Over at the BioLogos Forum, a couple of scientists have taken on two new BIO-Complexity papers by Ola Hössjer, Ann Gauger, and Colin Reeves. The critics are Dennis Venema, biologist at Trinity Western University and a BioLogos Fellow, and Stephen Schaffner, a computational biologist at the Broad Institute.
In a series of two papers (Part 1 and 2) we explore what can be said about human history from the DNA variation we observe among us today. Population genetics has been used to infer that we share a common ancestry with apes, that most of our human ancestors emigrated from Africa 50,000 years ago, that they possibly had some mixing with Neanderthals, Denisovans and other archaic populations, and that the early Homo population was never smaller than a few thousand individuals. Population genetics uses mathematical principles for how the genetic composition of a population develops over time through various forces of change, such as mutation, natural selection, genetic drift, recombinations and migration. In this article (Part 1) we investigate the assumptions about this theory and conclude that it is full of gaps and weaknesses. We argue that a unique origin model where humanity arose from a single couple with created diversity seems to explain data at least as well, if not better. We finally propose an alternative simulation approach that could be used in order to validate such a model. The mathematical principles of this model are described in more detail in our second paper (Part 2).
Venema and Schaffner are unhappy with this. Read their full comments here and here. In a nutshell, Venema says of the first paper that it is “a (poor) attempt to argue for a predetermined conclusion that humans were specially created as a pair in the Middle East. It does not offer a mechanism to deal with the obvious problems of such an approach other than an appeal to ‘created diversity.'”
Schaffner complains of “many problems with the paper.” It “simply does not address the actual genetic evidence for a large ancestral population size,” he writes, adding that the “other strong piece of evidence that human genetic variation is the result of accumulated mutations is that it looks like accumulated mutations.” As for the second paper, it “strikes me as nuts.”
Invective aside, at least this is an attempt to engage the science. We asked Dr. Hössjer, Professor of Mathematical Statistics at Stockholm University, for his response, which he was kind enough to provide.
On Dennis Venema:
Venema basically criticizes the Middle East version of the unique origin model, saying the African DNA looks older than non-European DNA, both from single locus allele frequency statistics and from two locus linkage disequilibrium patterns. But we also point out that this is a drawback of the Middle East unique origin model (on the other hand we argue that a ME origin has other advantages, for instance less inbreeding depression). We offer some tentative explanations (reference 50, for instance) of why African DNA could look older even if humanity originated in the Middle East. Venema rules out these explanations as inadequate. This may very well be true, but it remains to be seen when the model is implemented.
On Stephen Schaffner:
Schaffner points out that reference 49 in the BIO-Complexty Part 1 paper (Wilson Sayres et al. PLOS Genetics, 2014) is not about low diversity of the Y-chromosomes. This surprises me. In fact, the opening sentence of the abstract reads, “The human Y-chromosome exhibits surprisingly low levels of genetic diversity.” As far as I understand the whole purpose of this paper is to a) say the low Y-diversity cannot be explained by a neutral model, b) offer an alternative explanation in terms of purifying selection that removes deleterious alleles and hence reduces diversity at such selected loci, and also at linked neutral loci (background selection). An argument for this is that background selection is more efficient for the Y-chromosome, since there are no recombinations. Thus linked neutral loci more easily follow the selective sweep of the non-deleterious allele that is selected for at the non-neutral locus. In the Part I paper we propose an alternative explanation for the low Y-chromosome diversity — that all men originate from a single ancestor.
As a next point, Schaffner criticizes the waiting time argument in Sanford et al. against human-chimp common ancestry. However, he doesn’t specify on what grounds he does so. I don’t regard this as a serious critique, since probably, Sanford et al were very generous in their modeling. If we include orphan genes and other structures that differ greatly between humans and chimps, the waiting time problem becomes even more of an issue.
Schaffner then argues that the diversity we see today looks like it was gradually accumulated, rather than being due to created diversity. In particular he refers to the 1/f shape of the allele frequency spectrum at low frequencies f. This is to say that there are many SNPs with a very small minor allele frequency f. It is true that there will be fewer SNPs with a very small minor allele frequency if humanity started from a couple with created diversity that lived very recently. On the other hand, if this couple lived further back in history, there has been less time for genetic drift to create very rare alleles. So this is only an argument against a recent single couple. Even so, I think it is incomplete, since there are a number of factors that influence the allele frequency spectrum. Even if the first couple lived very recently and the worldwide population then expanded fast (as we know it has), we will still see many rare alleles (see reference 24).
A related point: Schaffner argues that genomic regions with a high mutation rate have a higher diversity. This would indicate that most variation is gradually accumulated through germline mutations. It is true that this to some extent would be an argument against a recent first couple (not necessarily against an old first couple though), since there has not been enough time to accumulate germline mutations into large numbers. However, in my view, Schaffner would need to make this criticism much more detailed in order to convince. For instance, Nathaniel Jeanson argues in references 56-57 that a recent first couple is consistent with mitochondrial DNA variation — a region with a very high mutation rate. In view of this, there doesn’t seem to be any simple strong correlation between a high mutation rate and high diversity that violates a first recent couple. But ultimately this has to be tested for all types of chromosomes through simulations and real data validation.
Schaffner then goes on arguing that haplotype block boundaries are not due to single recombination events, but that they occur in clumps (recombination hotspots). This may very well be true. Indeed, in our first article (Paper I) we actually write that these boundaries are either due to single recombination events (indicating a recent first couple) or due to hotspots (indicating an older first couple or common descent). However, Ann Gauger has pointed out that chimps have very different block boundaries than humans as another argument against common descent.
Finally, Schaffner criticizes our second (Part 2) paper, saying that the model is too large, and the parameter space huge. There is some truth in this. It would not be a good idea to validate the whole model straightaway. It is better to fit a small subset of the model at first, and then successively add to it. This is exactly our working plan.
Regarding a couple of other BioLogos commenters, Hössjer adds: Benjamin Kirk’s argument “is more or less the same as Venema’s.” Chris Falter says that “pseudogenes and ERVs are additional arguments for common ancestry. I know Ann Gauger, Paul Nelson, and others would have a lot more to say here, but my understanding is that this is simply not true.”
To Dr. Hössjer’s fine response we might add a few thoughts. Remember, these papers are not intended to be the last word on human ancestry. Instead, they offer models being developed in order to be tested. What Venema pejoratively labels a “predetermined conclusion” is simply a hypothesis to be tested. His dismissive tone is unworthy. All scientific models test “predetermined conclusions.” That’s what a hypothesis is.
Moreover, initial “created diversity” is a legitimate, testable mechanism. We know how genetics works and we can decide whether (within the bounds of genetics) initial high diversity could account for present-day observations.
As for the Middle East origin hypothesis, if you read the papers you will see that they have a justification for it — namely that African populations look artificially old due to different recombination rates. And given that their model allows for all kinds of normal mutations to occur, it’s hard to see how it’s fair for Dr. Schaffner to say they that they ignore mutations. Their model incorporates mutations!
Unfortunately, these critics seem to want to kill off the proposed model before it’s even been fully implemented. Yet Dr. Venema complains of “predetermined conclusions.” Look who’s talking.
Photo: Parietal art, Cave of Altamira, Spain, by Rameessos (Own work) [Public domain], via Wikimedia Commons.