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Adam and the Genome and Human Genetic Diversity

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genetic diversity

As we’ve found, much of what BioLogos writer Dennis Venema says in his new book, Adam and the Genome, is not directly relevant to his ostensible topic. What may be Venema’s strongest attempt at making an on-point argument comes in his discussion of human genetic diversity. According to Venema, a biologist at Trinity Western University in British Columbia, this diversity is so great that it demands we arose from a large ancestral population, probably of about 10,000 individuals, and not some initial couple. As we’ll see here and in a following post, the jury is still out on Venema’s claim.

As he puts it:

Taking into account the human mutation rate, and the mathematical probability of new mutations spreading in a population or being lost, these methods indicate an ancestral population size for humans right around that 10,000 figure. In fact, to generate the number of alleles we see in the present day from a starting point of just two individuals, one would have to postulate mutation rates far in excess of what we observe for any animal. (p. 48)

We should note here that this argument has no bearing upon the merits of intelligent design. ID is not dependent upon any theological or scientific viewpoint related to Adam and Eve. In fact, ID is not incompatible with human-ape common ancestry, even though many arguments for such ancestry aren’t nearly as strong as they’re held out to be. We’ve seen as much already in this series.

Does Venema’s Confidence Hold Up?

That having been said, Dr. Venema seems very confident that a traditional Adam and Eve are refuted by the data. Indeed, he asserts that his conclusion is as scientifically strong as the heliocentric model of the solar system. In his words:

The sun is at the center of our solar system, humans evolved, and we evolved as a population.

Put most simply, DNA evidence indicates that humans descend from a large population because we, as a species, are so genetically diverse in the present day that a large ancestral population is needed to transmit that diversity to us. To date, every genetic analysis estimating ancestral population sizes has agreed that we descend from a population of thousands, not a single ancestral couple. (p. 55)

So, by implication, if you doubt Dennis Venema’s point about Adam and Eve, you’re about as ignorant and backwards as a geocentrist.

This is some pretty extreme rhetoric. Venema has been called out on it by biologist Richard Buggs, who observed:

Venema declares that a bottleneck of two is impossible, and this is a fact of comparable scientific certainty to heliocentrism. He gives his Christian readers a stark choice between embracing mainstream science, or sticking with untenable beliefs about an ancestral couple.

This is fine, so long as mainstream science really is showing that a single-pair bottleneck somewhere in the history of humankind is an absolute impossibility. But having looked at the evidence that Venema describes and cites, I am not yet convinced. I can’t echo him and say to someone who believes in an extreme human population bottleneck that they are against science. I will explain my reasoning, taking each of the lines of evidence that he cites in turn.

Undeterred, Venema continues to push his comparison with heliocentrism. We’ll discuss this ongoing exchange between Buggs and Venema below. For now, it suffices to say that Buggs reviewed much of the literature cited by Venema about human ancestral population sizes, and noted, “I am sure the authors of the study would not view their results as being of equivalent certainty to heliocentrism.”

Venema has tried to temper his claims a little, now saying that his “scientific confidence” on the question is not quite absolute. He writes: “I also don’t think that science has ‘disproven’ geocentrism — the idea that the earth is the immobile center of the universe” since science is a “powerful, yet limited, way of knowing” where “everything in science is held, at least in some sense, tentatively.”

Those are reasonable statements, often heard, about the nature of scientific inquiry. One might even call them truisms. But have they really diminished the hyper-confidence of the claim he’s making? No, not really. Venema’s certainty that a traditional Adam and Eve are refuted is still extremely high — about as high as any scientific claim can be. 

But in Adam and the Genome, Venema goes even further. He asserts that there is “no one” in the ID movement capable of properly evaluating the data on Adam and Eve. Venema writes:

[T]here does not appear to be anyone in the antievolutionary camp at present with the necessary training to properly understand the evidence, much less offer a compelling case against it. (p. 65)

Nobody in the ID community is capable of showing him to be wrong? Well, that’s a bit heavy on the attitude. It’s not the only insult in the book directed our way, either.

An Email from Richard Buggs

One person who is quite capable of evaluating the evidence is Richard Buggs, an Oxford University-trained evolutionary genomicist at Queen Mary University of London, who has published in this field. Buggs took an interest in Venema’s arguments and has written some courteous, well-informed, and compelling — if somewhat technical — critiques.

Back in May 2017, Buggs sent a personal email to Dr. Venema explaining that under the rules of population genetics, it is possible to have great genetic diversity in a short period of time, even when starting from a founding population of two individuals. Months went by without an answer from Venema, so Buggs made his email public. In the letter, Buggs wrote:

I was a bit surprised that you categorically state in your book that the past human effective population size has definitely never dropped below 10,000 individuals and say that this is a fact of comparable scientific certainty to heliocentrism. Most people working in the field take reconstructions of effective population size with a pinch of salt. I well remember my surprise as a newly graduated PhD student attending a summer school on molecular evolution at Edinburgh University in 2005 on hearing Gil McVean from Oxford say over breakfast that effective population size is a nebulous concept. As I am sure you know, effective population size is a measure of a population’s susceptibility to drift, rather than an attempt to measure census population size. I would be very hesitant to rely too heavily on any estimate of past effective population size.

To get more specific, I think you are mistaken when you say this:

“If a species were formed through such an event [by a single ancestral breeding pair] or if a species were reduced in numbers to a single breeding pair at some point in its history, it would leave a telltale mark on its genome that would persist for hundreds of thousands of years — a severe reduction in genetic variability for the species as a whole”

It is easy to have misleading intuitions about the population genetic effects of a short, sudden bottleneck. For example, Ernst Mayr suggested that many species had passed through extreme bottlenecks in founder events. He argued that extreme loss of diversity in such events would promote evolutionary change. His intuition about loss of diversity in bottlenecks was wrong, though, and his argument lost much of its force when population geneticists (M. Nei, T. Maruyama and R. Chakraborty 1975 Evolution, 29(1):1-10) showed that even a bottleneck of a single pair would not lead to massive decreases in genetic diversity, if followed by rapid population growth. When two individuals are taken at random from an existing large population, they will on average carry 75% of its heterozygosity (M. Slatkin and L. Excoffier 2012 Genetics 191:171–181). From a bottleneck of a single fertilised female, if population size doubles every generation, after many generations the population will have over half of the heterozygosity of the population before the bottleneck (Barton and Charlesworth 1984, Ann. Rev. Ecol. Syst. 15:133-64). If population growth is faster than this, the proportion of heterozygosity maintained will be higher.

This means that a single pair of individuals can carry a great deal of heterozygosity with them through a bottleneck, if they come from an ancestral population with high diversity, and they will pass that on to the population they found, so long as it grows rapidly.

As you will know, it is a feature of humans that despite our current census population size of over seven billion individuals, we have lower genetic diversity than the world’s much smaller current day population of chimpanzees. The average human has 3.1 million single nucleotide variants (SNVs), but the average chimp has 5.7 million (Prado-Martinez et al 2013 Nature). African humans approximately 1.1 heterozygous SNVs in every 1000bp, whereas central chimpanzees have approximately 1.75 (Prado-Martinez et al 2013 Nature). Thus, if two central African chimpanzees were taken today and used to found an isolated population that experienced explosive population growth, the new population would have similar levels of genetic variability to modern humans.

I am not stating these figures because existing populations of chimpanzee gave rise to modern humans, but simply to show that it is hard to see how overall levels of SNP diversity and heterozygosity in modern humans could exclude the possibility of a past bottleneck of two individuals.

On top of this, we need to add in the fact that explosive population growth in humans has allowed many new mutations to rapidly accumulate in human populations, accounting for many SNPs with low minor allele frequencies (A. Keinan and A. G. Clark (2012) Science 336 (6082): 740-743).

I am also concerned about your interpretation of PSMC [Pairwise Sequentially Markovian Coalescent] analysis. I do not think that a PSMC analysis that never drops below an Ne of 10,000 can be used to prove that a sudden, short bottleneck never happened. Because a single couple can carry with them 0.75 of the heterozygosity of their ancestral population, we would not expect a huge number of coalescence events at the bottleneck, and those that are there were would be smeared out over a long period of time around the bottleneck, as within the orginal Li and Durbin 2011 paper, the authors note:

“The simulations did, however, reveal a limitation of PSMC in recovering sudden changes in effective population size. For example, the instantaneous reduction from 12,000 to 1,200 at 100 kyr ago in the simulation was spread over several preceding tens of thousands of years in the PSMC reconstruction.” (Li and Durbin 2011).

Work by a graduate student in Beth Shapiro’s lab has shown that the PSMC method cannot accurately reconstruct sharp bottlenecks….

In general, I am concerned that the studies you cite did not set out to test the hypothesis that humans have passed through a single-couple bottleneck. They are simply trying to reconstruct the most probable past effective population sizes of humans given the standard assumptions of population genetic models. I personally would feel ill at ease claiming that they prove that a short sudden bottleneck is impossible.

In other words, according to Buggs, the papers cited by Venema don’t make his case. They don’t actually refute the hypothesis that humanity passed through a bottleneck of two individuals with great genetic diversity. If Buggs is correct, then Venema’s primary argument against Adam and Eve is insufficient.

This debate between Buggs and Venema is ongoing — but proceeding slowly. It took Venema some six months to reply to Buggs, and when Venema did respond, he noted that heterozygosity (the percentage of the population that has two different alleles at a given locus) is not the only basis for his claim of a large (much greater than two initial individuals) ancestral human population. Rather, Venema explained that he also argues against Adam and Eve on the basis of allelic diversity — the number of different alleles present in a population at a given locus:

The key here is that one individual can only have at most two alleles of any gene. A population reduction to one breeding pair would mean that at most, four alleles of a given gene could pass through the bottleneck — in the case where both individuals are heterozygous, and heterozygous for different alleles. The population would then have to wait for new mutation events to produce new alleles of this gene — a process that will take a significant amount of time. Since this would happen to all genes in the genome at the same time — a reduction to a maximum of four alleles — we would notice this effect for a long time thereafter as genetic diversity was slowly rebuilt across the genome as a whole.

So, a bottleneck to two individuals would leave an enduring mark on our genomes – and one part of that mark would be a severe reduction in the number of alleles we have — down to a maximum of four alleles at any given gene. Humans, however, have a large number of alleles for many genes — famously, there are hundreds of alleles for some genes involved in immune system function. These alleles take time to generate, because the mutation rate in humans is very low. This high allele diversity is thus the first indication that we did not pass through a severe population bottleneck, but rather a relatively mild one (estimated, as we have discussed, at about 10,000 individuals by current methods).

Venema also charged that Buggs was wrong to focus on the argument from heterozygosity since, he says, “This is not the same thing…as retaining a significant proportion of the population’s genetic diversity.” High degrees of heterozygosity, Venema acknowledges, can survive a bottleneck, whereas high allelic diversity cannot.  Thus, Venema concludes that our high allelic diversity refutes the idea that the human species went through a bottleneck of two individuals.

Buggs also wrote an initial response to Venema at his Nature Ecology and Evolution blog. He noted there that in Adam and the Genome, Venema focused on Tasmanian devils, which are known for their very low levels of heterozygosity, suggesting heterozygosity was important to his overall argument. In any case, Buggs then replied to Venema’s response at his personal blog. He pointed out that his focus on heterozygosity was reasonable, since Venema had written about Tasmanian devils:

The majority of your blog is taken up with the topic of genetic diversity. I think that we are largely in agreement here. I am glad that you agree with the points I made about the amount of heterozygosity that can be carried through a short, sharp bottleneck. I do not dispute that allelic diversity can provide stronger evidence for a past bottleneck than heterozygosity can. In my blog I stated this clearly: “A sharp bottleneck will affect allelic richness more than heterozygosity”. I am grateful that you have helped out non-scientists who are seeking to follow our debate by giving a simple “Genetics 101” explanation of why this is so in your blog.

Although we are in agreement about the relative merits of heterozygosity and allelic diversity in detecting bottlenecks, misunderstanding between us has arisen for two reasons: (1) ambiguous usage of the term “genetic variability” in your book chapter, and (2) the choice of Tasmanian Devils in your book chapter as an example of the consequences of a population bottleneck.

Buggs observes that a major barrier to clarity in this conversation has been Venema’s use of the terms “genetic diversity” or “genetic variability.” He uses them in an ambiguous manner, different from how the terms are often used in the scientific literature. As Buggs explains:

(1) I commented on heterozygosity in my email and blog because in your book chapter you refer many times to “genetic variability”. As you know, in scientific population genetics literature the term “genetic variability” does not refer only to allelic diversity. Genetic variability of populations is measured in many ways: heterozygosity, allelic diversity, private allele frequency, gene diversity, fixation indices, inbreeding coefficients etc. I did not realise that when you use the term in your chapter you intend only to refer to allelic diversity. That is not the way the term is normally used in the field. I therefore assumed that you were also referring to heterozygosity. It is a pity that this ambiguity was present, but I understand that it is hard to write about science at a popular level without the occasional ambiguity slipping in that a specialist will stumble on.

(2) I also got the impression you are including heterozygosity within your definition of genetic variability because of your choice of Tasmanian Devils as an exemplar of a species that has undergone a bottleneck. This exemplar takes up quite a large proportion of the early part of your chapter. It is well known that Tasmanian devils have low heterozygosity as well as low allelic diversity — they have much lower levels of heterozygosity than humans…

Up to this point, Buggs and Venema seem to agree on two things: (1) High levels of heterozygosity can survive a bottleneck (meaning they probably could not refute Adam and Eve), and (2) high levels of allele diversity typically cannot survive a bottleneck (meaning they potentially could form an argument against Adam and Eve). But this story is far from over. As Buggs explained in his Nature Ecology and Evolution post, there are ways to rapidly generate high allelic diversity even after a very short, sharp bottleneck:

A maximum of four alleles can pass through a bottleneck of two individuals. At the level of single nucleotide polymorphisms (SNPs) this is not such an issue as the maximum number of alleles possible at a SNP is four (A, T, G or C), and most common human SNPs are biallelic anyway (1000 genomes project). When we consider a contiguous sequence of DNA, such as a haplotype of a gene, more than four alleles are common, but these can arise through recombination of ancestral SNPs (in which case we have to ask if patterns of linkage disequilibrium fit with a bottleneck – upon which more below) or through new mutations. We need to bear in mind that explosive population growth in humans has allowed many new mutations to rapidly accumulate in human populations (A. Keinan and A. G. Clark (2012) Science 336: 740-743). [Emphasis added.]

The text in bold above could potentially pose a serious challenge to Venema’s claims that large allelic diversity necessarily precludes an ancestral couple. Why? Because it suggests that high allelic diversity could potentially arise even from a short, sharp bottleneck. But Venema did not respond (not as of this writing, at least) to this particular argument. Instead, Venema replies as if Buggs’s main arguments were about heterozygosity, and thus seems to be distracting from these good points on allelic diversity.

Buggs: Other Arguments from Venema Also Don’t Refute Adam and Eve

In Adam and the Genome, Venema makes other arguments for a large human ancestral population based upon patterns of linkage disequilibrium, the pairwise sequentially Markovian coalescent (PSMC) model, and incomplete lineage sorting (ILS). In his Nature Eco-Evo post, Buggs explains why each of these arguments fails to establish a large ancestral population size. As we write this, Venema has not responded to those comments either.

Regarding Venema’s arguments from linkage disequilibrium, Buggs says:

Obviously, however, the paper at no point gives an effective population size estimate as low as two individuals. Does this therefore disprove the hypothesis of a bottleneck of two? I don’t think so, because such a scenario is simply not on the radar of the methods employed. The methods assume that the populations at any given time point are at equilibrium and not expanding exponentially (the authors deliberately exclude the last 10,000 years from this analysis as they know that exponential population growth has occurred in this timeframe). It is hard to see how they could pick up on a short, sharp bottleneck even if one had happened. It would be nice to see this modelled, just to check.

Even if the results of this study are entirely correct, the authors do not make any statements about population size more than 200,000 years ago. This would appear to leave open the possibility of a bottleneck in the previous 5.8 million years.

Regarding Venema’s arguments from the pairwise sequentially Markovian coalescent (PSMC) model, Buggs writes:

Does this prove that a sudden, short bottleneck never happened? I don’t think so. Because a single couple can carry with them 0.75 of the heterozygosity of their ancestral population, we would not expect an extreme number of coalescence events at the bottleneck. Furthermore, those that are there were would be smeared out over a long period of time around the bottleneck. … More recently, some simulations by a graduate student have shown that the PSMC method does not detect short, sharp bottlenecks, such as those caused by a pandemic or natural disaster. Thus I cannot see that PSMC analyses (many more of which have been done on human genomes since the original paper by Li and Durbin) can be cited as rigorously disproving a short, sharp bottleneck.

Regarding Venema’s arguments from incomplete lineage sorting (ILS), Buggs writes:

Venema makes an argument based on incomplete lineage sorting among humans, apes and gorillas, which gives a large estimated effective population size. This argument is not relevant if we are only interested in the human lineage (the occurrence of ILS does not require maintenance of large populations sizes in every lineage after speciation and so does not exclude a bottleneck in the exclusively human lineage).

So Richard Buggs has now responded to five classes of arguments that Dennis Venema makes in Adam and the Genome: on (1) heterozygosity, (2) allele diversity, (3) linkage disequilibrium, (4) the pairwise sequentially Markovian coalescent (PSMC) model, and (5) incomplete lineage sorting. Where, then, do we stand?

Regarding (1), Venema has agreed with Buggs that this type of argument does not necessarily refute Adam and Eve. Regarding (3), (4), and (5), Venema has not yet responded to Buggs. Regarding (2), Venema has argued that a short bottleneck would greatly reduce allelic diversity, and Buggs has generally agreed with him on. However, Venema has not responded to the point from Buggs that “explosive population growth in humans” could rapidly generate high allelic diversity even after a short, sharp bottleneck.

We won’t assume that Venema has nothing more to say in reply to Buggs. But so far, Buggs’s courteous and professional exhortation to Venema in his original email still seems appropriate: “I would encourage you to step back a bit from the strong claims you are making that a two-person bottleneck is disproven.”

At present, the conversation is focused on whether allelic diversity can or does show that humans never went through a very small bottleneck of two individuals. Can modeling demonstrate that explosive human population growth could produce the high levels of observed human allelic diversity? Venema says the question is closed, but Buggs thinks it  remains open, strongly meriting further investigation.

Another crucial question remains: Has any scientific study yet shown that human allelic diversity requires an ancestral population of thousands of individuals rather than just two? From Adam and the Genome, you get the stong impression that the answer is yes. But from Venema’s admissions when pressed by Buggs for a citation to back up his claims, you come away with the equally distinct impression that the answer is no. We’ll have more to say on that, coming up.

Photo credit: geralt, via Pixabay.