We just published a new paper a few days ago title Strong Selective Sweeps on the X Chromosome in the Human-Chimpanzee Ancestor Explain Its Low Divergence
The human and chimpanzee X chromosomes are less divergent than expected based on autosomal divergence. We study incomplete lineage sorting patterns between humans, chimpanzees and gorillas to show that this low divergence can be entirely explained by megabase-sized regions comprising one-third of the X chromosome, where polymorphism in the human-chimpanzee ancestral species was severely reduced. We show that background selection can explain at most 10% of this reduction of diversity in the ancestor. Instead, we show that several strong selective sweeps in the ancestral species can explain it. We also report evidence of population specific sweeps in extant humans that overlap the regions of low diversity in the ancestral species. These regions further correspond to chromosomal sections shown to be devoid of Neanderthal introgression into modern humans. This suggests that the same X-linked regions that undergo selective sweeps are among the first to form reproductive barriers between diverging species. We hypothesize that meiotic drive is the underlying mechanism causing these two observations.
We’ve been working on the differences between the autosomes and the X chromosome for a little while now, but this work actually started earlier than this, while we were working on the gorilla genome analysis.
There was an interesting observation made by Patterson et al. (2006) that the divergence between humans and chimpanzees is much lower on the X chromosome than on the autosomes, even taking into account the smaller effective population size on the X chromosome in the common ancestor. They interpreted this, combined with seeing a large variation on coalescence times on the autosomes, as suggestive of strong population structure in the ancestral species, in particular as suggestive that the human ancestor was admixed between a lineage closely related to the chimpanzee ancestor and another lineage that diverged earlier from the chimpanzee.
Most of the patterns they observed could also be explained by just having a very large effective population size in the ancestral species, but the difference in divergence between the autosomes and the X chromosome was still a puzzle.
The X divergence is simply too small compared to the expectation from just having an effective population size of 3/4 on the X chromosome compared to the autosomes (there are only 3/4 as many X chromosomes as autosomes in a population (assuming the same number of males and females) and while different breeding success in males and females is expected to deviate from the 3/4 somewhat the divergence is really very small for that to be the explanation — especially considering that we don’t see that large differences elsewhere in great apes).
While working on the gorilla genome paper we used our coalescent hidden Markov model approach to examine this. The CoalHMM lets us look at incomplete lineage sorting along the genome which is a strong proxy for the diversity in the ancestral species. And while we clearly saw the reduced divergence on the X chromosome between humans and chimpanzees we also clearly saw a reduction in ILS — something also observed in the Patterson et al. paper — suggesting that the explanation is not a lower mutation rate but reduced diversity in the ancestral species.
Interestingly, we observed that this reduction in ILS was not uniform along the X chromosome. This is what we have studied in greater detail in the new paper.
What we see is that the ancestral diversity on the X chromosome looks bimodal. On some parts of the X chromosome we see the 3/4 diversity we would expect and in other parts of the chromsome it is much reduced compared to that.
Selection is expected to reduce diversity. Purifying selection removes diversity because deleterious mutations are purged from the population and positive selection creates a sweep where part of the genome has coalesced very recently.
Very wide regions with low diversity is hard to create by purifying selection — it depends a little on the math and the assumptions that goes into the models, but generally we don’t expect it based on the models we have and we don’t see it when we try to simulate the effect of such selection.
Positive selection — selective sweeps — can create it, but very wide regions as those we observe require either very strong sweeps or recurrent sweeps.
Whatever creates it, it is clearly there, and that is a bit of a puzzle.
We couldn’t really come up with any explanation for the pattern we see except for strong selection. That doesn’t mean that it is selection, of course, but we are completely blank on what it could be if it isn’t.
We don’t really have an explanation for it in the paper. We don’t really have an explanation, period, actually. We do provide a hypothesis for something it could be, but we don’t have any strong evidence for it, so it is something we are still working on figuring out.
Our results do not rule out the complex speciation scenario suggested by Patterson et al. Hybrid incompatibility could be the selection that we are observing, and very interestingly the regions we see the reduced ancestral divergence in are exactly the regions where we see no Neanderthal introgression in non-African modern humans which suggests it could be the same mechanism we see in the human-chimpanzee ancestor.
However, we also see reduced diversity in extant great apes in the same regions so unless there is hybridisation and barriers against gene flow in these regions everywhere in the great ape phylogeny, there is something more complicated — and more interesting — going on.
We are now trying to figure out what that could be.