Mailund on the Internet

I read this paper in bed yesterday before going to sleep:

Doubts about complex speciation between humans and chimpanzees

Presgraves and Yi, Trends in Ecology & Evolution 2009

Abstract

Two patterns from large-scale DNA sequence data have been put forward as evidence that speciation between humans and chimpanzees was complex, involving hybridization and strong selection. First, divergence between humans and chimpanzees varies considerably across the autosomes. Second, divergence between humans and chimpanzees (but not gorillas) is markedly lower on the X chromosome. Here, we describe how simple speciation and neutral molecular evolution explain both patterns. In particular, the wide range in autosomal divergence is consistent with stochastic variation in coalescence times in the ancestral population; and the lower human–chimpanzee divergence on the X chromosome is consistent with species differences in the strength of male-biased mutation caused by differences in mating system. We also highlight two further patterns of divergence that are problematic for the complex speciation model. Our conclusions raise doubts about complex speciation between humans and chimpanzees.

Complex speciation between humans and chimpanzees

You might remember the Patterson et al. paper in Nature back in 2006, that argued for a complex speciation of humans and chimps: An early separation between the two, followed by a hybridization and then the extinction of one of the species ancestral to the hybrids.

The arguments for this theory were 1) large variation in divergence time along the autosomal chromosomes and 2) a much more recent divergence of the X chromosome compared to the autosomes.

Wakeley then argued that 1) at least didn’t need any complex speciation history.  The variation in divergence is actually as would be expected just from variation in coalescence times along the chromosomes, assuming a reasonably large effective population size of the human/chimp ancestor species.

As for 2), the coalescence process alone cannot explain the recent divergence of X chromosomes.  We do expect a more recent divergence of X chromosomes than autosomes, since the effective population size of X chromosomes is 3/4 of that of the autosomal chromosomes, but the divergence of the X chromosomes is less than what can be explained by this.

This could either be explained by selection on the X chromosome (which essentially reduces the effective population size and thus leads to a reduced divergence) or by the difference in mutation rate between males and females that would affect the X chromosome differently than the autosomes (reducing the difference between the two).

It is well known that there is a bias in mutation rate between males and females, having to do with the average number of genome replications per generation in males and females, respectively.  The details I won’t go into here (although they are pretty important for the post, the post would just get too long and I don’t want to loose the readers who already know this … I might write about it in a separate post another day…)

Anyway…

Selection is probably not likely.  It would require a pretty uniform selection across the X chromosome.  The male-biased mutation explanation sounds more reasonable.

A problem with both explanation, though – Patterson et al. argued in their reply – is that this weird pattern in X is only observed between human and chimp and not between human and gorilla (or chimp and gorilla).

If mutation-rate differences alone could explain the observed data, we would expect a consistent value for from the human–chimpanzee and human–gorilla divergence data, but estimates of are significantly different (P = 0.001). A high value of also cannot explain other important features in Table 1: the near-absence of sites on chromosome X that cluster humans and gorillas or chimpanzees and gorillas; or why human–gorilla divergence should not be reduced on chromosome X (such a reduction would be expected if high male mutation rate were responsible for low human–chimpanzee genetic divergence on chromosome X).

Lineage specific male biased mutation rate

The Presgraves and Yi paper argues that male biased mutation rate can explain the pattern after all.

True, the low divergence on X is only observed between humans and chimps and not between humans and gorillas, but if the strength of this bias is larger on the human and chimp lineages than on the gorilla lineage it could still be an explanation.

Chimps are very promiscuous, humans somewhat less so, while gorillas are polygynous.  This affects sperm production so chimps produce most sperm per ejaculation, gorillas the least and humans again inbetween.

With more sperm produced in humans and chimps than in gorillas, it is therefore conceivable that the mutation bias is stronger in chimps and humans than in gorillas.

So they estimate this bias per lineage and get exactly that result: the bias is strongest in chimps, intermediate in humans and weakest in gorillas:

With different male-biased mutation rate in the lineages, with much less bias in gorillas, there is nothing strange in a reduced divergence on X chromosomes between humans and chimps than between humans and gorillas.

Voilà!  No more need for a complex speciation history!

At least until the next paper…

–

1. Presgraves, D., & Yi, S. (2009). Doubts about complex speciation between humans and chimpanzees Trends in Ecology & Evolution DOI: 10.1016/j.tree.2009.04.007
2. Patterson N, Richter DJ, Gnerre S, Lander ES, & Reich D (2006). Genetic evidence for complex speciation of humans and chimpanzees. Nature, 441 (7097), 1103-8 PMID: 16710306
3. Wakeley J (2008). Complex speciation of humans and chimpanzees. Nature, 452 (7184) PMID: 18337768
4. Patterson, N., Richter, D., Gnerre, S., Lander, E., & Reich, D. (2008). Patterson et al. reply Nature, 452 (7184) DOI: 10.1038/nature06806

231-236=-5

During some random surfing I stumbled upon these two blog posts:

• Did Gen Suwa just save paleoanthropology?
• Miocene hominids and a crisis of confidence

both by John Hawks.

I found these interesting not least because he refers to a paper that we published earlier this year:

Hobolth A, Christensen OF, Mailund T, Schierup MH. 2007. Genomic relationships and speciation times of human, chimpanzee, and gorilla inferred from a coalescent hidden Markov model. PLoS Genet 3:e7. doi:10.1371/journal.pgen.0030007

That paper was mainly on a new statistical method for analysing speciation. A method that combined comparative genomics with population genetics through a model that joined hidden Markov models with coalescence theory. Of course, that is not really what caught people’s attention. What we did in the paper was to apply our new method on data from human, gorrilla, chimp and orangutan, and one result that came out of that was a very recent split between human and chimp; a split only 4.1 million years old.

We get a very resent speciation split between human and apes exactly because of the combined population genetics and genomics. If we only look at the genomic sequences, the distance between these will necessarily be larger than the distance between the species — it takes a while from the time a piece of DNA is in the same individual until it is two different individuals in separate species — and our method is able to estimate the speciation split from the genome split.

I’m not sure how well I am explaining this here. I gave a (not too technical) talk in the computer science department some months ago, maybe that explains it better:

(sorry about the quality of the slides here, it looks like slideshare messed up the fonts)

A few other studies of genomic data before our own also reported more recent speciation times of human and chimp than previously believed — moving the time from about 6-8 million years ago down to maybe 4-5 million years ago — so a recent divergence between human and chimp might not be too far fetch after all, but still, I think our estimate is a bit too recent.

This is also what John Hawks writes.

Why do we get such a recent divergence, then?

It is hard to say. The 4.1 million years is what comes out of applying our method on the (admittedly small) data we had. It is a very new method, however. There is a lot we do not take into account in it and there might be biases in it we haven’t fully understood yet.

We are currently working on improving the method and once we get more data — the orangutan has already been sequenced and is now being assemblied and the gorilla genome is in the process of being sequenced — we will redo our analysis. It will be interesting to see how that turns out.