When did Adam Live? Part 3- Genetics

When did Adam Live? Part 3- Genetics

by Glenn R. Morton

This post is mostly for my young-earth-believing brothers and sisters in Christ.  Theistic evolutionists already accept much, but not all of what lies below.  This is the third in a series on my view of how to concord Scripture with science.  This, like the two posts below is preface to putting it all together, showing that if one is to have truth in the creation accounts, one must move Adam and Eve way back in time. The next and last preface will be a look at the fossil record and what it says about when early man arose. For now we will look at the vast evidence that requires Adam and Eve to have lived in the age of the small brained hominids. If you haven't read my post on ancient religion and on brain size, they can be found at the links in this sentence.

The area of genetics is one place where I think everyone misuses the results to get the answer they want.  Anthropologists act as if mitochondrial Eve, the oldest common mother of our mitochondria, defines the date of the origin of the H. sapiens.  They say H. sapiens speciated  about 200,000 years, and this is wrong. Some Christians use this number to say when God made mankind.  Although most would place Adam within the past 20,000 years.  mtDNA Eve's age is technically the Time to the Most Recent Common Ancestor (TMRCA)   Remember TMRCA cause I will use that acronym a lot.  Mitochondrial Eve isn't the age of our species because mitochondrial are a small part of our DNA. The TMRCA for the vast majority of our genes is much, much older; and each gene has it's own age!

The y chromosome Adam which is the correlate of mitochondrial Eve lived about 338,000 years ago, yet he is not claimed to be the origin time of H. sapiens. Nor should he be.  This age too, is just the TMRCA for this piece of DNA.  But again, small pieces of DNA don't define a species.

So what is the problem? The mtDNA Eve was not the only female on the planet, she was one of a whole lot of females, each of whom had their own mtDNA. But all these other women's lineages died out leaving only descendants of mtDNA Eve. This is no different than the process  whereby family names die off because of a failure to have sons who had offspring.

"In 1790, six mutineers from H.M.S Bounty  arrived on the tiny island, bringing thirteen Tahitian women with them.  Few others have ever gone there to live.  Recently, a population of fifty people on the island shared only four surnames, and one of these was that of a whaler who had later settled on Pitcairn.  Thus in only six or seven generations, 50 percent of the six original surnames had already disappeared.  After a few more generations, only one will remain."1

Barry Starr explains:

"Mitochondrial Eve is simply the last woman we can trace our maternal lines back to.  In other words, she is our mother’s mother’s, etc. all the way back a few hundred thousand years.     "All the other women alive at the time eventually had their maternal lines end.  Either there was a generation with all sons or the daughters had no surviving daughters or whatever.  The descendants of most of these women still walk among us; they are just invisible to the type of testing we can do to look back so far in time.  Again, this all goes for men and Y-Adam too." 2.

 What the mtDNA time represents is the time it took for the descendant copies of this woman's mtDNA to conquer the genetic world of modern humans. It is the TMRCA!  This makes mtDNA time the age of the ancestor for  THIS TINY PIECE OF THE DNA.  It says nothing, about the origin of the  human species, no matter how often this is repeated.  If the only DNA we had in our bodies was mitochondria, then in that case, mtDNA's TMRCA would be the age of our species.  But of course, we have much more DNA than the tiny amount of mitochondria DNA.

Templeton criticizes the hype about mtDNA:

“Because mtDNA is inherited as a maternal haploid, this ancestral mtDNA must have been present in a female. Some scientists and much of the popular media have dubbed this bearer of our ancestral mtDNA “mitochondrial Eve," and have treated this as a startling discovery about human evolution. However, the existence of a mitochondrial Eve is trivial under coalescent theory. Finite population size (and all real populations are finite) ensures that all copies of any homologous piece of DNA present in any species have been derived from a single common ancestral DNA molecule in the past; indeed, this is the very definition of genetic homology. To say that humans have a mitochondrial Eve is to say only that all human mtDNA is homologous. When "Eve" is called the ancestor of us all, it only means that our mtDNA is descended from her mtDNA, and not necessarily any other piece of the human genome.”3

Alan Templeton has a chart that illustrates what happens to make one person the parent of everyone's mitochondria or other piece of DNA.:  

As I noted, the y-chromosome Adam or TMRCA yields at date of 338,000 years. Here is the amazing report,

"We report the discovery of an African American Y chromosome that carries the ancestral state of all SNPs that defined the basal portion of the Y chromosome phylogenetic tree. We sequenced ∼240 kb of this chromosome to identify private, derived mutations on this lineage, which we named A00. We then estimated the time to the most recent common ancestor (TMRCA) for the Y tree as 338 thousand years ago (kya) (95% confidence interval = 237–581 kya)."4

The same kind of math is used on y-chromosome Adam as was used on mtDNA Eve, yet the hullabaloo is only about Eve, because some people are trying to link her with the Out of Africa Replacement theory.  Again, both of these dates are just the age of the last common ancestor OF THAT PIECE OF DNA.  Each piece of DNA has its own age as we shall see in a picture below for a small piece of DNA.

Once we realize this, then the view of what happened in the past changes.  First I need to point out that the mtDNA is haploid and the parts of the y-chromosome they use in y-chromosome Adam's calculation can't cross over (mix with the X chromosome).  This means that when we examine the age of genes in nuclear DNA, the time to the most recent ancestor is quite a lot older than these these two much ballyhooed pieces of DNA, because of crossover. The reason for the hype about the mitochondrial DNA is that it appears to be an attempt to 'prove' the Out of Africa replacement with sleight of hand.

"For example, much of the current debate focuses on whether or not there is an African root, with many participants in this debate still behaving as if the resolution of an African mtDNA root would 'prove' the Out of Africa replacement hypothesis.  As pointed out in the introduction to this chapter and in Templeton(...), only the inference of a non-African root is informative and in this case and all alternatives are consistent with an African mtDNA root.  There is even less potential discriminatory power for nuclear DNA.  Expected coalescence time (that is, the time from the present back to the common ancestral sequence) is a function of the inbreeding effective size for the genetic element under consideration, and this size is innately fourfold larger for nuclear DNA than for mtDNA (because of diploidy vs. haploidy, and bisexual inheritance vs. unisexual inheritance). Moreover, as will be discussed shortly, molecules that do not recombine (such as mtDNA but not  nuclear DNA) show a strong bias towards even shorter coalescence times.  If the coalescence time of mtDNA is truly about 200,000 years ago, then the expected coalescence time of almost all nuclear genes are going to be commonly greater than one or two million years.  This places the expected coalescence times of much nuclear DNA into a period in which all humans probably lived in Africa.  Hence, studies on nuclear DNA are expected to have an African root under all hypotheses of modern human evolution."5

Note he said that molecules that don't recombine (y-chromosome, mtDNA) give anomalously short coalescence times.  Focusing only on these two pieces of DNA misleads us into thinking that our species arose late, about 200,000 years ago, when in fact our genes are much older, 800,000 to 5 million years old.

Using the appropriate mathematics for nuclear DNA to see the age of various alleles does indeed show that much of our genome is over a million years old.  That is, it took over a million years for mutations to create the diversity we see in the  human population.  This is what few want to talk about.  Having everyone focused on a tiny piece of DNA and proclaiming that this tiny piece of mtDNA proves when humanity evolved is indeed silly. What about the rest of the genome? Does it have nothing at all to contribute to the debate? It would be like finding one new species in the ocean and ignoring all other species.

One thing one needs to know is that all the results of genetic estimates come from models and models have assumptions which limit the solutions.  One such set of assumption is, "it the allele evolving in a neutral fashion or being selected for by evolution?"  It makes a difference to the answer. Cagliani, et al note:

"In fact, while neutrally evolving autosomal loci have TMRCAs ranging from 0.8 to 1.5 million years (MY), gene regions under balancing selection may show coalescence times dating back more than 4 MY."6

As Templeton said, the TMRCA majority of nuclear DNA  has a TMRCA of over a million years.  Below is a chart showing the TMRCA of some genes. They chose 27 autosomal genes; the TMRCA is more than 2 million years old in 11 out of 27 of them. Only 2 of the 27 are under a million years in TMRCA. Click on picture to enlarge. 

So we are supposed to ignore these old genes and say that the 16,000 base pairs of  mitochondria outweighs the three billion base pairs of the nuclear DNA and just say nuclear DNA doesn't count?  That is one of the most ridiculous ideas I have seen, yet that is what is happening.  The 16,000 base pairs of the mitochondria  is somehow considered the end all of knowledge about when our species arose. And it represents 0.0000053 or .00053%  of our DNA.  I don't know how many ways I can say it, but we are not a walking piece of mitochondrial DNA. This small piece of our genome (and not even part of our nuclear genome), is NOT what defines our species! Further, other genes have much to say about when they arose, and it differs from mtDNA.

 Below is a chart of the TMRCA for many individual genes. Some is taken from an old web page and others are from my research  this week. Or these are the times it takes for each of these genes to accumulate the mutations we see All of these parts of our DNA are older than mtDNA Eve. These show that our genome was gradually shaped over the past 5 million years.

gene       age of the gene   reference 

Tap2                 5.36 myr        7
ERAP2                5.08 myr        8
green opsin          >5.5 myr     9

HERVs                 5.0 myr        10

TRIM5                 4-7 myr        11

Patr-DRB1*03          4.6 myr        12

DEFB1                 4.5 myr        13

CDSN/PSORS1C1        4.18 myr        7

ERAP1                4.12 myr        8

CD151        3.83 or 2.14 myr        14

CD55         3.19 or 2.61 myr        14

SIGLEC16          3.1-3.8 myr        15

FUT2 coding region    3   myr        14

SLC14A1              2.28 myr        14

Lipoprotein           2.0 myr        9

FUT2 promoter 1.99 or 1.7 myr        14

PDHA1                1.86 myr        16

BSG gene     1.76 or 1.53 myr        14

Beta-globin          1.36 myr        17

dys44                1.35 myr        17

Plp                  1.28 myr        17

Ace                  1.11 myr        17

Pdha1                1.05 myr        17

Melanocortin-1        1.0 myr        18

Zfx                  0,93 myr        17

Lpl                  0.91 myr        17

ß-globin             0.8  myr        18

ms205 minisat.  0.72-1.04 myr        19

Mclr                 0.71 myr        17

non-coding area  X  0.675 myr        20

Xq13.3               0.56 myr        17

Hprt                 0.53 myr        17

Chromosome 22  .504-2.112 myr        21

Gk                   0.41 myr        17

ZDF                 0.306 myr        22

I would like to show a picture from work done by Heng Li and Richard Durbin23 where they took DNA from a Chinese, a Korean, 3 Europeans 2 Yoruba males, and calculated along a strand of DNA how many generations each part of the DNA would take to coalesce to the most recent common ancestor. As you can see, the age varies continuously along the DNA.. The picture is  also fascinating because the spot at 60,000 base pairs takes a little less than200,000 generations.  At 25 years per generation average, we have this region would take a little less than 5 million years for all the observed diversity to arise.  

What does all this mean?  Well, it means we have been one breeding population for 5 or more million years.

Wolpoff wrote:

"There is no distinct boundary between Homo erectus and Homo sapiens in time or space, and cladogenesis does not seem to mark the origin of Homo sapiens.  Instead, the characteristics of Homo erectus and Homo sapiens are found to be mixed in seemingly transitional  samples from the later Middle Pleistocene of every region where there are human remains.  The regional ancestry of Homo sapiens populations makes monophyly impossible for the species if the earlier populations are in a different species.  We interpret this to mean that there is no speciation involved in the emergence of Homo sapiens from Homo erectus. These reasons combine to require that the lineage be regarded as a single evolutionary species."24

The above will surprise many, that a minority anthropologists(but a group of well known ones) think the only speciation event was at the formation of H. erectus; that there was no speciation between erectus and sapiens.

This is not the first time someone tried to push the idea that humans formed one continuous breeding population and only phyletic speciation occurred.  Phyletic speciation is gradual change from one species to another, as Wolpoff above describes, features gradually change, and the fossil record just shows a mixture of traits slowly being more of the new species rather than the old.

From the 1860s until 1950, almost every new fossil find was given a new genus and species name.  It was good for getting newspapers to spread the word about your discovery.  Finding another Pithecanthropus, say, would be placed on page 12 at the bottom.  In 1950 anthropologists held a conference in Cold Springs Harbor, Maine to thrash out the multitudinous names of all the fossil men. They invited Ernst Mayr, a world renown taxonomist to examine the fossils and make suggestion about how to consolidate and make sense of the human fossil record.  Boaz relates the events.

      "The biggest bombshell dropped on the Old Guard, however, came from Ernst Mayr, a German-trained ornithologist and specialist in the naming (taxonomy) of species in nature.  Using the new yardstick of variability within populations, he stated that 'after due  consideration of the many differences between Modern man, Java man, and the South African ape-man, I did not find any morphological characters that would necessitate separating them into several genera.'  He suggested that all the fossil human-like specimens that anthropologists had discovered after so much laborious effort over the preceding century be simply ascribed to one genus, our own--Homo. In other words, the entire 'Age of Description,' from before Darwin to Cold Spring Harbor, was a waste of time.  His opinion was that the differences were not as great as between genera of other animals.  This assertion meant that the wonderfully diverse lexicon of human paleontology, a virtual liguistic playground for the classically educated, with melliferous names such as Plesianthropus transvaalensis, Meganthropus palaeojavanicus, Africanthropus njarensis, Sinanthropus pekinensis, Pithecanthropus erectus, and so on, were to be replaced.  Everything was now to be simply Homo, with three species: Homo transvaalensis, Homo erectus,  and Homo sapiens."       "Mayr's proposal went so far that even Washburn argued that at least the South African Australopithecus be retained (instead of Homo transvaalensis) because it showed such significantly more primitive anatomy than members of the genus Homo. Mayr simply countered that the population is what the species designates.  How one determines a genus is arbitrary.  The definition is gauged by the relative amount  of difference that one sees between the genera of other animals and, in Mayr's opinion, hominid fossils don't show very much difference.  To anthropologists, this statement was a bit like telling a new mother that her baby looks like every other baby.  It did not go over well."25

Below is a quotation of what Mayr said in 1950 at Cold Spring Harbor.

       “Being left with one species of gorilla and one species of chimpanzees, we are confronted by the question whether or not they are sufficiently different to justify placing them in different genera. A specialist of anthropoids impressed by the many differences between these species may want to do so. 0ther zoologists will conclude that the differences between the two species are not indicative of a generic level of difference when measured in the standards customary in most branches of zoology. To place these two anthropoids into two separate genera defeats the function of generic nomenclature and conceals the close relationship of gorilla and chimpanzee  as compared with much more different orang and the gibbons. Recognizing  a separate genus for the gorilla would necessitate raising the orang and the gibbon to subfamily or family rank as has indeed been done or suggested. This only worsens the inequality of the higher categories among the primates. 
           “The same is true for the fossil hominids. After due consideration of the many differences between Modern man, Java man, and the South African ape-man, I did not find any morphological characters that would necessitate separating them into several genera. Not even Australopithecus has unequivocal claims for separation. This form appears to possess what might be considered the principal generic character of Homo, namely, upright posture with its shift to a terrestrial mode of living and the freeing of the anterior extremity for new functions which, in turn, have stimulated brain evolution. Within this type there has been phyletic speciation resulting in Homo sapiens. “26

Yes, indeed, telling anthropologists that their babies look like most other babies, didn't go over well. But, they did take part of Mayr's suggestion and group the erectines in with Homo but left Dart's africanus out in the cold, in another genus.

I emphasized phyletic speciation above. Mayr was saying we have been one breeding population from the pithecines through the erectines and on to the sapiens.   That is exactly  what the TMRCA data is saying. Most of our nuclear genome arose while man was still in Africa, 1.5 Myr ago and a large percentage of our nuclear genome dates back more than 3 million years. So the Out of Africa theory is one of those "Duh! ya think?" ideas.  Of course mankind came out of Africa. It is just that the late, 200,000 years ago Out of Africa theory, when, it is claimed, that our mitochondria walked out of Africa,  isn't all that important. Oh gee, did I say our mitochondria walked out of Africa?  I'm sorry, I meant to say modern man walked out of Africa. Given the hullabaloo about such a small piece of our anatomy, that it is the one thing that defines us as modern humans, you must forgive me for my mistake.

Since we are back to talking about the origin of modern man,  There is no definition in anthropological literature of what is a modern H. sapiens.  No proposed set of traits fully encompass modern men and exclude H. erectus. Wolpoff and Caspari discuss the attempts to define anatomically modern H. sapiens:

    "Modernity is not a 'thing,' a set of features that linked together because they were spread by a single population.  But it's not that modern humans have many sources, rather that modern features  do.  What links modern features together is how they contribute to successful adaptations, and this, with the differing genetic histories of populations from place to place, explains why modernity is not the same everywhere.
     "This is why it has proved impossible to provide an acceptable definition of modernity.  Repeated attempts at a definition based on skeletal variation have failed because when they were applied to skeletal samples, it was found they did not include all recent or living people.  How could this happen?:  It comes back to the importance of Neandertals because these anatomical definitions of modernity cast them in the role of 'other.'  These definitions are based on the assumption Neandertals were not modern humans.  Indeed, they were constructed to exclude Neandertals.  However, when the definitions were applied to populations around the world, it was quickly discovered that significant numbers of Holocene and recently living Aboriginal Indigenous Australians were not 'modern.'  This problem, of course, is not with the Aboriginal Indigenous Australians who are each and every bit as modern as the authors of the definitions, but with the definitions themselves and their focus on Neandertals."27

This just re-enforces the concept that humanity just gradually grew out of being H. erectus, all the while carrying the image of God as shown in the previous post in this blog.  There was no big speciation event for us, just gradual change in this case.  Punctuated equilibria is not a law of physics that must be applied everywhere; it works where it works and fails where it fails.

What about the Major Histocompatibility Complex?

This is supposedly the big bugaboo for anyone who believes in a single pair.  Francis Ayala, years ago, wrote this:

"The coalescence theory of population genetics leads to the conclusion that the DRB1 polymorphism requires that the population ancestral to modern humans has maintained a mean effective size of 100,000 individuals over the 30-million-year persistence of this polymorphism.  We explore the possibility of occasional population bottlenecks and conclude that the ancestral population could not have at any time consisted of fewer than several thousand individuals.  The MHC polymorphisms excluded the theory claiming, on the basis of mitochondrial DNA polymorphisms, that a constriction down to one or few women occurred in Africa, at the transition from archaic to anatomically modern humans, some 200,000 years ago."28

George Murphy noting this difficulty wrote:

"As one example of the difficulty this idea faces, development of the present diversity of alleles of human histocompatibility genes from such a pair would require between five and ten million years.  Unless we want to consider “Adam and Eve” the biological ancestors of all hominids, and perhaps even pongids, we must rule this out."29

If this is true, that there was a big population for 30 million years, then the story of Adam and Eve can't be true, at least not as we currently understand it as a single pair.

It is true that the DRB1 gene has 11,757 alleles in the US population.30  If there were single pair anywhere in the past 200,000 years, the claim is that the human race could not have evolved that much diversity in that time.  After all, Adam and Eve each would have had 2, so at most they could have given their kids 4 of the 11,757 alleles.  But, all is not lost.

Both Ayala and Murphy were using the wrong assumption to model the past. George, who is a friend of mine, didn't look deep enough into the literature. Both he and Ayala are theologically comfortable with a population evolving into Adams and Eves. Thus, like all of us, when we think we have an answer that fits our world view, we cease looking for problems or solutions to problems that might take our world view in different directions.  We all need to guard against that. 

Above, I mentioned how all these results are based upon models, and then the model is treated as metaphysical reality.  Models depend on the assumptions. Change the assumptions and different answers come out. Bergstrom et al, changed the assumptions. Bergstrom et al, argue that almost all of these alleles average around 250,000 years old, solving the vast majority of these problems, if they are right. They pointed out that sequence exchange meant that the alleles didn't evolve mutation by mutation, but the DNA was scrambled by exchanging one base with another base on another allele.  This means the alleles don't make an evolutionary tree, and using the model for an evolutionary tree yields false results.  Bergstrom et al, note,

 "The HLA class I and class II loci are the most highly polymorphic coding regions in the human genome. Based on the similarity of the coding sequences of alleles between species, it has been claimed that the HLA polymorphism is ancient and predates the separation of human (Homo) and chimpanzee (Pan), 4–7.4 Myr ago. Analysis of intron sequences, however, provides support for a more recent origin and for rapid generation of alleles at the HLA class II DRB1 locus. The human DRB1 alleles can be divided into groups (allelic lineages); most of these lineages have diverged from each other before the separation of Homo and Pan. Alleles within such a lineage, however, appear to be, on average, 250,000 years old, implying that the vast majority (greater than 90%) of the more than 135 contemporary human DRB1 alleles have been generated after the separation of Homo and Pan."31

In the article, they point out that these DRB1 alleles, which are so incredibly diverse might not have arisen via mutation but have arisen via sequence exchanges  This has been demonstrated with the mouse.

 "Exchange of sequences between different loci, which has been demonstrated conclusively in mouse class I sequences, most likely involves gene conversion." 32

Bergstrom et al. note,

"Furthermore, the polymorphism at several class II loci, such as DRBI, is characterized by a 'patchwork' pattern of amino-acid motifs, indicating that the alleles may have been generated through sequence exchanges(that is, gene conversion-like events). This implies that adjacent coding sequences may not share the same evolutionary history and are therefore not suited to reconstructing evolutionary relationships among alleles."33

The 2015 article by Rajalingam et al, agrees,

"MHC genes evolve through duplication, followed by diversification, co‐evolution, and sequence exchange." 34

The Bergstrom et al. article is cited for the authors saying that the coalescence time for the introns is 40 Myr, which clearly would rule out a single pair, like Adam and Eve. Below, Ne is the effective population size--originally the number of breeding individuals but defined slightly differently today. They say,

"Assuming that the intron sequences evolve in a neutral manner and with a generation time of 15 years, this coalescence time translates into a long-term (the last 40 Myr) Ne of 700,000 individuals."35

What people don't know, and I want you to understand this, 700,000 individuals is a monstrously large effective population for anything related to hominids in the human line. One also needs to know that the bigger Ne is , the older is the coalescence time (TMRCA).  The following chart will show that. 

The above is an example of what the math produces. One needs to know how much interbreeding there is and what the effective population is, to find TRMCA.  The contour lines on this chart are the times to most recent common ancestor. The horizontal axis is the breeding size, Ne.  As you can see, as Ne gets larger, the time  to TMRCA gets more ancient. The chart above stops at Ne of 24,000. Bergstrom's 40 million year calculation used many times that Ne, 700,000.  One would expect a very ancient TMRCA under that assumption.

But because humans had a genetic bottleneck about 100,000 years ago, giving us an effective population size of about 10,000, Bergstrom et al did an alternative calculation and found. (The first bolding below is again to show you how useless mtDNA coalescence times are for dating our species; the second bolding shows what happens to that 40 myr if the population is reduced to what we think happened)

"...the coalescence time for the haploid and maternally transmitted mtDNA is expected to be one quarter of that for an autosomal locus. The coalescence time for the alleles within DRB1 Allelic lineages based on the intron sequences correspond to about 700,000 years (Ne=10^4 using the intron substitution rate of Li et al and is similar to estimates from other nuclear markers and mtDNA. Thus, when alleles within allelic lineages are compared there appears to be no difference between the effective population size estimates from HLA loci, such as DRB1, and those estimates based on the genetic diversity at other nuclear loci or mitochondrial DNA." 36

Change the assumption of effective population size and voila, instead of 40 million for the TMRCA for the Histocompatibility Complex, we have 700,000 years.  I spent the last 8 years of my career as part of a team making subsurface reservoir models.  I saw over and over that one could get just about what one wanted out of a model if you chose the correct assumptions.  Science by modeling is a risky affair. I saw the same thing with something called synthetic seismograms,which were supposed to show us if the well data matched the seismic.  Appropriate choice of wavelet, could match any well with almost any seismic.  I began to wonder about the usefulness of modeling.

As you can see, the assumptions are crucial to the answer. But it is clear that the Major Histocompantibility Complex might not be as hard a problem as has been claimed.  The problem is that when one believes that there is no Adam and Eve, as Ayala did, (he wrote a paper, The Myth of Eve), then he won't challenge his assumptions to see if alternatives would work. This is a human nature problem we all have to worry about.

Conclusion

It is clear from genetics, that if there is to be an Adam and Eve, a single pair, as the Bible describes, they must have lived before 5 million years ago. It is for this reason that the previous post on small brained hominids is so crucial.  One of them was our ancestor  It is also clear that the DRB1 location might not eliminate the  idea of a single pair as is often claimed.

Next I will explain some of the implications of these TMRCA's to the paleontological record.When Did Adam Live pt 4 Curse of the Big Head

References

1.  James R. Shreeve, The Neandertal Enigma, (New York: William Morrow and Co., 1995), p. 772.Barry Starr, "Ancestry," https://genetics.thetech.org/ask-a-geneticist/y-adam-and-mitochondrial-eve3. Alan R. Templeton, “Haplotype Trees and Modern Human Origins,” Yearbook of Physical Anthropology, 48(2005):33-59, p.344. Fernando Mendez, et al, An African American Paternal Lineage Adds an Extremely Ancient Root to the Human Y Chromosome Phylogenetic Tree American Journal of Human Genetics, March 2013, p. 454-459, p. 454.5. Alan R. Templeton, "Testing the Out of Africa Replacement Hypothesis with Mitochondrial DNA Data," in G. A. Clark and C. M. Willermet, ed., Conceptual Issues in Modern Human Origins Research, (New York: Aldine de Gryuter, 1997), pp. 329-360, p. 3536.Rachele Cagliani  et al, "Balancing selection is common in the extended MHC region but most alleles with opposite risk profile for autoimmune diseases are neutrally evolving," BMC Evolutionary Biology201111:171, p. 87. Rachele Cagliani  et al, "Balancing selection is common in the extended MHC region but most alleles with opposite risk profile for autoimmune diseases are neutrally evolving," BMC Evolutionary Biology201111:171,  p.8-10http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.937.2885&rep=rep1&type=pdf8. Rachele Cagliani, et al,  2010a "Genetic diversity at endoplasmic reticulum aminopeptidases is maintained by balancing sslection and is associated with natural resistance to HIV-1 invection."  HMG Advance Access published September 15, 2010, http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.937.2885&rep=rep1&type=pdf  p. 99. Ayala, Francisco J., Ananias Escalante, Colm O'hUigin, and Jan Klein, "Molecular Genetics of Speciation and Human Origins," Proc. Natl. Acad. Sciences, USA, Vo. 91:6787-679410. Johnson, Welkin E. and Jon M. Coffin, 1999 "Constructing Primate Phylogenies from Ancient Retrovirus Sequences," Proc. Natl. Acad. Sci., USA, 96:10254-1026011. R. Cagliani et al, 2010b " Long-term balancing selection maintains trans-specific polymorphisms in the human TRIM5 gene,  Human Genetics, 2010, p. 557-588, p. 577.12. Yasukochi and Satta, Journal of Physiological Anthropology 2014, 33:14 Page 3 http://www.jphysiolanthropol.com/content/33/1/14https://jphysiolanthropol.biomedcentral.com/articles/10.1186/1880-6805-33-1413. Rachele Cagliani, et al, 2008, " The signature of long-standing balancing selection at the human defensin β-1 promoter," Genome Biology20089:R143, p R143.1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592704/14  Matteo Fumigalli, et al, Widespread balancing selection and pathogen-driven selection at blood group antigen genes Genome Res. 2009 Feb; 19(2): 199–212. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652214/15. Xiaoxia Wang et al, " Evolution of Siglec-11 and Siglec-16 Genes in Hominins," Molecular Biology and Evolution, Volume 29, Issue 8, August 2012, Pages 2073–2086 https://academic.oup.com/mbe/article/29/8/2073/104478416. Harris, Eugene and Jody Hey, "X Chromosome Evidence for Ancient Human Histories" Proceedings Nat'l Academy of Sciences, U.S.A. 96:3320-332417. Takahata et al, "Testing Multiregionality of Modern Human Origins," Mol. Biol. Evol., 18(2001):2:172-18318. Harding, Rosalind M. et al, 1997, "Archaic African and Asian Lineages in the Genetic Ancestry of Modern Humans," Am. Journal of Human Genetics, 60:772-78919. Alonso, Santos and John A. L. Armour, 2001, “A Highly Variable Segment of Human Subterminal 16p Reveals a History of Population Growth for Modern Humans Outside Africa,” Proc. Natl. Acad. Sci., USA, 98:3:864-869, p. 86820. Kaesmann, H., V. Wiebe and S. Paabo, 1999, "Extensive Nuclear DNA sequence Diversity Among Chimpanzees,  Science 286:1159-1162 cited by John Relethford, 2001, Genetics and the Search for Modern Human Origins, (New York: John Wiley).21.  Zhao, Zhongming et al, “Worldwide DNA sequence variation in a 10-kilobase noncoding region on human chromosome 22” Proc. Natl. Acad. Sci. USA, Vol. 97, Issue 21, 11354-11358, October 10, 200022. Huang, W., Fu Y-X, Chang BHG, Gu X, Jorde L.B. and Li W-H, 1998, "Sequence Variation in ZFX Introns in Human Populations," Molecular BIology and Evolution 15:138-142 cited in John Relethford, 2001, Genetics and the Search for Modern Human Origins, (New York: John Wiley).23. Heng Li and Richard Durbin Inference of Human Population History From Whole Genome Sequence of A Single Individual Nature. 2011 Jul 13; 475(7357): 493–496. https://europepmc.org/articles/pmc315464524. Milford H. Wolpoff, Alan G. Thorne, Jan Jelinek, Zhang Yinyun, "The Case for Sinking Homo erectus. 100 Years of Pithecanthropus is Enough!" Courier Forshungs_Institute Senckenberg 171:341_361, Frankfurt am Main 1.05.1994, p. 34125. Noel Boaz, Quarry, (New York: The Free Press, 1993), p. 1026. Ernst Mayr, “Taxonomic Categories in Fossil Hominids,” Cold Spring  Harbor Symposia on Quantitative Biology, 15(1951)pp109-117,reprinted  in William White Howells, Ideas on Human Evolution, (Cambridge: Harvard University Press, 1962), pp 241-256, p. 24527. Milford Wolpoff and Rachael Caspari, Race and Human Evolution, (New York: Simon and Schuster, 1997), p. 31328. Francisco J. Ayala, Ananias Escalante, Colm O'huigin and Jan Klein, "Molecular Genetics of Speciation and Human Origins," Proc. Natl. Acad. Sci, USA, 91:pp6787-6794, July 1994, p. 6787.29. George L Murphy, Roads to Paradise and Perdition: Christ, Evolution, and Original Sin, Perspectives on Science and Christian Faith, June 2006, p. 11430. https://bioinformatics.bethematchclinical.org/templates/displaypagecontent/?id=937631. Bergström T F, Josefsson A, Erlich H A and Gyllensten U (1998) Recent origin of HLADRB1 alleles and implications for human evolution, Nat Genet. 18 (3):237–242., p. 23732. John Trowsdale ."The gentle art of gene arrangement: the meaning of gene clusters," Genome Biology, 2002, Volume 3, Number 3, https://genomebiology.biomedcentral.com/articles/10.1186/gb-2002-3-3-comment2002
33.Tomas Bergstrom, et al, "Recent Origin of HLA-DRB1 alleles and Implications for Human Evolution," Nature Genetics, 1998, p. 237 https://genomebiology.biomedcentral.com/articles/10.1186/gb-2002-3-3-comment200234. Raja Rajalingam, et al, Transplant Immunology " Major histocompatibility complex" in Xian Chang Li Anthony M. Jevnikar editors, Transplant Immunology, Wiley, 2015, https://onlinelibrary.wiley.com/doi/10.1002/9781119072997.ch535.Tomas Bergstrom, et al, "Recent Origin of HLA-DRB1 alleles and Implications for Human Evolution," Nature Genetics, 1998, p. 24136.Tomas Bergstrom, et al, "Recent Origin of HLA-DRB1 alleles and Implications for Human Evolution," Nature Genetics, 1998, p. 241