Dennis Venema is a biologist and prominent theistic evolutionist associated with the group BioLogos. Yesterday, Douglas Axe responded to Venema’s critical review of Axe’s book Undeniable, pointing to what you might call citation bluffing. We, meanwhile, have been taking an extended look at Venema’s own book, Adam and the Genome, and his defense of it. These are marred by the same problem.

Earlier, we saw that evolutionary genomicist Richard Buggs has been engaged in a dialogue with Venema about the latter’s arguments against a short bottleneck of two individuals in human history. Buggs is skeptical that methods of measuring human genetic diversity cited by Venema can adequately test such an “Adam and Eve” hypothesis. Buggs’s initial email to Venema thus concluded, “I would encourage you to step back a bit from the strong claims you are making that a two person bottleneck is disproven.”

Buggs agreed with Venema that one particular metric — human allelic diversity — might be capable of testing the issue. But he wanted to know more details about the population genetics models that Venema was relying on. In reply to Venema’s response to his initial email, Buggs asked Venema to provide a citation. He requested some backup for the repeated claims that human allelic diversity indicates we evolved from an ancestral population of about 10,000 individuals.

Ultimately Dr. Venema was unable to provide a scientific citation to substantiate his claim. To be fair to Venema, he says he believes that he has provided an adequate citation. And no doubt he sincerely does believe it. There is no accusation of bad faith here. But Buggs has clearly shown that Venema did not provide adequate backup. This means that Venema’s claims against Adam and Eve are scientifically suspect and intellectually unpersuasive. In fact, Buggs has shown that some of Venema’s citations don’t even address the question of the ancestral population size of humans. This gives the appearance of “citation bluffing,” however unwitting.

The exchange casts further doubt on claims that Venema and BioLogos have been making for years about Adam and Eve. To see why, we’re going to have to review some of the highlights of the dialogue between Venema and Buggs.

Highlights of a Dialogue

We start with a comment from Buggs in reply to Venema’s response to Buggs’s initial email. (Are you following this so far?) Buggs had reviewed Venema’s arguments in Adam and the Genome and respectfully requested a citation. Here’s what Buggs wrote:

One of your most explicit statements about this in your book chapter is as follows:

“[Quoting Venema in Adam and the Genome:] …scientists have many other methods at their disposal to measure just how large our population has been over time. One simple way is to select a few genes and measure how many alleles of that gene are present in present-day humans. Now that the Human Genome Project has been completed and we have sequenced the DNA of thousands of humans, this sort of study can be done simply using a computer. 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.”

As I note in my blog, you give no citation to the scientific literature to back up this point, so it is hard for me to interact with you on it. I would invite you again to make such a citation so that we can discuss this point further.

In your recent blog you have now made a similar claim, and given more detail:

“[Quoting Venema’s blog response:] 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).”

Would I be correct in assuming that this statement in your blog is intended to illuminate the passage I quoted above from your book chapter? If so, this is helpful as you give a link in the blog to an online primer about Human leukocyte antigen (HLA) genes, suggesting that your argument relates to these genes. But the online primer has nothing in it about models of past human bottlenecks. I would invite you to make a more explicit argument on this point, as I think this is the strongest argument that is available to you against a bottleneck of two. As you mention HLA genes in your blog, it sounds to me as if your argument may rest on Ayala et al (1994) but this paper was published before the human genome project, so I assume you must have a more up to date source that you drew on for your book chapter. Please could you let me know what it is so that I can follow up your argument? [Emphasis added.]

So did Venema provide a citation to back up his claims? No, definitely not in the manner that Buggs requested. Instead, Venema writes in response: “Some of the citations you‘re looking for are just working familiarity with published data sets.” This vague answer to Buggs provoked his curiosity, and his concern. Buggs responds again with politeness, clarity, and specificity:

I think I must check at once that I am not misunderstanding or reading too much into your statement here. Do I understand you to be saying is that you will not be giving me citations to the peer-reviewed literature to back up certain of the claims in Adam and the Genome that I am querying? If so, I have to reassess somewhat my expectations for our discussion.

Venema then denied that he was not providing specific citations:

No, I‘m not saying that. I am saying this is my understanding of the published literature and the relevant publically-available databases. Li and Durban would be one paper relevant here; moreover the 1,000 genomes consortium papers, papers that estimate the present-day human mutation rate, and so on.

Venema also linked to a 2015 Nature paper on the 1000 Genomes Project, which had endeavored to sequence the genomes of at least 1000 anonymous humans from diverse racial and ethnic groups around the world.

This response from Venema at least pointed to scientific papers. However, Buggs then notes that the papers Venema cited do not in fact establish that humans did not go through a short, sharp bottleneck of two individuals. Buggs writes, “[A]s far as I can see, the 1,000 Genomes paper does not do the calculations that you report in that passage. Unless I am missing something, the authors do not report a calculation of ancestral population sizes from the number of alleles found in present day populations.” This response from Buggs is worth reading in full:

Thank you for such a quick response to my query, and thank you for the citation to Li and Durbin and to the 1000 genomes project.

“[Quoting Venema’s blog comment:] I am saying this is my understanding of the published literature and the relevant publically-available databases.”

I had assumed that was the case as this is what one expects from a scientist. This is of course, why, as a fellow scientist, I am asking you — I hope courteously and professionally — to point me to the exact papers in the published literature, and to actual analyses of the public databases that support the claims you are making in Adam and the Genome.

“[Quoting Venema’s blog comment:] Li and Durban would be one paper relevant here

Thank you. As you know, this is the paper that presents the PSMC method. In my email to you and my blog I have explained why I do not think that the PSMC method is able to detect a short sharp population bottleneck. I assume that you are going to respond to my comments on PSMC in Part II of your response, so I will not press you further on this issue now.

“[Quoting Venema’s blog comment:] moreover the 1,000 genomes consortium papers, papers that estimate the present-day human mutation rate, and so on. For example A global reference for human genetic variation”

I can see how the 1,000 genomes project can provide the raw data for an analysis such as the one I am asking you for clarification on — the one that you mention in the passage from your book that I quoted in my previous post (above).

However, as far as I can see, the 1,000 genomes paper does not do the calculations that you report in that passage. Unless I am missing something, the authors do not report a calculation of ancestral population sizes from the number of alleles found in present day populations. They do present several PSMC analyses (which are based on runs of heterozygosity within genomes) but they do not seem to present the calculation that you mention in the passage I quoted from Adam and the Genome. Is there another paper in which they conduct the calculations that you are telling your readers about? As I say, I am very keen to know what genes were used in these calculations and how they generated an ancestral population size of 10,000.

Buggs’s writing is very clear, and again at the end, he has requested a specific citation analyzing the diversity of specific alleles and coming to a conclusion that the human ancestral population size was ~10,000 individuals.

The Field as a Whole

Can Venema provide it? Apparently not. Instead, Venema ambiguously cites “the field as a whole”:

What I‘m talking about there is a summary of the field as a whole — and the PSMC analyses in the 1,000 genomes paper is certainly one of the relevant experiments. So are LD studies. So are the Li and Durban PSMC results.

If vaguely citing “the field as a whole” or a “working familiarity with published data sets” is the best Venema has to offer, then Buggs isn’t buying it. Buggs explains why Venema’s response is not sufficient:

Regarding the passage from chapter 3 of Adam and the Genome that I am asking you for citations to support. You have responded in your comment above:

“[Quoting Venema’s blog comment:] What I‘m talking about there is a summary of the field as a whole — and the PSMC analyses in the 1,000 genomes paper is certainly one of the relevant experiments. So are LD studies. So are the Li and Durban PSMC results.”

I am sorry, I am struggling to follow you here. I‘m afraid I can‘t see how that passage is a summary of the field as a whole, and therefore I don‘t understand how citations of the PSMC and LD studies support it.

Here is the passage that we are discussing in its context in Adam and the Genome: I have placed it in italics, and also added some emphases in bold.

“[Quoting Venema in Adam and the Genome:] …given the importance of this question for many Christians — and the strong insistence of many apologists that the science is completely wrong — it is worth at least sketching out a few of the methods geneticists use that support the conclusion that we descend from a population that has never dipped below about 10,000 individuals. While the story of the beleaguered Tasmanian devil provides a nice way to ‘see‘ the sort of thing we would expect if in fact the human race began with just two individuals, scientists have many other methods at their disposal to measure just how large our population has been over time. One simple way is to select a few genes and measure how many alleles of that gene are present in present-day humans. Now that the Human Genome Project has been completed and we have sequenced the DNA of thousands of humans, this sort of study can be done simply using a computer. 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. Ah, you might say, these studies require an estimate of mutation frequencies from the distant past. What if the mutation frequency once was much higher than it is now? Couldn’t that explain the data we see now and still preserve an original founding couple? Aside from the problems this sort of mutation rate would present to any species, we have other ways of measuring ancestral population sizes that do not depend on mutation frequency. These methods thus provide an independent way to check our results using allele diversity alone. Let’s tackle one of these methods next: estimating ancestral population sizes using something known as ‘linkage disequilibrium.’”

Then, after describing the LD study you write:

“[Quoting Venema in Adam and the Genome:] The results indicate that we come from an ancestral population of about 10,000 individuals — the same result we obtained when using allele diversity alone.”

A little later you write

“[Quoting Venema in Adam and the Genome:] A more recent and sophisticated model that uses a similar approach but also incorporates mutation frequency has recently been published. This paper was significant because the model allows for determining ancestral population sizes over time using the genome of only one individual. [You then describe the PSMC method.]”

I am therefore struggling to understand how the passage we are discussing — the one in italics above — could be a “summary of the field as a whole“ including linkage disequilibrium and PSMC methods. It seems to just be about the allele frequency method. You clearly distinguish the allele frequency method from the other methods. You say that the linkage disequilibrium method is “an independent way to check our results using allele diversity alone.“ You say it gives “the same result we obtained when using allele diversity alone“. You describe the PSMC methods as “A more recent and sophisticated model“.

I am sorry that I am spending so long on this point — this really is not where I had expected our discussion to go. I thought I was making a very straightforward request when I asked for a citation for the calculations in this passage. I am still hoping that you may be able to, now I have reminded you of the context of the passage. I appreciate that it may be a while since you re-read the chapter for yourself, and your recollection of what you wrote could be different from the text of the book. I know that I am sometimes surprised when I re-read something that I wrote myself after several months away from it.

If it’s not clear exactly what’s going on here, Buggs has cited and quoted specific passages and phrases in Adam and the Genome where Venema claims that “allele diversity alone” establishes that humanity never went through a bottleneck of two individuals, but rather had a large ancestral population size of thousands of individuals. As a scientist, Buggs wants to interact with this scientific claim, but in order to do so he needs to be able to see the original study (or studies).

Venema instead alludes to the state of the entire field. But citing the entire field won’t do because in Adam and the Genome, Venema made a specific claim about a specific type of data (allelic diversity) indicating a specific result (humans descended from a ~10,000 individual ancestral population).

Considering Zhao’s Paper

Venema later cited another paper, Zhao et al. (2000), to claim that human genetic diversity could not be traced back to just two individuals in the recent past. It didn’t solve the problem.

This paper looked at variants in human chromosome 22 and concluded “no severe bottleneck during the evolution of modern non-Africans.” But Richard Buggs provided a careful analysis of this paper in response, and offered multiple reasons why it too does not support Venema’s claims. In short, Zhao’s methods assume a constant, large population rather than actually testing it. When Buggs and others used their data to test the hypothesis that humanity went through a small bottleneck of two individuals, he reported that indeed their data do not exclude Adam and Eve. Buggs writes, “the time to the coalescent of 4 alleles [i.e., 2 individuals with 2 variant alleles each] will be a quarter of this time, this means a bottleneck [of 2 individuals] could have occurred between 178000 and 528000 years ago.” He concludes, “it seems to me very clear that this paper does not support your case.”

In response, Venema conceded Buggs’s point that Zhao et al. (2000) does not refute the hypothesis that humanity descends from a single couple:

I agree that Zhao (2000) does not support the case I make in Adam and the Genome, in that it might be statistically possible to have the variation in their dataset come from 4 haplotypes less than 200,000 years ago.

Dr. Venema should be commended for his candor. But Zhao et al. (2000) represents a common theme we’re seeing in this conversation: The literature does not really test the idea of Adam and Eve and simply assumes that humans evolved through a large population. This suggests that scientifically, the jury is still out.

Though Venema has continued to double-down on his claim that the genetics-based refutation of Adam and Eve as the progenitors of modern humans is “heliocentric certain” — i.e., as scientifically strong as the fact that the Earth orbits the sun — it seems that a much more cautious and accurate conclusion is that the “Adam and Eve” hypothesis really has not yet been properly tested.

A Broken Record

We don’t need to look at every back and forth in the discussion because it goes further into the weeds, and it’s ongoing. Buggs closes with comments like this:

Clearly you have a study in mind that supports the passage in italics and also this paragraph from your blog. All I am requesting is that you share the reference with me. Sorry if I am starting to sound like a broken record!

And:

I think you are seeing things in the studies that are not there, as they never set out to test the bottleneck hypothesis.

So the question is: given that the scientific literature does not specifically address the question of whether or not humans have passed through a bottleneck of two, what further analyses are needed to address this question? This will take more work than just interpretation of the existing literature.

Eventually Venema admits, in a backhanded sort of way, that the question of the Adam and Eve has not been specifically addressed in the scientific literature — though he thinks the data can be interpreted to refute Adam and Eve, writing:

I disagree here. Even if the authors themselves do not specifically address it, the data certainly do.

Buggs replies that this is exactly his own point — no one has done the proper analysis in the scientific literature to test whether allelic diversity is compatible with a bottleneck of two individuals:

I agree that the genomic data presented in the existing literature are relevant, and sufficient, for an analysis to address the short sharp bottleneck hypothesis. But if the authors have not done an appropriate analysis, someone else needs to. As far as I can see this has not been done. This is what I am saying in my blog.

Buggs later summarizes the situation as follows:

I have to admit, I am bemused by this. I think that the allele counting method is one of the best methods available for detecting bottlenecks, and I think it is the biggest challenge to the bottleneck of two hypothesis. I think there is a really interesting discussion to be had here. It has come as a genuine surprise to me that you are not pointing me to a calculation, or a paper, or a textbook, or something else that clearly explains the derivation of a 10,000 effective population size figure.

Buggs writes a powerful closing comment on the topic:

I cannot underline enough how important this issue is. If you are making unsubstantiated or mistaken claims about science in your book, just lines after saying “given the importance of this question for many Christians”, I don‘t think it is just me who views that as quite a serious issue. This is why I am so keen to give you every opportunity to substantiate this passage.

After reviewing Venema’s attempts to answer Buggs’s request for scientific support for the passage, already quoted above, Buggs notes that  he posted “three simple questions for others to answer about” Venema’s arguments in Adam and the Genome:

Does the passage make you think that it is referring to a scientific study where a few genes have been selected and the number of alleles of those genes in current day human populations have been measured?

Does the passage make you think that someone has done calculations on these genes on a computer that have indicated that the ancestral population size for humans is around 10,000?

Does the passage make you think that this is a different method to the PSMC method?

Leading BioLogos scholar Ted Davis responded to these questions with “my answer to each of your three questions is, Yes.” Another reader concurred. Buggs then concluded by writing:

No one, so far, has defended your reading of the passage. This is making me think that your reading of the passage is what you wish you had written, rather than what you actually wrote.

And now in your latest posts you are saying:

“The paper that specifically undergirds the ‘pick a few genes’ part of the broad brush summary statement about allele methods is this one, which like PSMC, is a coalescent-based approach:

http://www.genetics.org/content/genetics/147/4/1977.full.pdf”

My first response was to think “Well, thank you, why didn‘t you say so before?“ But a quick skim of the paper convinces me that, again, this is not an adequate citation to support the passage we are discussing.

1) It was published before the Human Genome Project, and before we had “sequenced the DNA of thousands of humans”

2) Most of the genes (if we may loosely call a retrotransposon a “gene“) in the paper are monomorphic in the human population studied and a handful are dimorphic. Thus the maximum number of alleles at any locus in the study is two. The allele counting method as described in your book, and elaborated upon in your Part I blog, explicitly requires higher numbers of alleles.

So again, I don‘t think this is an adequate citation.

Dennis, I have to say the conclusion I am coming to is that you made a mistake in your book. If so, I would have huge respect for you if you were willing to admit it, then we could all move on and discuss the interesting science of the other methods you have written about, and the work that Steven Schaffner is doing. We all make mistakes, and those of us active in research are very used to having them forcibly pointed out to us when we get back peer review comments on our manuscripts and grant proposals. It is never much fun to have them pointed out, but part of being a good scientist is being willing to correct our mistakes and move on.

So where does this long exchange leave us?

An Unacknowledged Mistake?

First, Richard Buggs asked for citations of specific scientific studies to substantiate Dennis Venema’s claims that allelic diversity shows humans evolved from an ancestral population of 10,000 individuals and not from a bottleneck of two.

Over a variety of comments, Venema tried responding in three primary ways: (1) vaguely citing the state of the field as a whole, (2) citing specific papers that did not provide what Buggs requested, and (3) ambiguously denying that he had made the argument that “allele diversity alone” (his words in Adam and the Genome) reveal an ancestral human population size of ~10,000 individuals, and claiming he was referring to other methods.

Regarding (1), Buggs pointed out that this is obviously insufficient to establish the specific point Venema was making. Regarding (2), Buggs essentially showed that in the end, Venema had engaged in citation bluffing. And after painstaking analysis showing the textual construction of Venema’s argument, Buggs showed regarding (3) that Venema had in fact made the specific argument in Adam and the Genome that “allelic diversity alone” indicates a very large population of human ancestors. Venema needed to provide a citation to back up his claim. And he couldn’t.

Buggs didn’t go into this conversation expecting Venema to be unable to provide a citation. Buggs doesn’t have an ax to grind here and simply wanted to interact with Venema’s scientific claims. He reasonably sought more information, but was disappointed. Thus, he wrote at the end of his Nature Ecology & Evolution blog:

Whilst this issue may seem trivial to many readers, for large numbers of religious believers in the world, this is a critical issue. Do they really face a binary choice between accepting mainstream science and believing that humans have, at some point in their history, all descended from a single couple? I am open to the possibility that they do face this dilemma, but I need more evidence before I am persuaded.

It’s as if Buggs innocently pulled a thread, and pretty soon found Venema’s core argument unraveling.

It must be reiterated that this is an ongoing conversation, and that more probably will be said by the various sides.

It’s also important to realize that Venema’s claims about the ancestral human population size aren’t just a side point in Adam and the Genome. They’re perhaps the most important scientific claim in the book — central to his chapter about Adam and Eve. Indeed, immediately before he makes these claims, he notes “the importance of this question for many Christians.” Buggs advises admitting an honest mistake, and moving on. While no fun, as Buggs says, that sounds like good advice.

Image credit: A human couple, by Hans, via Pixabay.