themselves acknowledge about basic chromosome structure, “biochemical function and transcription depend on it.” [77] In other words, different animals share similar chromosome structures simply because they perform similar biochemical functions – not because of chromosome fusions.

By God’s grace, new genetic evidence is showing that the fusion story is not at all credible. The primary evidence for a historical fusion was based upon a very small region of human chromosome 2 that was named “the fusion site.” This very small bit of DNA was heralded for several decades as proof of human evolution. This was because this site contains some traces of what were considered remnants of short telomeric repeat sequences (sequences primarily found at the tips of chromosomes). At that time there were also claims that there were sub-telomeric sequences (repeat elements that appear close to the ends of chromosomes) in the same region (this is now known to be false). There are now many evidences against these long-heralded claims, as summarized in a recent series of scientific papers. [78] , [79] , [80]

Briefly, the evidences against the fusion hypothesis include the following (after Tomkins and Bergman, 2011): [79] , [80]

  1. Chimp chromosomes 2a and 2b are at least 24 million nucleotides longer human chromosome 2. A telomere–to-telomere fusion would not by itself cause any such deletion of sequence.
  2. Although human chromosome 2 has some significant similarities with chimp chromosomes 2a and 2b, this is not true within the general region of the hypothetical fusion site. The entire region (>200 thousand nucleotides long) has no major synteny with any part of chimp 2a or 2b. This is fatal to the fusion hypothesis.
  3. The hypothetical fusion site is within a region that is roughly four thousand nucleotides long, which is unique to man, and has no significant homology to any part of the chimp genome or any part of any sequenced ape genome. This is fatal to the fusion hypothesis.
  4. Contrary to earlier reports, there is no trace in this region of any specific sub-telomeric repeats. In fact, the distinctive sub-telomeric repeats that are unique to chimps and apes are conspicuously absent. This is fatal to the fusion hypothesis.
  5. The hypothetical fusion site itself has very little resemblance to an end-to-end telomeric fusion. Such a fusion would consist of roughly 2,500 copies of the sequence TTAGGG all linked head to toe, followed by about 2,500 copies of the sequence CCCTAA all linked head-to-toe. What is seen is a region that has less than 100 intact copies of TTAGG (not always linked head to toe), followed by less than 100 copies of CCCTAA (not always linked head-to-toe). The fusion site does not really look like an end-to-end fusion site at all. In just 6 million years a sequence such as this could not have undergone such extreme degradation. This is fatal to the fusion hypothesis.
  6. Chromosome fusions do happen, but telomere-to-telomere fusion sites have never been recorded in any living mammal species. This is fatal to the fusion hypothesis.
  7. Telomeric regions generally have very few genes (telomere regions are assumed to be “junky” DNA). But the hypothetical fusion site is surrounded by many genes, none of which are found near the telomeres of chimp chromosomes 2a or 2b. This is fatal to the fusion hypothesis.
  8. The hypothetical fusion site is located internal to a highly expressed and highly regulated human gene. This is fatal to the fusion hypothesis.
  9. The hypothetical fusion site is itself a functional promoter (transcription factor binding site), which appears to have multiple functions in the human genome. There are numerous independent evidences that the hypothetical fusion site is not an evolutionary vestige of an ancient fusion, but is a functional part of the human genome entirely absent in chimpanzee. This is fatal to the fusion hypothesis.
  10. The hypothetical fusion site is a “motif” sequence pattern that includes a short series of telomeric-type repeats. These shorter repeats are not at all unique to telomeres, rather these short motifs are found throughout the human genome. This makes the massively-heralded claims that finding such a sequence is somehow proof of an ancient fusion both unwarranted and reckless.

Like the vestigial organ arguments of old, when we just dig a little deeper, we consistently find that the evolutionary arguments based upon junk DNA assumptions (i.e., shared “mistakes” and a fused chromosome) are not valid. The collapse of the junk DNA paradigm is lethal to evolutionary theory and vindicates the biblical perspective. We only wish that more Christians and theologians knew this!

Junk DNA is a major argument used by advocates of theistic evolution. We cannot answer every one of those arguments here, but will try to do so elsewhere as time permits. The general collapse of the junk DNA paradigm makes all junk DNA arguments tenuous and unpersuasive. We do not claim that all DNA is functional. The genome has been subjected to thousands of years of mutational degeneration. In this light it is expected that our genomes have broken functions, parasitic elements, and lots of genetic debris. But most of the genome must remain functional or we would already be extinct. If most of the genome is functional, then forward evolution becomes impossible for diverse reasons, as numerous Darwinists have acknowledged (see Figure 4).

Figure 4: For over 100 years, Darwinism has ruled the academic world. It was claimed that mutation/selection could explain essentially all biological observations. However, major problems began to emerge in the 1950s when DNA and the genetic code were discovered and mathematical analysis began to reveal evolutionary problems. With the advent of the modern genetic revolution, the explanatory power of Darwinism has plummeted – even as the amount of biological information requiring explanation has exploded. A paradigm shift is inevitable. (Image from ref. [81]).

6. The rise and fall of the ‘near-extinction’ story.

It is now clear that mankind is genetically homogeneous. We have very limited genetic variation compared to other mammals. We are 99.9% identical to each other (with racial distinctions being superficial and recent). Over deep time, any sizeable population will accumulate enormous numbers of mutations, resulting in enormous amounts of genetic diversity. So a very homogeneous human population is a very serious problem for the evolutionary perspective (but is expected from the biblical perspective).

To deal with this serious problem, Darwinists needed a rescue mechanism, and so they invented the concept of a near extinction event for humanity, associated with a severe population bottleneck (with population size declining to the point something like a endangered species - for an extended period of time). This is illustrated in Figures 5 and 6. Any major population bottleneck results in serious genetic damage and species degeneration. For this reason it is very strange to try and explain our limited genetic diversity by invoking a near-extinction event immediately preceding the spectacular emergence of modern man (just before man’s sudden appearance and his rapid conquest of the planet). This hypothetical near-extinction is now thought to have occurred around 70,000 years ago (extremely recently, by evolutionary standards), immediately before the divergence of the different people groups. [82] This would require the global population to decline to much less than 10,000 people for very many generations. Some would argue that humanity shrank down to just 2,000 individuals. [83] The population supposedly stayed at the near-extinction level for a prolonged period of time, resulting in inbreeding and subsequent loss of genetic diversity. This would cause severe inbreeding depression and the fixation of many harmful mutations. In the same general timeframe, this hominin population somehow morphed from apeman (Homo erectus) into modern man (Homo sapiens). Man then rapidly went into unbounded exponential growth, and rapidly spread out onto all the continents while diverging into the various modern people groups. As modern man supposedly was emerging from near-extinction, it is said that he soon mated with the Neanderthals [84] , [85] and the newly-discovered Denisovan [86] , [87] people group, even while man drove Homo erectus to extinction (unless Homo erectus is the same as the Denisovans, which seems likely). This is quite a story and is very problematic. Since it is acknowledged that there were already humans in Africa, Europe, Asia, and Australia, how can anyone claim there was a global bottleneck with inbreeding? If the more modern Africans “came out” into Europe and Asia and then mated with those other people groups, wouldn't that have restored the genetic diversity lost in the reduced African population? The story simply does not hold together. Most importantly, a population bottleneck that amounted to a near-extinction event would have caused permanent and severe genetic damage. How could such a tiny, nearly-extinct, genetically-compromised population suddenly explode into all parts of the planet, seizing dominion over the world? The story is far-fetched and unwarranted. A much better explanation for human homogeneity would be a relatively recent beginning of the human race, with a very small initial population size.

While the hypothetical evolutionary bottleneck might conceivably have reduced overall human diversity, please understand that such a bottleneck is not a natural element of Darwinian theory – it is a rescue mechanism. The bottleneck idea is strictly a post hoc embellishment required to rescue the evolutionary paradigm. It is not even credible. Small, bottlenecked populations have enormous problems. For example, there are approximately 10,000 cheetahs in the world today, and conservationists feel the cheetah is already showing serious signs of inbreeding and genetic decline. There are not enough of them, their genetic diversity has eroded (due to inbreeding), and the species is starting to express many destructive recessive mutations. Cheetah sperm is compromised, and if nothing changes they will quite clearly go extinct. Similarly, the mountain gorilla has experienced a serious population bottleneck, and consequently this species is not just on the verge of extinction, but shows clear evidence of genomic damage, increased genetic load due to the accumulation of deleterious mutations, and severe inbreeding. [88] So is it reasonable to claim that a similar genetic bottleneck in early human history enabled the sudden emergence of modern man with all his unique capabilities?

When the Neanderthal genome was sequenced, the African Bottleneck hypothesis became even more problematic. The evidence is clear: Neanderthal was fully human and inter-mated with Europeans and other people groups. [89] This contradicts the evolutionary near-extinction hypothesis. According to the evolutionary timeline, Neanderthal split away from the main human population about 400,000 years ago, yet was somehow not part of the African near-extinction event. Neanderthal then reunited with the newly emerging human population, which only very recently was coming out of Africa. If Homo sapiens went through a radical genetic reshaping in Africa, how could it remain inter-fertile with Neanderthal? And if Neanderthals, the Denisovans, and Homo erectus (all humans) were outside the genetic bottleneck, then how can it be said that there was ever a real human bottleneck? This scenario clearly fails as a tenable explanation for the observed limited human genetic variability.

The evolutionary bottleneck hypothesis, involving an extended near-extinction event associated with severe inbreeding, is not even remotely feasible. So from the evolutionary perspective human genetic homogeneity remains a very serious theoretical problem. However, from a biblical perspective there is no problem with a relatively homogeneous human population. We start with just two people (constituting an extreme, yet benign “population bottleneck”), and then 10 generations later a second, single-generation bottleneck of just 8 people occurred at the time of Noah. [90] Both bottlenecks were very brief (just one generation) and were followed by explosive growth, and in both cases there would be almost no previously accumulated mutations, hence no harmful inbreeding effects. Very limited human genetic diversity is a huge problem for evolutionary theory and leads to unrestrained storytelling (the evolution story needs to be revised almost annually). Yet limited human genetic diversity is very obviously supportive of the biblical perspective, and does not require any far-fetched mental inventions.

Figure 5: An illustration of a population bottleneck. The colored marbles in the jar on the left represent genetic diversity within a population. If at some time that population is reduced to only a few individuals (the ones poured out into the first cup), when the population begins to rebound (the second cup), it will have lost genetic diversity. Eventually, new mutations will begin to add more genetic diversity (the green marbles in the final bottle), but this takes time. The amount of diversity lost depends on the length of the bottleneck and the size reduction of the bottlenecked population. To explain the general lack of genetic diversity in modern humans, evolutionists have to resort to an extreme, long-duration, extinction-driving bottleneck in the fairly recent past. The biblical model fits the data easily and naturally. (Image courtesy of Creation Ministries International,

Figure 6: “According to the genetic bottleneck theory, between 50,000 and 100,000 years ago, human populations sharply decreased to 3,000–10,000 surviving individuals. It is supported by genetic evidence suggesting that today's humans are descended from a very small population of between 1,000 and 10,000 breeding pairs that existed about 70,000 years ago.” [82] The major genetic problems with this theory are discussed in the text.

7. The rise and fall of the Double ‘Out of Africa’ Paradigm

Most people do not realize that the most common version of the evolutionary story of man involves not one, but two, Out-of-Africa events. There are various versions of this story, which can become very confusing. Ancient humans (Homo erectus) supposedly arose from apes in Africa, then spread out to also colonize Eurasia and Australia. Homo erectus in Europe evolved into Neanderthal people. In Eurasia Homo erectus supposedly evolved into the enigmatic Denisovan people. Sometime after that, anatomically modern humans supposedly evolved from Homo erectus in Africa just before these new Africans (Homo sapiens) experienced a hypothetical near-extinction bottleneck. So Homo erectus is said to have evolved independently into Homo sapiens, Neanderthal, and the Denisovans. Does it seem credible that the modern human brain and modern mental capabilities evolved independently three times? After a severe genetic bottleneck, the African derivative of Homo erectus (Homo sapiens) is said to have experienced a population explosion in northeastern Africa – spilling out into Eurasia – constituting a second emergence out of Africa. Along the way, these modern humans hybridized with both the Neanderthals and Denisovans while simultaneously replacing Homo erectus. Then Homo sapiens rapidly diverged into the modern people groups (see Figure 7). The first part of this scenario seems contrived and convoluted storytelling. That part of the story has continuously undergone reconstruction ever since the time of Darwin. However, the later part of the story actually closely matches the biblical accounts of early man (with a diaspora of modern man suddenly coming out of the Middle East/NE Africa followed by rapid divergence of the people groups) (see Figure 7).

The alternative point of view, the biblical perspective, is not based upon inference or speculation, but is primarily based upon ancient historical records. Those ancient records indicate that man came out of the Middle East (Babylon) in the recent past (note: on a global scale, Babylon and northeastern Africa are essentially the same geographic region). The observed genetic differences between today’s people groups would very logically be the result from the diaspora out of Babylon – due to the fragmentation of the human population according to patriarchal clan, as well as being due to genetic founder effects and assortative (preferential) mating. Given the higher level of genetic diversity in Africa, the biblical model would require that: a) after the Tower of Babel event, more clans moved into Africa than into Europe or Asia or b) that the African tribes remained smaller in size and were more isolated from each other for a longer period of time [91] or c) some combination of these factors. This scenario is faithful to both genetic reality and the biblical parameters.

We presume Neanderthal and other mutant forms of the modern human family (Denisovans?), either split away from the Tower of Babel community early (before the Babel dispersion), or were simply the first tribes to arrive in Eurasia after the Babel event. The extreme genetic uniformity of the Neanderthal [92] is contrary to the notion that Neanderthal was an extremely ancient and widely distributed people group. Such genetic uniformity is most consistent with Neanderthals being the result of an extreme founder event, with a tiny inbred group of genetically deviant people splitting away from the rest of humanity some time before the main diaspora out of the Middle East. This group could have initially been as small as an outcast brother and sister, who were forced into hunting and gathering, with their offspring scattering and colonizing Eurasia before the main Babel dispersion.

Overall, the biblical perspective seems to fit the observed worldwide genetic pattern best, while the evolutionary perspective is more convoluted and far-fetched. Darwin thought the human “races” were profoundly different (sub-species) and must have diverged over millions of years. Modern genetics is now revealing that “race” is really a superficial classification based primarily on skin color. There is very little genetic basis for justifying the term “race” instead it seems more accurate to say that the original human population separated into tribes – which became people groups and nations. Modern genetics is also revealing that the people groups clearly diverged very recently and very rapidly. [93] , [94] While the evolutionists assume that racial divergence arose through a gradual process of mutation accumulation, the genetic differences between people groups require neither new mutations nor extended time. All that is required is population fragmentation and rapid dispersal. This results in nearly instantaneous “founder effects” for each tribe (i.e., differential sampling from the original gene pool). After that, assortative mating and continued inbreeding within each group would accentuate those traits characteristic of each tribe and people group. [95] Some limited amount of selection would also be occurring. The genetic evidence is best understood in terms of the Babylonian dispersal, with the people groups diverging very rapidly in the very recent past.

Figure 7: The evolutionary out-of-Africa Model compared to the biblical Adam/Flood/Babel model. The y-axis shows population size (on an arbitrary scale). The x-axis shows time (also on an arbitrary scale). In the Out of Africa scenario (red line), humans lived as Homo erectus in Africa for perhaps a million years with a population size of maybe a million individuals (flat red line). Only a few tens of thousands of years ago, that population went through a prolonged and degenerative bottleneck (the sharp dip downward), during (or just prior to) the evolution of Homo sapiens. Then Homo sapiens had an explosive recovery, filling the world and producing the diverse people groups. The biblical view (black line) is very similar, but minus the long flat line when apes were evolving into modern man.

From a biblical perspective there has been a spiritual battle raging ever since the Fall took place in the Garden of Eden. In the words of Henry Morris Jr., this has manifested itself as The Long War Against God. [96] Those who are at war against God have systematically attacked His Character, His Plan, His Word, and His People. The hostility toward God’s Word is widespread and increasing. Remarkably, this is true even within the Church, where many leaders consider themselves to be part of the intellectual elite, and as such consider themselves too enlightened to submit to God and His Word - as understood in His Church from the beginning. This hostility toward God’s Word reaches a crescendo when certain foundational elements of Catholic doctrine are addressed. These crucial issues include: a) a miraculous and perfect creation b) a literal Adam and Eve c) the reality of Satan and a literal Fall and d) the historical emergence of modern people groups out of Babylon. Isn’t it interesting that each of these fundamental doctrines has a distinct genetic component, as we have outlined in this paper?

If there really is a spiritual war raging, then it should hardly be surprising that these essential Christian doctrines would be attacked. But by God’s grace and thanks to modern genetics we now have powerful arguments to defend these foundational doctrines and to defend the biblical perspective of family. Similarly, by God’s grace we now have many genetic evidences that strongly refute the powerful deception that man evolved from chimpanzee, and that human family unit evolved from the Chimp family unit.

During this “the long war against God,” some Christians have faithfully stood their ground on these essential Christian doctrines. At times, for lack of correct information, they have retreated to a position of simple faith when confronted with evolutionary claims that appeared to be unassailable scientific facts. When it seemed as if they must choose between faith in God versus faith in scientists, they chose faith in God. At the same time, other Christians chose faith in scientists, thereby purchasing for themselves academic respectability at the price of spiritual retreat and abandonment of essential Christian doctrines. Now, by God’s grace, Christians do not have to choose between biblical faith versus current scientific evidence. There is now very good scientific evidence that strongly supports Scripture and refutes evolution. Will Church leaders eagerly explore and embrace these evidences that God is mercifully providing? Will they encourage faithful Christians to consistently trust God more, and trust human authority less? As we stand at this crossroads, our Church leadership seems to hold the future of the Christian family in their hands.

Acknowledgment: We thank Chris Rupe for his assistance in pulling together this paper and significantly enhancing its quality.

[2] R. W. Carter, Mitochondrial diversity within modern human populations, Nucleic Acids Research 35(9):3039- 3045, 2007, accessed 9/8/2015.

[3] L. Madrigal et al., High Mitochondrial Mutation Rates Estimated From deep-rooting Costa Rican pedigrees, American Journal of Physical Anthropology 148:327-333, 2012.

[4] O. Venn et al. Strong male bias drives germline mutation in chimpanzees, Science 344:1272-1275, 2014.

[5] J. F. Hughes et al., Chimpanzee and Human Y Chromosomes are Remarkably Divergent in Structure and Gene Content, Nature 463:536-539, 2010.

[8] J. C. Sanford and R. W. Carter, In Light of Genetics. Adam, Eve, and the Creation/Fall. Originally published in Christian Apologetics Journal, Vol. 12, No. 2, Fall 2014 by Southern Evangelical Seminary.

[10] G. D. Poznik et al., Sequencing Y Chromosomes Resolves Discrepancy in Time to Common Ancestor of Males Versus Females, Science 341:562-565, 2013.

[11] Francis Collins, Noted scientist tackles question of religious faith, 2011 accessed: 08/08/15

[13] K. A. Frazer et al., International HapMap Consortium, A second generation human haplotype map of over 3.1 million SNPs, Nature 449:851-862, 2007.

[14] R. W. Carter, The Non-Mythical Adam and Eve! Refuting errors by Francis Collins and BioLogos, 2011 accessed: 11/25/14

[15] J. A. Tennessen et al., Evolution and Functional Impact of Rare Coding Variation from Deep Sequencing of Human Exomes, Science 337(6090):64-69, 2012.

[16] Human Y-chromosome “family tree” modified from P. Hallast et al., The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades. Mol Biol Evol 32(3):661-673, 2015.

[17] J. C. Sanford, J. Pamplin, and C. Rupe, The most famous evolution experiment of all time shows that evolution goes the wrong way!lenski/c23yt, 2015, accessed 9/8/2015.

[18] C. Hardy and R. W. Carter, The biblical minimum and maximum age of the earth, Journal of Creation 28(2) 2014, accessed 9/8/2015.

[19] J. F. Crow, The high spontaneous mutation rate: Is it a health risk? Proceedings of the National Academy of Sciences (USA) 94(16):8380–8386, 1997.

[20] M. Lynch, Rate, molecular spectrum, and consequences of human mutation, Proceedings of the National Academy of Sciences (USA) 107(3):961–968, 2010.

[21] J. C. Sanford et al., Mendel’s Accountant: a biologically realistic forward-time population genetics program. Scalable Computing: Practice and Experience 8(2):147–165, 2007, accessed 9/8/2015.

[22] J. C. Sanford et al., Using computer simulation to understand mutation accumulation dynamics and genetic load. ICCS 2007, Part II, LNCS (Y. Shi et al., eds.), 4488:386–392, 2007, accessed 9/8/2015.

[23] J. Baumgardner et al., 2008. Mendel’s Accountant: A New Population Genetics Simulation Tool for Studying Mutation and Natural Selection, accessed 9/8/2015.

[24] J. C. Sanford et al. 2008. Using Numerical Simulation to Test the Validity of Neo-Darwinian Theory. In A. A. Snelling (Ed.) (2008). Proceedings of the Sixth International Conference on Creationism (pp. 165–175). Pittsburgh, PA: Creation Science Fellowship and Dallas, TX: Institute for Creation Research. Simulation-to-Test-the-Validity-of-Neo-Darwinian-Theory.pdf, accessed 9/8/2015.

[25] J. C. Sanford and N. Nelson, The Next Step in Understanding Population Dynamics: Comprehensive Numerical Simulation, Studies in Population Genetics (M. Carmen Fusté, ed.), InTech, Rijeka, Croatia, 2012, accessed 9/8/2015.

[26] J. C. Sanford et al., Selection threshold severely constrains capture of beneficial mutations, Biological Information: New Perspectives (R. J. Marks III et al. eds.), 264-297, 2013, accessed 9/8/2015.

[27] P. Gibson et al. Can purifying natural selection preserve biological information? Biological Information: New Perspectives (R. J. Marks III et al., eds.), 232-263, 2013, accessed 9/8/2015.

[28] W. Brewer et al., Using numerical simulation to test the “mutation-count” hypothesis, Biological Information: New Perspectives (R. J. Marks III et al., eds.), 298-311, 2013, accessed 9/8/2015.

[29] J. Baumgardner et al., Can synergistic epistasis halt mutation accumulation? Results from numerical simulation, Biological Information: New Perspectives (R. J. Marks III et al., eds.), 312-337, 2013, accessed 9/8/2015.

[31] P.M. Holladay and J.M. Watt, De-generation: an exponential decay curve in old testament genealogies. Evangelical Theological Society Papers. 52 nd Natl. Conf., Nashville, TN Nov. 15-17, 2000.

[32] J. C. Sanford, J. Pamplin and C. Rupe, Genetic Entropy Recorded in the Bible?!genetic-entropy/chft, 2014, accessed 9/8/2015.

[33] Carl Sagan, Cosmos, 1980, p. 3.

[34] J.L. Arsuaga, The Neanderthal’s Necklace (Four Walls Eight Windows, NY), p.3, 2002.

[35] J. Bronowski, “The Ascent of Man,” a television series produced by the BBC and Time-Life Films, 1973.

[36] R.J. Britten, Divergence between samples of chimpanzee and human DNA sequences is 5%, counting indels, Proceedings of the National Academy of Sciences 99(21):13633-13636, 2002.

[37] T.J. Preuss, Human brain evolution: From gene discovery to phenotype discovery, Proceedings of the National Academy of Sciences 109(suppl. 1):10709-10716, 2012.

[38] J.F. Hughes et al., Chimpanzee and Human Y Chromosomes are Remarkably Divergent in Structure and Gene Content, Nature 463:536-539, 2010.

[39] J. Tomkins and J. Bergman, Genomic monkey business—estimates of nearly identical human–chimp DNA similarity re-evaluated using omitted data, Journal of Creation 26(1)=:94-100, 2012, accessed 9/8/2015.

[40] J. Tomkins and J. Bergman, Is the human genome nearly identical to chimpanzee?—a reassessment of the literature, Journal of Creation 26(1):54-60, 2012, accessed 9/8/2015.

[41] J. Cohen, Relative Differences: The Myth of 1%, Science 316:1836, 2007.

[42] J. Sanford, W. Brewer, F. Smith, J. Baumgardner, The Waiting Time Problem in a Model Hominin Population. Theoretical Biology and Medical Modeling, 12:18 (2015) accessed 9-17-15

[43] R. Durrett and D. Schmidt, Waiting for regulatory sequences to appear. The Annals of Applied Probability 17(1):1-32, 2007.

[45] J.C. Sanford et al., Mendel’s Accountant: a biologically realistic forward-time population genetics program. Scalable Computing: Practice and Experience 8(2):147–165, 2007.

[46] J.C. Sanford et al., Selection threshold severely constrains capture of beneficial mutations, in Biological Information: New Perspectives, (R.J. Marks III et al., eds.), , 264-297, 2013.

[47] C.W. Nelson and J.C. Sanford, Computational evolution experiments reveal a net loss of genetic information despite selection, in Biological Information: New Perspectives, (R. J. Marks III et al., eds.), 338-368, 2013.

[48] J.F. Crow, The high spontaneous mutation rate: is it a health risk? Proceedings of the National Academy of Sciences 94:8380-8386, 1997.

[49] A.S. Kondrashov, Contamination of the genome by very slightly deleterious mutations: why have we not died 100 times over? Journal of Theoretical Biology 175:583-594, 1995.

[50] M. Lynch, Rate, molecular spectrum, and consequences of human mutation. Proceedings of the National Academy of Sciences 107(3):961-968, 2010.

[51] J.C. Sanford, Genetic Entropy, FMS Publications, 2014.

[52] J.C. Sanford et al., Mendel’s Accountant: a biologically realistic forward-time population genetics program. Scalable Computing: Practice and Experience 8(2):147–165, 2007, accessed 9/8/2015.

[53] J.C. Sanford et al., Using computer simulation to understand mutation accumulation dynamics and genetic load. ICCS 2007, Part II, LNCS (Y. Shi et al., eds.), 4488:386–392, 2007, accessed 9/8/2015.

[54] J.C. Sanford and C. Nelson, The Next Step in Understanding Population Dynamics: Comprehensive Numerical Simulation, Studies in Population Genetics (M. Carmen Fusté, ed.), InTech, Rijeka, Croatia, 2012, accessed 9/8/2015.

[55] W. Brewer et al., Using numerical simulation to test the “mutation-count” hypothesis, in Biological Information: New Perspectives (R.J. Marks III et al., eds.), 298-311, 2013, accessed 9/8/2015.

[56] J. Baumgardner et al., Can synergistic epistasis halt mutation accumulation? Results from numerical simulation, in Biological Information: New Perspectives (R.J. Marks III et al., eds.), 312-337, 2013, accessed 9/8/2015.

[57] P. Gibson et al. Can purifying natural selection preserve biological information? in Biological Information: New Perspectives (R.J. Marks III et al., eds.), 232-263, 2013, accessed 9/8/2015.

[58] J.C. Sanford et al., Selection threshold severely constrains capture of beneficial mutations, in Biological Information: New Perspectives (R.J. Marks III et al., eds.), 264-297, 2013 [URL missing!]

[59] R.W. Carter and J.C. Sanford, A new look at an old virus: mutation accumulation in the human H1N1 influenza virus since 1918, Theoretical Biology and Medical Modeling 9:42, 2012, accessed 9/8/2015.

[60] R.W. Carter, Mitochondrial diversity within modern human populations, Nucleic Acids Research 35(9):3039- 3045, 2007, accessed 9/8/2015.

[61] C. Rupe and J. Sanford, The most famous evolution experiment of all time shows that evolution goes the wrong way!lenski/c23yt, 2015, accessed 9/8/2015.

[62] S. Ohno, So Much ‘Junk’ DNA in Our Genome, Brookhaven Symp Biol 23:366-70, 1972.

[63] M. Kimura, Evolutionary rate at the molecular level, Nature 217:624-626, 1968.

[64] The ENCODE Project Consortium, An integrated encyclopedia of DNA elements in the human genome. Nature 489:57-74, 2012.

[65] R. W. Carter, “Splicing and dicing the human genome: scientists begin to unravel the splicing code,” Creation Ministries International (July 1, 2010), accessed 08/08/15

[66] E. Pennisi, Encode Project Writes Eulogy for Junk DNA, Science 337:1159-1161, 2012.

[67] E. Yong, ENCODE: the rough guide to the human genome, Discover Magazine, Sep 5, 2012.

[69] S. Ohno, So Much ‘Junk’ DNA in Our Genome, Brookhaven Symp Biol 23:366-70, 1972.

[70] G. Montañez, R. Marks, J. Fernandez, and J. Sanford, Multiple overlapping genetic codes profoundly reduce the probability of beneficial mutation, in Biological Information – New Perspectives (R.J. Marks III et al., eds.), 139-167, 2013 pdf/10.1142/9789814508728_0006, accessed 9/8/2015.

[71] J.P. Tomkins, The human Beta­globin pseudogene is non­variable and functional, Answers Research Journal 6:293-301, 2013, accessed 9/8/2015.

[72] M. Nuinoon et al., A genome-wide association identified the common genetic variants influence disease severity in beta0-thalassemia/hemoglobin E. Human Genetics 2010,127(3): 303–314.

[73] P. Roy et al., Influence of BCL11A, HBS1L-MYB, HBBP1 single nucleotide polymorphisms and the HBG2 XmnI polymorphism on Hb F levels. Hemoglobin 36(6) 592–599, 2012.

[74] E. Giannopoulou et al., A single nucleotide polymorphism in the HBBP1 gene in the human B-globin locus is associated with a mild B-thalassemia disease phenotype. Hemoglobin 36(5):433-445, 2012.

[75] They were previously numbered chromosome 12 and 13, but because the assumption of human evolution required that these chromosomes must have once fused to yield human chromosome 2, they were renamed “2a” and “2b”. This is the only example in the entire field of genetics where the chromosomes of a species are not numbered in size order.

[76] M.D. Lopez, J.J.M. Guerra, and T. Samuelsson, Analysis of gene order conservation in eukaryotes identifies transcriptionally and functionally linked genes, PloS ONE 5(5), 2010.

[78] J. Tomkins, Alleged human chromosome 2 ‘fusion site’ encodes an active DNA binding domain inside a complex and highly expressed gene—negating fusion, Answers Research Journal 6:367-375, 2013, accessed 9/8/2015.

[79] J. Tomkins and J. Bergman, The chromosome 2 fusion model of human evolution—part 1: re-evaluating the evidence, Journal of Creation 25(2):106-110,2011, accessed 9/8/2015.

[80] J. Tomkins and J. Bergman, The chromosome 2 fusion model of human evolution—part 2: re-analysis of the genomic data, Journal of Creation 25(2):111-117, 2011, accessed 9/8/2015.

[81] J. Sanford, Biological Information and Genetic Theory: Introductory Comments, Biological Information – New Perspectives (R.J. Marks et al., eds.), World Scientific, 2013.

[82] There are many variations on this basic story. See, for example,, accessed 9/8/2015.

[83] M.C. Campbell and S.A. Tishkoff, The Evolution of Human Genetic and Phenotypic Variation in Africa, Current Biology 20(4) pR166-R173, 2010.

[84] R.E. Green et al., A draft sequence of the Neandertal genome, Science, 328(5979):710–722, 2010.

[85] R.W. Carter, Neandertal genome like ours (There may be Neandertals at your next family reunion!)” Creation Ministries (June 1, 2010), accessed 08/08/15,

[86] D. Reich et al., Genetic history of an archaic hominin group from Denisova Cave in Siberia, Nature, 468:1053-1060, 2010.

[87] A.J. Jeffreys and C. A. May, Intense and highly localized gene conversion activity in human meiotic crossover hot spots, Nature Genetics, 36:151-156, 2004.

[88] Y. Xue et al., Mountain gorilla genomes reveal the impact of long-term population decline and inbreeding, Science, 348:242-245, 2015.

[89] Q. Fu et al., Genome sequence of a 45,000-year-old modern human from western Siberia, Nature, 514: 445-450, 2014.

[90] R. W. Carter, “Adam, Eve and Noah vs Modern Genetics,” Creation Ministries (May 11, 2010), accessed 08/11/

[91] D.M. Behar et al., The Dawn of Human Matrilineal Diversity, American Journal of Human Genetics 82:1130-1140, 2008.

[92] D. Reich et al., Genetic history of an archaic hominin group from Denisova Cave in Siberia, Nature, 468(7327):1053-1060, 2010.

[93] A. Keinan and A.G. Clark, Recent Explosive Human Population Growth Has Resulted in an Excess of Rare Genetic Variants, Science, 336(6082):740–743, 2012.

[94] M. Nelson, An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People, Science, 337(6090):100-104, 2012.

Mendel and Genetics Experiments with Peas: 1856 to 1863

During his time in Olomouc, Mendel had made friends with two university professors: Friedrich Franz, a physicist, and Johann Karl Nestler, an agricultural biologist, who was interested in heredity.

Nestler passed his interest in heredity to Mendel, who was intrigued by the subject.

Mendel’s monastery had a 5 acre (2 hectare) garden, and his two former professors encouraged Mendel to pursue his interest in heredity by using the garden for experiments.

Abbot Franz Cyril Napp and Professor Franz Diebl also encouraged him to follow this path.

Mendel was unhappy with how inheritance of traits was being explained

People had known for millennia about selective breeding. They knew that by breeding from those individuals that showed the most desirable traits, future generations were more likely to show these desirable traits.

  • Guard dogs might be bred from parents that were loyal and friendly to their owners, but were suspicious or even aggressive with strangers.
  • Cattle might be bred from cows that yielded most milk and bulls that yielded most meat.
  • Wheat might be kept and sown the following year from those plants which had produced the most abundant crop.

The main theory of heredity in Mendel’s time was that offspring were a smooth blend of their two parents’ traits.

Mendel set himself the very ambitious task of discovering the laws of heredity.

To achieve this, he embarked on a mammoth sized, highly systematic, eight year study of edible peas, individually and carefully recording the traits shown by every plant in successive generations.

His work involved growing and recording the traits in about 30,000 plants.

One of the keys to his success was that he bred from closely related pea varieties that would differ in only a small number of traits.

The seven traits of pea plants that Mendel chose to study: seed wrinkles seed color seed-coat color, which leads to flower color pod shape pod color flower location and plant height. Image by Mariana Ruiz.

Mendel’s Results for Flower Color

Mendel found the same results for all traits, but we’ll look at flower color as an example.

When Mendel bred purple-flowered peas (BB) with white-flowered peas (bb), every plant in the next generation had only purple flowers (Bb).

When these purple-flowered plants (Bb) were bred with one-another to create a second-generation of plants, some white flowered plants appeared again (bb).

Mendel realized that his purple-flowered plants still held instructions for making white flowers somewhere inside them.

He also found that the number of purple to white was predictable.

75 percent of the second-generation of plants had purple flowers, while 25 percent had white flowers. He called the purple trait dominant and the white trait recessive.

A Punnett Square. Both of the starting plants have purple flowers but they contain the genes for purple (B) and white (b). The pollen from the male plant fertilizes the egg in the female flower. In this variety of plant, purple flowers are caused by a dominant gene (B). Dominance is indicated by a capital letter. White flowers are caused by recessive genes, indicated by the small letter (b). Both the male and female parent plants in the diagram above carry the dominant gene B for purple and the recessive gene b for white flowers. The ratio of purple flowers to white flowers in their offspring will be 3:1 as shown in this diagram. For a white flower to appear, the offspring must inherit the recessive gene from both parents. Purple appears with any other combination of genes inherited from the parent plants. Image by Madeleine Price Ball

Mendel’s Conclusions

Mendel’s most important conclusions were:

  • The inheritance of each trait is determined by something (which we now call genes) passed from parent to offspring unchanged. In other words, genes from parents do not ‘blend’ in the offspring.
  • For each trait, an organism inherits one gene from each parent.
  • Although a trait may not appear in an individual, the gene that can cause the trait is still there, so the trait can appear again in a future generation.

Scientists who did research later found that Mendel’s results do not only apply to pea plants. Trait inheritance in most plants and animals, including humans, follows the patterns Mendel recorded.

In Mendel’s honor, these very common patterns of heredity are now called Mendelian Inheritance.

Fast Forward to 1900: The Sleeping Giant Awakes

In 1900, three scientists independently carrying out heredity research got exciting results.

However, when they searched the literature, they realized their results were not really new. Their results actually verified the forgotten results Mendel had published 34 years earlier.

Mendel’s results gave the scientists of 1900 greater confidence in their own results and the new science of genetics was truly born.

The scientists were Carl Correns, Hugo de Vries, and Erich von Tschermak.

“I thought that I had found something new. But then I convinced myself that the Abbot Gregor Mendel in Brünn, had, during the sixties, not only obtained the same result through extensive experiments with peas, which lasted for many years, as did de Vries and I, but had also given exactly the same explanation, as far as that was possible in 1866.”

Mendel’s Results Were “Too Good”

Mendel’s published work was rather vague about experimental procedures, including dates.

Enter Ronald Fisher, a very eminent geneticist and statistician. It was Fisher who first used the term ‘null hypothesis’ in statistical testing.

In 1936, Fisher tried to reconstruct on paper the way Mendel carried out his experiments.

He also wanted to discover why Mendel’s work had been overlooked for so long until it was rediscovered in 1900.

He found that, although some people in a position to see the importance of Mendel’s work had actually read it, they did not realize its importance. Their minds were unreceptive to Mendel’s words and ideas. They may have believed he was repeating plant hybridization work others had already carried out.

Controversially, Fisher said that his statistical analysis of Mendel’s results showed too few random errors to have come from real experiments.

“Although no explanation can be expected to be satisfactory, it remains a possibility among others that Mendel was deceived by some assistant who knew too well what was expected. This possibility is supported by independent evidence that the data of most, if not all, of the experiments have been falsified so as to agree closely with Mendel’s expectations.”

Fisher’s analysis said there was only a 1 in 2000 chance that Mendel’s results were the fully reported results of real experiments.

The controversy started by Fisher continues to this day, with a steady stream of publications seeking to give reasons for Mendel’s results. One possibility is that results from ‘bad’ experiments were discarded to leave only the results of ‘good’ experiments. Another is that the results arose from an unconscious bias on the part of the experimenters.

The End

Gregor Mendel was unaware of the new science of genetics he founded and unaware of any future controversies. He died, aged 61, of kidney disease on January 6, 1884.

Author of this page: The Doc
Images of scientists digitally enhanced and colorized by this website.
© All rights reserved.

Mendel's Crosses

Mendel tracked heritable characters for three generations. In the first generation, the P generation (parental generation), Mendel crossed two "true-breeding" parents with differing traits for one or more characters. "True-breeding" means that all of the offspring of that individual have the same trait as the parent when the offspring are produced by self-pollination. In this figure, the individual with white flowers was true-breeding because all of the offspring produced from a self-pollination had white flowers. Similarly, the individual with purple flowers only produced offspring with purple flowers when self-pollinated.

The crossing of two true-breeding parents produced an F1 generation of hybrid individuals that exhibited only the trait found in one of the two parents. The trait that was expressed in the F1 generation was termed a dominant trait. The F1 generation hybrids were then each self-pollinated, producing an F2 generation. Although not present in the F1 generation, the trait exhibited by the one parent reappeared in this generation, invariably at approximately a 3:1 ratio of one parental trait to the other. The trait that reappeared in the F2 generation was termed a recessive trait because it receded in the previous generation. Mendel counted large numbers (hundreds to thousands) of offspring in the F2 generation, allowing him to analyze his results mathematically from which he determined the mode and manner of inheritance in this species.

Figure. Mendel tracked heritable characters for three generations. (Click image to enlarge)

University General Education Requirements

All undergraduate students at the University of Wisconsin–Madison are required to fulfill a minimum set of common university general education requirements to ensure that every graduate acquires the essential core of an undergraduate education. This core establishes a foundation for living a productive life, being a citizen of the world, appreciating aesthetic values, and engaging in lifelong learning in a continually changing world. Various schools and colleges will have requirements in addition to the requirements listed below. Consult your advisor for assistance, as needed. For additional information, see the university Undergraduate General Education Requirements section of the Guide.

  • Breadth—Humanities/Literature/Arts: 6 credits
  • Breadth—Natural Science: 4 to 6 credits, consisting of one 4- or 5-credit course with a laboratory component or two courses providing a total of 6 credits
  • Breadth—Social Studies: 3 credits
  • Communication Part A & Part B *
  • Ethnic Studies *
  • Quantitative Reasoning Part A & Part B *

14.15: Introduction to the Father of Genetics - Biology


Hail to the "Father of Genetics" !

My name is ma-ma-ma-ma-ma-Mendel. There are a few important vocabulary terms we should iron-out before diving into Mendel's Laws .

    Now, turns out there are three possible GENOTYPES - two big letters (like "TT"), one of each ("Tt"), or two lowercase letters ("tt"). Since WE LOVE VOCABULARY, each possible combo has a term for it.

    When we have two capital or two lowercase letters in the GENOTYPE (ex: TT or tt ) it's called HOMOZYGOUS ("homo" means "the same"). Sometimes the term " PURE " is used instead of homozygous.

    When the GENOTYPE is made up of one capital letter & one lowercase letter (ex: Tt ) it's called HETEROZYGOUS ("hetero" means "other"). Just to confuse you, a heterozygous genotype can also be referred to as HYBRID . OK?

    Let's Summarize:

    Genotype = genes present in an organism (usually abbreviated as two letters)
    TT = homozygous = pureTt = heterozygous = hybridtt = homozygous = pure
    For example, there is a gene for hair texture (whether hair is curly or straight). One form of the hair texture gene codes for curly hair. A different code for of the same gene makes hair straight. So the gene for hair texture exists as two alleles --- one curly code, and one straight code.

    Let's try & illustrate with a diagram.
    In this picture the two "hot dog" shapes represent a pair of homologous chromosomes. Homologous chromosomes are the same size & have the same genetic info (genes). Each letter in the diagram stands for an allele (form of a gene). What's important to notice is that the letters can be in different forms (capital or lowercase) --- that is what we mean by allele --- and that the letters are lined-up in the same order along each hot dog --- I mean homologous chromosome. The "a-forms" are in corresponding positions, so are the "B-forms", the "c" alleles, the "d" alleles, etc. etc. OK?
    Reread that "allele" definition again & study the picture.

    Getting back to our abbreviations, we could use a "C" for the curly allele, and a "c" for the straight allele. A person's genotype with respect to hair texture has three possiblilties: CC, Cc, or cc. So to review some vocab, homozygous means having two of the same allele in the genotype (2 big or 2 little letters --- CC or cc). Heterozygous means one of each allele in the genotype (ex: Cc).

    Now I could tell you which genotypes create curls & which do not, but then I'd be stealing some of Mr. Mendel's thunder. More on that in a minute .

Vocabulary Review Questions

1. Which of the following is a possible abbreviation for a genotype?

Ma-Ma-Ma-Ma-Mendel's First Law

The Law of Dominance
Stated "simply" it goes like so:
In a cross of parents that are pure for contrasting traits, only one form of the trait will appear in the next generation. Offspring that are hybrid for a trait will have only the dominant trait in the phenotype.

While Mendel was crossing (reproducing) his pea plants (over & over & over again), he noticed something interesting. When he crossed pure tall plants with pure short plants, all the new pea plants (referred to as the F1 generation) were tall. Similarly, crossing pure yellow seeded pea plants and pure green seeded pea plants produced an F1 generation of all yellow seeded pea plants. The same was true for other pea traits:

Parent Pea Plants F1 Pea Plants
tall stem x short stem all tall stems
yellow seeds x green seeds all yellow seeds
green pea pods x yellow pea pods all green pea pods
round seeds x wrinkled seeds all round seeds
axial flowers x terminal flowers all axial flowers

So, what he noticed was that when the parent plants had contrasting forms of a trait (tall vs short, green vs yellow, etc.) the phenotypes of the offspring resembled only one of the parent plants with respect to that trait. So, he said to himself, "Greg, there is a factor that makes pea plants tall, and another factor that makes pea plants short. Furthermore Greg ol' boy, when the factors are mixed, the tall factor seems to DOMINATE the short factor".

Let's revisit the three possible genotypes for pea plant height & add some MORE VOCABULARY.

Genotype Symbol Genotype Vocab Phenotype
TT homozygous DOMINANT
pure tall
Tt heterozygous
tt homozygous RECESSIVE
pure short

Note: the only way the recessive trait shows-up in the phenotype is if the geneotype has 2 lowercase letters (i.e. is homozygous recessive).
Also note: hybrids always show the dominant trait in their phenotype (that, by the way, is Mendel's Law of Dominance in a nutshell).

The PUNNETT SQUARE (P-Square for short)

OK, now is as good of time as any to introduce you to a new friend, the Punnett Square. This little thing helps us illustrate the crosses Mendel did, and will assist you in figuring out a multitude of genetics problems.

We will start by using a P-Square to illustrate Mendels Law of Dominance. Recall that he "discovered" this law by crossing a pure tall pea plant & a pure short pea plant. In symbols, that cross looks like this:

where T = the dominant allele for tall stems
& t = recessive allele for short stems

The P-Square for such a cross looks like this:
Inside the 4 boxes are the possible genotypes (with respect to plant height) of the offspring from these parent pea plants. In this case, the only possible genotype is Tt (heterozygous). In hybrids, the dominant trait (whatever the capital letter stands for) is the one that appears in the phenotype, so all the offspring from this cross will have tall stems.

To "fill in the boxes" of the Punnett Square, say to yourself "letter from the left & letter from the top". The "t" from the left is partnered with the "T" from the top to complete each of the four squares.

A summary of this cross would be:

Parent Pea Plants
(P Generation)
(F1 Generation)
TT x tt
tall x short
100% Tt
100% tall

Now, a helpful thing to recognize is this:


Does setting up & using the Punnett Square confuse you? Would you like to see a step-by-step "how to" about the good ol' p-square?
If you said "yes", then check this out: "The Punnet Square (in baby steps)".

For some practice Punnett Square problems visit my very own: "P-Square Practice Page".

Don't forget to come back & learn more about Mendel!

Ma-Ma-Ma-Ma-Mendel's Second Law

The Law of Segregation
Goes like so: During the formation of gametes (eggs or sperm), the two alleles responsible for a trait separate from each other. Alleles for a trait are then "recombined" at fertilization, producing the genotype for the traits of the offspring.

The way I figure it, Mendel probably got really bored crossing pure dominant trait pea plants with pure recessive trait pea plants (over & over & over again) & getting nothing but pea plants with the dominant trait as a result. Except for gaining more & more evidence for his Law of Dominance, this probably grew tiresome. So, at one point he takes the offspring of a previous cross & crosses them. Ooooooooh .

Recall that his original cross for the tall & short pea plants was:

Parents F1 Offspring
Genotype(s) TT x tt 100% Tt
Phenotype(s) tall x short 100% tall

So, he takes two of the "F1" generation (which are tall) & crosses them. I would think that he is figuring that he's gonna get all tall again (since tall is dominant). But no! Low & behold he gets some short plants from this cross! His new batch of pea plants (the "F2" generation) is about 3/4 tall & 1/4 short. So he says to himself, "Greg ol' boy, the parent plants for this cross each have one tall factor that dominates the short factor & causes them to grow tall. To get short plants from these parents, the tall & short factors must separate, otherwise a plant with just short factors couldn't be produced. The factors must SEGREGATE themselves somewhere between the production of sex cells & fertilization."

I think it's easier to picture this law by using a p-square. Our cross is two hybrid parents, Tt x Tt.
The punnet square would look like this:
Now, when completing a Punnet Square, we model this "Law of Segregation" every time. When you "split" the genotype letters & put one above each column & one in front of each row, you have SEGREGATED the alleles for a specific trait. In real life this happens during a process of cell division called " MEIOSIS ". Meiosis leads to the production of gametes (sex cells), which are either eggs or sperm. Sometimes the term " GAMETOGENESIS " is used instead of meiosis. Scientists love vocabulary (sorry).

You can see from the p-square that any time you cross two hybrids, 3 of the 4 boxes will produce an organism with the dominant trait (in this example "TT", "Tt", & "Tt"), and 1 of the 4 boxes ends up homozygous recessive, producing an organism with the recessive phenotype ("tt" in this example).

Ma-Ma-Ma-Ma-Mendel's Third Law

The Law of Independent Assortment
Alleles for different traits are distributed to sex cells (& offspring) independently of one another.

OK. So far we've been dealing with one trait at a time. For example, height (tall or short), seed shape (round or wrinkled), pod color (green or yellow), etc. Mendel noticed during all his work that the height of the plant and the shape of the seeds and the color of the pods had no impact on one another. In other words, being tall didn't automatically mean the plants had to have green pods, nor did green pods have to be filled only with wrinkled seeds, the different traits seem to be inherited INDEPENDENTLY.

Please note my emphasis on the word "different". Nine times out of ten, in a question involving two different traits, your answer will be "independent assortment". There is a big ugly punnet square that illustrates this law so I guess we should take a look at it. It involves what's known as a "dihybrid cross", meaning that the parents are hybrid for two different traits.

The genotypes of our parent pea plants will be: RrGg x RrGg where
"R" = dominant allele for round seeds
"r" = recessive allele for wrinkled seeds
"G" = dominant allele for green pods
"g" = recessive allele for yellow pods

Notice that we are dealing with two different traits: (1) seed texture (round or wrinkled) & (2) pod color (green or yellow). Notice also that each parent is hybrid for each trait (one dominant & one recessive allele for each trait).

We need to "split" the genotype letters & come up with the possible gametes for each parent. Keep in mind that a gamete (sex cell) should get half as many total letters (alleles) as the parent and only one of each letter. So each gamete should have one "are" and one "gee" for a total of two letters. There are four possible letter combinations: RG, Rg, rG, and rg. These gametes are going "outside" the p-square, above 4 columns & in front of 4 rows. We fill things in just like before --- "letters from the left, letters from the top". When we finish each box gets four letters total (two "are's" & two "gees").

This is what it looks like:
RG Rg rG rg
rg RrGg

The results from a dihybrid cross are always the same:
9/16 boxes (offspring) show dominant phenotype for both traits (round & green),
3/16 show dominant phenotype for first trait & recessive for second (round & yellow),
3/16 show recessive phenotype for first trait & dominant form for second (wrinkled & green), &
1/16 show recessive form of both traits (wrinled & yellow).

So, as you can see from the results, a green pod can have round or wrinkled seeds, and the same is true of a yellow pod. The different traits do not influence the inheritance of each other. They are inherited INDEPENDENTLY.

Interesting to note is that if you consider one trait at a time, we get "the usual" 3:1 ratio of a single hybrid cross (like we did for the LAw of Segregation). For example, just compare the color trait in the offspring 12 green & 4 yellow (3:1 dominant:recessive). Same deal with the seed texture 12 round & 4 wrinkled (3:1 ratio). The traits are inherited INDEPENDENTLY of eachother --- Mendel's 3rd Law.

I would like to summarize Mendel's Laws by listing the cross that illustrates each.
tall x short
100% Tt
tall x tall
75% tall
25% short
round & green x round & green
9/16 round seeds & green pods
3/16 round seeds & yellow pods
3/16 wrinkled seeds & green pods
1/16 wrinkled seeds & yellow pods

Review Questions

1. Which cross would best illustrate Mendel's Law of Segregation?

Base questions #4-8 on the following information:

9. Crossing two dihybrid organisms results in which phenotypic ratio?

A. cD
B. Ee
D. ee


Back to Biology Topics Outline


Vocabulary Term Review Questions - CORRECT ANSWERS ARE UNDERLINED

1. Which of the following is a possible abbreviation for a genotype?

Review Questions - ANSWERED & EXPLAINED

1. Which cross would best illustrate Mendel's Law of Segregation?

Base questions #4-8 on the following information:

4. Which phenotype is dominant? white
5. What are the genotypes of the original parent plants? WW (pure white) x ww (pink)
6. What is the genotype of all the F1 offspring? Ww (white)
7. What would be the percentages of genotypes & phenotypes if one of the white F1 plants is crossed with a pink-flowered plant?

50% heterozygous white & 50% homozygous recessive pink.

The cross for this question would be "Ww (white F1) x ww (pink)".
The alleles of the white parent are above the columns & those of the pink parent are in front of the rows. 2 of 4 boxes (50%) are "Ww", which is heterozygous & would have the dominant trait (white). The other 2 of 4 boxes (50%) are "ww", which is homozygous recessive & would have the recessive trait (pink).

8. Which of Mendel's Laws is/are illustrated in this question? Dominance is illustrated by the original cross (WW x ww).

9. Crossing two dihybrid organisms results in which phenotypic ratio?

A. cD
B. Ee- a possible allelic pair but NOT SHOWN IN THE DIAGRAM, so this CAN'T be an answer
D. ee - an "allelic pair" is always two forms of the same letter. In this example they are two lowercase "e's".

Part 3: Ribophagy and Nucleotide Recycling

00:00:07.29 My name is David Sabatini.
00:00:09.12 I'm a member of the Whitehead Institute
00:00:10.27 and the MIT Department of Biology,
00:00:12.18 as well as Howard Hughes Medical Institute
00:00:14.11 and the Koch and Broad Institutes.
00:00:17.00 And in the third of a series of three lectures
00:00:19.19 in which I'm discussing the regulation of growth
00:00:21.18 by the mTOR protein kinase
00:00:23.29 and the pathways associated with it,
00:00:25.27 I'm gonna discuss with you today
00:00:28.02 ribophagy and its regulation by the mTOR pathway
00:00:31.07 and the recycling of nutrients, in particular nucleotides.
00:00:34.03 We now appreciate that ribosomes
00:00:35.28 contain a large fraction of the amino acids and nucleotides in the cell,
00:00:39.08 and so therefore they serve as a resource for the cell
00:00:42.02 to liberate them when it needs them,
00:00:44.00 particularly under conditions of starvation.
00:00:46.25 mTORC1, we now appreciate,
00:00:49.04 is one of the central regulators of growth,
00:00:51.07 linking the availability of nutrients in the environment
00:00:53.17 to whether a cell and an organism
00:00:55.14 is in an anabolic or catabolic state,
00:00:57.08 and ribophagy would be an example of a catabolic process.
00:01:01.03 The story here really begins
00:01:03.09 with our efforts to understand mTORC1 biology,
00:01:05.01 in particular how it senses the diversity of upstream signals,
00:01:09.00 which are indicated here, that the pathway can detect.
00:01:11.02 What are the sensors for these signals?
00:01:13.19 How are these signals integrated into a coherent output
00:01:15.23 that then can talk directly to mTORC1,
00:01:17.19 which can then regulate cell growth
00:01:20.00 and eventually cell division?
00:01:22.11 So, to tell you this story, I need to tell you a little bit about,
00:01:24.16 in particular, how the pathway senses amino acids
00:01:27.07 and give you a little bit of background on how this happens.
00:01:30.19 For us, the story started, really,
00:01:32.06 with images such as this,
00:01:33.29 in this case a video, in which what you're looking at are cells
00:01:37.14 that have been starved of amino acids.
00:01:39.03 And you're looking at the localization of this mTORC1 protein complex.
00:01:42.08 And what you can see is it's in this diffuse pattern in the cytosol.
00:01:44.25 The black areas here are the nuclei
00:01:46.25 of these two human cells.
00:01:48.24 And when I start the video,
00:01:50.28 a white box will emerge, which indicates where we've added amino acids.
00:01:53.15 And what you can see happens is that, very rapidly,
00:01:56.19 mTORC1 moves to certain localizations in the cell --
00:01:59.08 punctae in the cell.
00:02:00.20 These turn out to be lysosomes,
00:02:02.14 and mTORC1 moves there when the pathway is activated,
00:02:04.15 and it comes off the lysosomes
00:02:06.25 when the pathway is inactivated.
00:02:09.03 This, as I discussed in my second lecture,
00:02:11.00 led to quite a bit of interest in the lysosome
00:02:13.26 as a signaling organelle,
00:02:15.21 and you'll see some of that in this lecture as well.
00:02:17.20 This led us to propose a model
00:02:20.04 in which the translocation is one part
00:02:22.11 of a coincidence detector.
00:02:24.12 It's mediated by these interesting GTPases
00:02:26.05 called the Rag GTPases,
00:02:28.03 which are heterodimeric,
00:02:29.16 and in fact they form the binding site, the docking site,
00:02:31.17 on the lysosomal surface for mTORC1.
00:02:33.20 The second part of the coincidence detector
00:02:35.20 is a different GTPase called the Rheb GTPase.
00:02:38.04 And its activity is regulated by growth factors
00:02:40.14 as well as energy sources,
00:02:42.03 which here I'm exemplifying by insulin.
00:02:44.08 You need both of these inputs for mTORC1 to be activated.
00:02:48.27 One puts mTORC1 in the right place,
00:02:51.12 and the other one turns on its activator, Rheb.
00:02:53.25 If we go into a little bit more detail, here,
00:02:55.15 what we propose is that nutrients mediate the translocation
00:02:59.02 -- here, I'm giving you the example of amino acids,
00:03:00.26 but glucose would do the same thing.
00:03:02.14 We've identified lysosome-associated complexes
00:03:04.20 that mediate the sensing,
00:03:07.16 for example the inside-out sensing,
00:03:09.04 as well as the placement of Rheb
00:03:11.23 on the lysosomal surface.
00:03:13.10 And what's known upstream?
00:03:14.23 We haven't worked much on upstream of what's. Rheb,
00:03:16.23 but there's a whole disease-associated complex
00:03:18.24 called the tuberous sclerosis complex,
00:03:20.09 which is connected to a number of different diseases.
00:03:22.10 In addition, there's a whole cytosolic sensing.
00:03:24.24 branch to the sensing arm,
00:03:26.20 which I won't discuss too much here,
00:03:28.05 but I did discuss in my second lecture.
00:03:30.09 One of the things that we've been particularly interested in.
00:03:32.13 what are the sensors for this pathway?
00:03:34.11 None of these protein turn out to be sensors,
00:03:35.29 or none of these protein complexes, I should say,
00:03:38.03 are the sensor.
00:03:39.17 And the first one we identified
00:03:41.11 was the sensor for the inside of the lysosome,
00:03:43.14 which we now know is a lysosomal arginine sensor
00:03:45.22 that we call SLC38A9.
00:03:47.29 This a protein of unknown function
00:03:50.09 that seems to act in sensing and transmitting arginine levels
00:03:53.11 across the lysosomal membrane.
00:03:56.12 In addition, we identified cytosolic sensors
00:03:58.26 for arginine as well as for leucine,
00:04:01.10 and a sensor for methionine,
00:04:03.09 which works through the intermediate S-adenosylmethionine, or SAM.
00:04:07.13 So, you can see there are a variety of different sensors for this pathway.
00:04:10.13 Now, I have to say, the cytosolic sensors
00:04:12.21 are rather simple proteins.
00:04:14.05 They bind to one of these complexes in the cytosol
00:04:16.12 in the absence of their cognate ligand.
00:04:18.18 When the ligand binds to them,
00:04:20.12 they have a conformational change and they fall off.
00:04:22.15 When they're bound, they typically either repress or activate
00:04:26.02 the complex to which they're bound.
00:04:27.23 The transmembrane sensor, the SLC38A9,
00:04:30.08 is a much more complicated protein.
00:04:31.21 It's a much larger protein.
00:04:33.06 It has 11 transmembrane domains,
00:04:34.26 and it also lives at this very interesting interface
00:04:37.16 between the inside of the lysosome and the cytosol.
00:04:40.18 And so, we always imagined that this protein
00:04:42.26 probably does other things
00:04:45.01 besides simply acting as an arginine sensor
00:04:47.18 for this pathway.
00:04:49.20 However, we had a challenge,
00:04:51.12 and the challenge was that probably whatever it did
00:04:53.12 was happening inside the lysosome.
00:04:55.02 And lysosomes are a small fraction
00:04:57.14 of the total volume of a human cell.
00:04:59.05 In the cells that we've looked at,
00:05:00.25 they're typically around 2% of that volume.
00:05:02.22 So, if something's happening in the lysosome,
00:05:04.17 you're not gonna really see it reflected
00:05:06.20 at the level of the whole cell.
00:05:08.18 So, one of the efforts that we've had going on the lab now
00:05:10.29 for a number of years
00:05:12.25 is to develop methods to very rapidly
00:05:15.02 purify a particular organelle,
00:05:16.26 and that the methods be compatible with metabolite profiling,
00:05:19.07 that is, the quantitation of small molecules in that organelle.
00:05:22.18 We first got this to work for mitochondria.
00:05:24.13 Mitochondria are a lot easier, though,
00:05:25.27 because they're about 10-15% of cell volume.
00:05:28.26 And more recently, we've developed a method
00:05:31.19 -- we call it the Lyso-IP method --
00:05:33.12 for looking at metabolites inside the lysosome.
00:05:36.25 The method is conceptually very simple.
00:05:38.27 You simply express a protein in cells
00:05:41.23 that goes to the lysosomal membrane
00:05:43.21 and has a tag, in this case this 3xHA tag.
00:05:45.22 And then, through a series of steps,
00:05:47.21 we break open the cell and isolate with a magnet -- magnetic beads --
00:05:51.05 these organelles.
00:05:53.04 It's conceptually simple, but in practice quite hard.
00:05:56.09 It took us about a year and a half to two years
00:05:57.23 to actually get this to work.
00:05:59.03 There's lots of little tricks along the way.
00:06:00.17 But as soon as it did work, it worked very well,
00:06:02.26 and we knew that it worked well
00:06:05.01 because we had a little trick that we could do.
00:06:07.07 To validate that our method for looking at lysosomal metabolites was working,
00:06:10.24 what we did is we treated cells
00:06:12.20 with two different inhibitors of the vacuolar ATPase.
00:06:15.12 And this is the enzyme which the lysosome
00:06:18.08 uses to acidify the lumen of the lysosome,
00:06:19.26 which is typically somewhere around pH 4.5.
00:06:22.10 And that pH gradient between the lumen and the cytosol
00:06:25.10 is very important for the lysosome to do many things,
00:06:27.07 for example transport molecules in and out of the lysosome.
00:06:30.16 And if you look at this heat diagram here,
00:06:33.06 this sort of clustergram,
00:06:35.00 at the first two columns,
00:06:36.21 what you're looking at is whole cell samples
00:06:38.24 treated with these two different inhibitors,
00:06:40.12 and you can see there's very few changes.
00:06:42.04 Each horizontal line is a metabolite.
00:06:44.14 And this is because the lysosome accounts for a small fraction
00:06:46.29 of the total cell volume,
00:06:48.16 and therefore you don't see many changes
00:06:50.09 when you just perturb the lysosome.
00:06:51.26 In contrast, in the third and fourth columns,
00:06:54.10 which represent the lysosomal samples here,
00:06:56.05 there's really dramatic changes --
00:06:58.15 mostly metabolites going up, very highly,
00:07:00.23 inside the lysosome when we inhibit the V-ATPase.
00:07:03.17 This is best seen in this principal component analysis
00:07:05.23 where, again, the whole cell samples all cluster together,
00:07:08.25 whether they've been treated with a vehicle
00:07:10.24 or the V-ATPase inhibitors,
00:07:12.07 while the two V-ATPase inhibitors
00:07:14.12 are clearly distinct from the whole cell sample
00:07:16.08 when we look inside of the lysosome.
00:07:20.05 So, using this method, then,
00:07:21.29 we did a very simple experiment
00:07:23.24 where we knocked out this SLC38A9 arginine sensor
00:07:27.06 and looked at the inside of the lysosomes
00:07:29.07 under those knockout conditions.
00:07:33.04 And we were quite surprised to see what we found.
00:07:35.11 We found that most essential hydrophobic amino acids
00:07:37.27 went up dramatically inside the lysosome.
00:07:40.20 And the conclusion that we eventually drew was that
00:07:44.04 this protein is not only an arginine sensor,
00:07:45.28 but it's also a transporter
00:07:48.17 for these key, essential amino acids,
00:07:50.11 and that this transport function
00:07:52.14 is also regulated by arginine.
00:07:53.27 So, arginine turns out to have this interesting
00:07:56.08 lysosomal signaling role.
00:07:58.00 It turns on mTORC1
00:07:59.24 and at the same time it releases from lysosomes
00:08:02.07 the amino acids that mTORC1 needs to drive anabolism,
00:08:04.19 because these are essential amino acids
00:08:07.12 that the cell then needs to use. to do. use protein.
00:08:09.10 to do protein synthesis.
00:08:11.19 And so, we asked ourselves, well, why,
00:08:15.18 you know, is there this arginine sensor here
00:08:17.12 and there's also one in the cytosol?
00:08:18.28 What might be the conditions under which cells
00:08:20.25 care about this arginine sensor?
00:08:22.19 Well, it turns out that many cells don't obtain their free.
00:08:25.05 their amino acids from. in a free form,
00:08:27.13 that is, floating around in the plasma
00:08:30.12 or, in the case of cells in culture, in the media,
00:08:32.29 and then coming into the cell.
00:08:34.10 Rather, what they do is they take up protein,
00:08:36.14 put it into the lysosome, and break that protein down
00:08:38.29 and release amino acids.
00:08:40.12 And it turns out in cells like those
00:08:42.22 -- pancreatic cancer cells being probably the best example of those --
00:08:45.04 this pathway is absolutely essential for cells to grow
00:08:48.24 when you need to feed them protein
00:08:50.26 for them to be able to grow and proliferate.
00:08:53.16 And so, one of the experiments we did is
00:08:55.16 we knocked out this gene and we asked,
00:08:57.11 can we make a pancreatic tumor?
00:08:59.01 And the answer is no.
00:09:00.15 So, if we take pancreatic cancer cells, knock out SLC38A9,
00:09:02.00 add back a control gene,
00:09:04.12 you can see that we don't get tumors.
00:09:06.03 This is tumor volume on the y axis.
00:09:07.20 If we add back the wild type form, we do.
00:09:11.00 Now, you saw that protein was sort of embedded
00:09:13.18 in the middle of a number of other complexes.
00:09:15.24 How do we know it's not a structural role
00:09:17.26 versus a transport role?
00:09:19.11 Well, we identified a mutant, this T133W mutant,
00:09:22.27 which has no transport activity,
00:09:25.07 and you see also we cannot make tumors
00:09:27.15 when cells like pancreatic cancer cells express that mutant.
00:09:31.07 This is quite exciting,
00:09:33.11 because it turns out that the pancreatic cancer cells
00:09:35.05 mostly are driven by mutations in Ras,
00:09:36.29 which has turned out to be largely undruggable,
00:09:39.08 although there are. there is progress in that space.
00:09:41.10 And so, this could be a way of specifically
00:09:43.13 targeting these types of cancer cells,
00:09:45.04 because most cancer cells actually don't.
00:09:46.19 or, most normal cells don't use this pathway
00:09:48.09 as a way of obtaining amino acids.
00:09:51.18 So, one of the more common questions that I get,
00:09:53.14 and something that we've thought quite a bit about, is,
00:09:55.27 why does the mTORC1 pathway
00:09:58.03 sense lysosomal arginine?
00:09:59.29 And I should say also, lysine levels,
00:10:01.11 which we have some evidence for,
00:10:02.20 but I haven't discussed here.
00:10:04.14 Why did nature evolve to want to know
00:10:06.21 about the presence or absence of arginine inside of the lysosome?
00:10:10.04 Now, because this lysosomal branch
00:10:13.09 of the nutrient sensing pathway
00:10:15.21 seems to be particularly important for when the pathway
00:10:17.23 is detecting amino acids coming from the breakdown of proteins,
00:10:21.11 it made sense to ask, well,
00:10:23.13 which proteins have a lot of lysine and arginine?
00:10:25.19 And so, what we did is we analyzed
00:10:27.15 the Uniprot data set for human proteins
00:10:31.28 and their fraction of lysine and arginine.
00:10:34.12 And I should say, there's about 30,000 or so
00:10:37.12 entries into the data set,
00:10:38.23 because there's isoforms.
00:10:40.05 And the results were quite striking,
00:10:41.22 because what we found is that many ribosomal proteins
00:10:43.19 were very high in lysine and arginine.
00:10:45.13 In fact, there are some -- you can see the one at the top, there --
00:10:48.09 that was about 70% lysine and arginine.
00:10:51.28 Now, in some ways, this is not so surprising,
00:10:53.25 because these are RNA binding proteins
00:10:55.14 and RNA is acidic,
00:10:57.03 and you might imagine that it would bind to basic proteins,
00:10:59.25 and arginine and lysine are very basic.
00:11:01.21 But what's important to keep in mind is that
00:11:04.28 the majority of the protein in the cells
00:11:08.16 is actually in ribosomes, and this means, therefore,
00:11:11.18 that the majority of lysine and arginine
00:11:13.11 is going to be particularly inside of ribosomes.
00:11:15.12 And so, this led to the question, then,
00:11:18.04 does arginine in lysines. in lysosomes
00:11:21.07 signal the degradation of ribosomes to the mTORC1 pathway?
00:11:23.05 Is that why it's sensing arginine,
00:11:25.19 and to a lesser extent lysine,
00:11:27.09 because it wants to know if the pathway is degrading ribosomes?
00:11:30.06 This is quite challenging to test.
00:11:31.25 What you need to be able to do is to block, specifically, this degradation.
00:11:34.26 This degradation would be termed ribophagy.
00:11:36.25 This is what it's been termed in yeast.
00:11:38.12 We'd need to find, presumably, an adaptor protein
00:11:40.25 that we require to bring the ribosomes to the autophagosome
00:11:44.17 and eventually to the lysosomes
00:11:46.09 and be able to block this step.
00:11:48.20 Now, in our hands, we see very clear evidence of ribosome breakdown
00:11:52.17 in response to starvation,
00:11:54.05 either by amino acids or other nutrients
00:11:55.28 or by mTORC1 inhibition.
00:11:57.18 And you can see here. these are wild type cells,
00:11:59.12 and you can see ribosomal proteins dropping over time --
00:12:02.00 really, at 8 hours is where you start to see the most significant effects.
00:12:04.24 These are three different ribosomal proteins.
00:12:07.12 We can also look at ribosomal RNA,
00:12:09.06 and as I'll show you later on,
00:12:10.17 we can also look at different metabolites as indicators.
00:12:15.14 Now, this process is completely dependent on autophagy.
00:12:18.15 If we knock out a key autophagy gene,
00:12:20.02 you can see that it no longer happens.
00:12:22.21 You can see the knockout here.
00:12:24.07 This is an indicator of mTORC1 activity,
00:12:26.04 this S6 kinase phosphorylation.
00:12:29.23 We reasoned that a protein involved in ribophagy
00:12:32.10 would end up in the lysosome
00:12:34.07 under starvation conditions or mTOR inhibition conditions,
00:12:37.04 and so what we did is we modified
00:12:40.19 our method for isolating lysosomes
00:12:42.08 that we use for metabolite profiling
00:12:43.28 for looking at proteins.
00:12:45.12 What you're looking at here is every single dot
00:12:46.27 is a protein,
00:12:48.11 and those that come off the diagonal
00:12:50.20 are proteins that either with amino acid starvation, nutrient starvation,
00:12:53.25 or mTOR inhibition are coming on and off the lysosome.
00:12:57.19 We knew that this had worked quite well
00:12:59.02 because if we look at the three proteins that make up mTORC1,
00:13:01.24 they're very nicely regulated.
00:13:03.15 In fact, they're very close to each other
00:13:04.26 and behaving exactly as we knew they would.
00:13:07.08 There are other complexes shown in color.
00:13:08.25 different colors here, that are also behaving exactly as they would.
00:13:12.05 In fact, this data set has become an important one in the lab
00:13:14.20 for people interested in dynamic proteins on the lysosome.
00:13:18.22 Now, these are not the proteins
00:13:20.23 that we ended up focusing on in this study.
00:13:22.13 Instead, what we focused on were these two different proteins, here.
00:13:25.25 Greg Wyant, who is one of the people who led this project,
00:13:29.25 instead focused on these two proteins
00:13:31.29 that I had never heard about before.
00:13:33.13 One is called NUFIP1 and the other one's called ZH. ZNHIT3 --
00:13:37.24 ZN-HIT3.
00:13:39.22 And you can see what those proteins stand for.
00:13:41.13 And when I asked him why he picked these proteins,
00:13:43.03 he said, well, he found it was odd that NUFIP1,
00:13:45.06 which you can see has nuclear in its name,
00:13:47.02 would be at the lysosome.
00:13:48.20 It was supposed to be a nuclear protein.
00:13:50.03 In addition, it was thought to interact with this fragile X mutant protein,
00:13:53.11 FMRP,
00:13:55.05 and it has been connected to ribosomes.
00:13:57.11 So, there was an interesting connection there.
00:13:59.07 So, if you look at the levels of these proteins
00:14:01.23 in cells that have either been starved of amino acids
00:14:04.06 or treated with this mTOR inhibitor,
00:14:06.22 as well as a whole variety of markers of different organelles,
00:14:09.03 including lysosomes, ER, Golgi, and peroxisomes,
00:14:11.21 you can see these proteins don't change levels at all.
00:14:14.01 Nothing happens at the whole cell level.
00:14:16.26 But if you look at the lysosomes, with this method, the Lyso-IP method,
00:14:20.19 you can see that the levels of both of these
00:14:23.09 go up dramatically.
00:14:24.19 This was interesting because these are known to be obligate heterodimers.
00:14:27.27 These two proteins interact together.
00:14:29.10 And in fact, if you lose one,
00:14:31.11 you lose the other.
00:14:32.13 They seem to also be important for their stability.
00:14:34.10 So, this was interesting.
00:14:35.28 Now, the fact that the levels of the whole cell lysate
00:14:38.11 don't change,
00:14:39.29 but the levels of the lysosome go up,
00:14:41.27 means that there has to be a movement of this protein
00:14:44.03 from some compartment to another.
00:14:46.13 It's the only way you could explain this.
00:14:48.15 And indeed, NUFIP1 is a. is a nuclear protein,
00:14:52.07 as you can see here on the left side.
00:14:54.06 However, it's a nuclear protein in unstarved cells,
00:14:57.10 or un-mTOR-inhibited cells.
00:14:59.04 When you inhibit mTOR, it moves, now,
00:15:02.02 to a compartment that overlaps with LAMP2,
00:15:05.00 which is a classic lysosomal marker.
00:15:07.07 So, I'm showing you this here, now, in these immunofluorescence images,
00:15:11.00 but we can also do the same kind of experiments
00:15:12.22 using cell fractionations.
00:15:14.29 So, the conclusion here is that
00:15:17.05 upon starvation or mTOR inhibition,
00:15:18.14 NUFIP moves from the nucleus to the lysosome.
00:15:24.06 Another reason that Greg became interested in NUFIP
00:15:26.20 is that when he looked at its sequence,
00:15:28.09 it was clear that it had a series of what are called LIR motifs.
00:15:31.06 These are very simple motifs
00:15:34.07 that are known to bind LC3B.
00:15:36.09 LC3B is a very interesting protein.
00:15:38.03 It's a protein that decorates the autophagosome.
00:15:40.27 Remember the autophagosome is what's gonna engulf cellular contents
00:15:44.07 and degrade them once it fuses with the lysosome.
00:15:46.26 LC3B decorates that autophagosomal membrane
00:15:52.01 and acts as a docking site to bring things to it.
00:15:54.13 He noticed that NUFIP had several LIR motifs.
00:15:58.02 And so, he asked, does it bind LC3B?
00:16:00.08 And indeed, it does.
00:16:01.24 You can see here, compared to a control protein,
00:16:03.13 it binds very well.
00:16:04.22 In fact, it won't even bind to a related protein
00:16:06.29 called GABARAP, which is quite similar to LC3B.
00:16:10.11 More importantly, though,
00:16:12.10 we could show that one of these LIR motifs
00:16:14.08 mattered for the binding, the second one. Y
00:16:16.26 ou can see that if you mutate it
00:16:18.18 -- that W40A mutation --
00:16:20.11 we eliminate the binding completely.
00:16:23.10 So, this led to the idea that the reason that NUFIP
00:16:27.10 was ending up on lysosomes
00:16:29.00 was that it was coming bound to autophagosome,
00:16:31.10 or in autophagosomes.
00:16:32.24 And indeed, if we knock out the autophagosomal pathway,
00:16:35.21 if we knock out LC3B,
00:16:37.11 or if we knock out NUFIP
00:16:39.11 and then put this mutant that can't bind LC3B,
00:16:41.12 NUFIP doesn't go to the lysosome at all.
00:16:43.10 It's completely clean.
00:16:44.25 It doesn't show up in that compartment.
00:16:48.26 In other data, we were able to show that
00:16:51.28 NUFIP can interact with ribosomes,
00:16:53.10 both inside of cells as well as in vitro.
00:16:55.14 And the model that we originally developed
00:16:57.05 is that NUFIP is a protein that cycles
00:17:00.14 in and out of the nucleus.
00:17:01.24 In fact, it has a nuclear localization signal
00:17:03.05 and a nuclear export signal,
00:17:04.28 and we can play with either of those
00:17:06.15 and perturb the protein in the appropriate way.
00:17:09.11 The data that we had was that
00:17:12.16 when you starve cells or you treat them
00:17:14.00 with an mTOR inhibitor,
00:17:15.20 the ribosome acquires some mark,
00:17:17.07 indicated by this blue star here.
00:17:19.25 And this mark allows NUFIP to bind to the ribosome.
00:17:23.03 Now, you should ask, why?
00:17:24.19 Why do we think this?
00:17:25.27 Well, the reason we do is that
00:17:27.15 we can purify ribosomes from starved or unstarved cells,
00:17:31.15 and we can purify NUFIP from starved or unstarved cells,
00:17:34.16 and we can mix them then in vitro.
00:17:36.28 And we only get a good interaction
00:17:39.07 if NUFIP comes from starved or mTOR-inhibited cells.
00:17:42.15 The state. sorry, the ribosome
00:17:45.01 comes from starved or mTOR-inhibited cells.
00:17:47.11 The state of NUFIP itself does not matter.
00:17:50.17 We think, then, this traps NUFIP into the.
00:17:53.23 into the cytosol, and then it can interact with LC3B.
00:17:55.22 And when we do equivalent experiments
00:17:57.02 looking at the LC3B-NUFIP interaction,
00:17:59.00 we actually don't find any regulation of that interaction.
00:18:02.00 We find that that's just regulated by the localization of NUFIP.
00:18:06.07 So, the question then became,
00:18:07.16 well, is this process important
00:18:09.05 for the breakdown of ribosomes by ribophagy?
00:18:11.15 Is ribophagy at play here?
00:18:14.20 Well, indeed it is.
00:18:16.17 If we knock out NUFIP -- so, we have NUFIP-null cells,
00:18:18.10 and those are those first two lanes --
00:18:19.29 you can see that when we starve them of amino acids,
00:18:21.23 these marker ribosomal proteins don't change.
00:18:24.25 When we add back wild type NUFIP,
00:18:26.23 in the sec. the third and fourth lanes,
00:18:28.28 you can see now that when we starve them,
00:18:30.20 ribosomal proteins go down.
00:18:32.20 And very gratifyingly, if we put in that mutant
00:18:34.24 they can't bind to LC3B,
00:18:36.18 it looks like the knockout cells.
00:18:40.08 So, this is done by looking at ribosomal proteins.
00:18:43.04 We can also look at ribosomal RNA.
00:18:45.12 But really, the classic approach for looking at ribophagy
00:18:48.08 would be to look at ribosomes
00:18:50.03 via transmission electron microscopy, by EM.
00:18:52.18 And in fact, that first picture on my opening slide
00:18:55.19 is an EM of ribosomes inside an autophagosome.
00:18:59.03 And indeed, if you knock out NUFIP,
00:19:00.29 we don't find ribosomes in the.
00:19:02.28 this leftmost panel inside autophagosomes.
00:19:05.23 If we add it back, we do.
00:19:07.16 And if we add back the mutant, we see very few.
00:19:10.10 Now, you could say, well, David,
00:19:12.18 this just says that NUFIP is important for autophagy.
00:19:15.13 Right?
00:19:17.09 There's no distinction between its role in ribosome breakdown.
00:19:20.00 between the breakdown of anything else.
00:19:21.25 But we have looked at a number of other substrates
00:19:24.08 for what's called selective autophagy,
00:19:25.28 where the cell doesn't break down everything,
00:19:27.14 but it's breaking down select compartments
00:19:29.00 or select complexes.
00:19:31.00 For example, if we look at ferritin,
00:19:32.21 NUFIP has no role in the breakdown of this,
00:19:34.20 while we know that ferritin is broken down
00:19:36.25 by a selective autophagy pathway.
00:19:39.00 Likewise, we can look at the breakdown of mitochondria.
00:19:40.29 Again, we don't see any role for it in that process.
00:19:45.03 Now, if I go back to the first hypothesis we had --
00:19:50.06 ribophagy is gonna be important for the production
00:19:52.15 of arginine inside the lysosome,
00:19:54.08 and therefore the sensing of arginine
00:19:55.27 by the mTORC1 pathway --
00:19:58.04 is this at all true?
00:20:00.24 Well, the way we do arginine sensing is shown here,
00:20:02.07 in those first two lanes.
00:20:03.15 We starve cells for arginine
00:20:04.27 for about 50 minutes
00:20:06.12 and then we add back arginine
00:20:08.09 for 10 minutes.
00:20:09.16 And if you look at a marker of pathway activity, S6 kinase,
00:20:11.04 you can see it's nicely regulated.
00:20:13.13 What is far less known.
00:20:15.11 and this is well known by many people.
00:20:17.04 what is far less known, though,
00:20:19.16 is that if you starve cells for longer periods of time
00:20:21.26 -- not 50 minutes but rather hours --
00:20:24.16 even in the absence of arginine,
00:20:26.13 the pathway reactivates.
00:20:28.07 And the reason that it reactivates
00:20:30.18 is because the cell does autophagy,
00:20:31.28 degrades its own protein,
00:20:33.27 and releases arginine.
00:20:35.15 This is completely dependent on autophagy.
00:20:37.17 If we knock out the autophagy pathway,
00:20:39.11 this reactivation doesn't happen.
00:20:41.03 The first two lanes are identical.
00:20:43.11 The second half of these blots.
00:20:45.29 there's no activity at all.
00:20:47.19 So, does NUFIP matter for this?
00:20:49.15 And again, very satisfyingly, it does.
00:20:51.19 You can see that if we knock it out,
00:20:54.12 it doesn't completely suppress this
00:20:55.24 -- autophagy would completely eliminate it --
00:20:57.26 but it strongly suppresses it,
00:20:59.13 arguing that in fact ribophagy is important for the production of the arginine
00:21:02.25 that is then sensed for this pathway,
00:21:04.11 and suggesting why then maybe
00:21:07.08 the pathway would evolve to detect arginine
00:21:09.17 in the lysosome.
00:21:11.10 So, is this the whole story?
00:21:12.21 We don't think so, because while the ribosome accounts for 50%
00:21:17.26 of the protein inside of a cell,
00:21:19.08 it accounts from a much larger fraction of the nucleotides,
00:21:22.07 in this case the ribonucleotides
00:21:24.03 that make up RNA.
00:21:25.12 80% is estimated in human cells.
00:21:27.13 In yeast, it's estimated to be 95%.
00:21:31.17 Remembering this reminded us of an experiment
00:21:34.07 we had done that we hadn't paid too much attention to.
00:21:35.22 And that is when we gave
00:21:38.00 this very potent and strong mTOR inhibitor called Torin,
00:21:40.24 what we noticed is that many nucleosides
00:21:43.16 went up inside the cell, quite dramatically.
00:21:47.01 That's the bar graphs shown here,
00:21:48.28 the black ones in wild type cells.
00:21:51.09 And that this increase was dependent on the autophagy pathway.
00:21:55.13 In the red bars,
00:21:57.17 we've knocked out a core autophagy gene.
00:21:58.17 This doesn't happen anymore.
00:22:00.11 Incidentally, there's inosine here
00:22:02.12 because the lysosome deaminates adenosine to make inosine.
00:22:04.20 That's why there's so much inosine
00:22:06.17 that you see here
00:22:08.07 So, if the ribosome contains a large fraction
00:22:11.10 of the RNA,
00:22:12.22 and NUFIP is required for breakdown
00:22:15.22 of the ribosome in the lysosome,
00:22:17.26 knocking it out should have an impact as well.
00:22:20.13 And indeed, it does.
00:22:22.09 Not as great as knocking out autophagy,
00:22:24.12 because there are other particles that contain RNA, such as P granules,
00:22:27.08 that are also degraded through the autophagy pathway.
00:22:31.11 However, we had a little trick that we could do,
00:22:33.00 and that is that we know that there are many modified bases
00:22:37.15 on ribosomal RNA,
00:22:40.04 particularly pseudouridine and 1-methyladenosine.
00:22:42.19 These are. these are bases
00:22:44.16 that are ribonucleoside bases
00:22:46.10 that are modified slightly.
00:22:47.24 And the majority of these are in the ribosomal RNA
00:22:50.08 or on tRNAs.
00:22:51.26 And so, we might expect that knocking out NUFIP
00:22:53.20 would completely prevent the increase in these.
00:22:57.01 And that's the case: here are two of them,
00:22:59.05 here, pseudouridine and 1-methyladenosine.
00:23:02.11 These behave differently than those other ribonucleosides
00:23:05.17 that can be found in other RNAs
00:23:07.05 besides rRNA and tRNA.
00:23:09.11 I should say, these modified ones can be found on other RNAs too,
00:23:11.21 but at much, much lower levels.
00:23:14.18 So, one of the classic phenotypes of cells
00:23:16.22 lacking the traditional autophagy pathway
00:23:19.06 is that they're sensitive to starvation conditions.
00:23:21.11 And in mammalian cells,
00:23:22.29 this is typically done by putting cells
00:23:24.26 into what's called Hanks' balanced salt solution.
00:23:27.09 As the name implies, this is a buffer that basically
00:23:30.07 has no nutrients in it.
00:23:31.16 And what wild type cells do,
00:23:32.29 which is the first little circle in this.
00:23:34.29 in this figure here,
00:23:37.00 is they basically hunker down and survive -- they don't die.
00:23:38.26 You're looking at a well from the top,
00:23:40.25 where we've stained the cells that you can see on the bottom.
00:23:43.05 However, if you knock out either of sort of two core autophagy genes
00:23:47.09 -- autophagy-5. ATG5 or ATG7 --
00:23:50.14 cells die.
00:23:51.24 So, this has been well known for a long period of time.
00:23:53.24 So, we wondered, well, what happens if we knock out
00:23:56.04 just the ribophagy pathway of the autophagy system
00:23:58.18 by knocking out NUFIP?
00:24:00.13 Indeed, we actually get exactly the same phenotype,
00:24:03.04 suggesting that the breakdown of ribosomes
00:24:05.18 is particularly important for the survival of cells
00:24:07.10 under starvation conditions.
00:24:10.01 A number of years ago, Eileen White had a remarkable paper
00:24:12.24 where she showed the survival of defect of autophagy-null cells
00:24:17.13 could be completely suppressed
00:24:19.20 by simply adding nucleosides to the media.
00:24:22.08 And you can see here, this --
00:24:24.09 we were able to replicate this very nicely --
00:24:25.29 suggesting that it's the nucleosides that are produced during riboph.
00:24:29.09 during autophagy that are important for the survival of the cells.
00:24:31.22 And consistent with that,
00:24:33.19 you can see that the loss of NUFIP
00:24:35.17 is also completely rescued by adding nucleosides to the media.
00:24:40.05 These data then suggest that in the autophagic breakdown
00:24:43.03 of cellular components,
00:24:44.18 it's really the ribosomes,
00:24:46.06 and in particular their RNA component,
00:24:48.20 and therefore the nucleosides,
00:24:50.06 which then can be converted nucleotides,
00:24:51.19 that matter the most.
00:24:54.20 This has led, therefore, to this type of model,
00:24:57.01 where starvation leads to the inhibition of mTORC1.
00:25:00.12 mTORC1 then regulates NUFIP
00:25:03.17 and the ribosome in a way
00:25:05.18 that allows NUFIP to bind the ribosome.
00:25:07.08 We think the regulation acts mostly at the level of the ribosome.
00:25:09.15 This induces ribophagy and the production of nucleosides,
00:25:12.07 and promotes the survival of cells
00:25:14.11 under these starvation conditions.
00:25:15.27 We think this fits under a larger theme,
00:25:17.16 when if you look back and say, well,
00:25:19.20 what are some of the core functions of mTORC1?,
00:25:21.02 we would argue it is in regulating
00:25:23.21 the balance between the production of ribosomes
00:25:25.26 -- ribosome biogenesis --
00:25:27.01 and the breakdown of ribosomes.
00:25:29.03 And indeed, you can imagine that what we're looking at here
00:25:31.24 is whether the cell wants the components of ribosomes
00:25:33.18 -- RNA and nucleotides --
00:25:35.17 to either be in this free form, as on the right side of this balance,
00:25:38.29 or in the polymeric form, as a ribosome.
00:25:43.14 And indeed, from this type of model,
00:25:44.28 you can think of the ribosomal as a storage compartment
00:25:46.13 for these types of nutrients inside the cell,
00:25:48.11 which otherwise there is none in the cell.
00:25:51.11 We have a number of questions that have emerged from this work.
00:25:53.09 For example, we'd like to know what is modified in the ribosome
00:25:56.01 that allows NUFIP to bind.
00:25:57.11 This is a very active area in the lab.
00:25:59.19 And moreover, we're very interested in this step
00:26:01.15 from ribophagy to the production of nucleosides.
00:26:03.10 Many things have to happen inside the lysosome
00:26:05.19 to produce the nucleosides,
00:26:07.20 and then from the nucleosides to be exported out,
00:26:09.16 and we think there are many interesting gene products
00:26:11.17 to study in that system.
00:26:13.07 This is the work, really,
00:26:14.29 of two very talented people in the lab:
00:26:16.20 Greg Wyant, who was a student,
00:26:18.06 and then Monther Abu-Remaileh, who was a postdoc.
00:26:20.00 They developed together the method for looking at lysosome metabolites
00:26:23.04 and lysosomal proteins,
00:26:25.26 and really collaborated on the ribophagy story I just told you about.
00:26:27.22 We also had tremendous collaboration
00:26:29.29 with Alessandro Ori in Germany,
00:26:31.04 who did the mass spectrometry
00:26:33.01 for looking at the lysosomal proteome,
00:26:34.12 as well as from the Whitehead Metabolomics Core,
00:26:36.20 which was led initially by Lisa Freinkman
00:26:38.15 and more recently by Caroline Lewis.
00:26:41.09 And you can see there, on the left,
00:26:43.13 a number of nutrient. a number of funding sources
00:26:45.14 that have helped our work,
00:26:47.19 some that we've had for a number of time and others,
00:26:49.05 such as the Lustgarten Foundation and the ACS Professorship,
00:26:53.06 which are more recent.
00:26:54.07 Thank you for paying attention,
00:26:55.20 and also thank you to iBio for giving me this opportunity to speak.

  • Part 1: Introduction to mTOR and the Regulation of Growth

Watch the video: Taylor applications: Physics (January 2022).