Direct estimation of mutations in great apes reconciles phylogenetic dating

Pretty interesting new (paywalled) paper out in Nature Ecology and Evolution:

Direct estimation of mutations in great apes reconciles phylogenetic dating

The authors use parent-offspring trios of chimps, gorillas, and orangutans to estimate the per-generation mutation rate among different great apes. Then they use the well documented positive correlation between parent age and offspring mutation rate to estimate the per generation mutation rate among these great apes.

The results suggest that chimps, gorillas, and orangutans all have a similar mutation rate that is ~ 1/3 higher than the human rate. They suggest that a (relatively) recent slowdown in the rate of mutations in the human lineage may have occurred.

The authors also get divergence time estimates using the new rates that are earlier than previous results suggested by some whole genome analyses but more in line with fossil evidence:

Interesting stuff!

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Anyone? Bueller?

This stuff seems relevant to a lot of topics that people here are interested in! :slight_smile:

Assuming it’s possible to do with the website’s software, I’m happy to share a copy of the paper via PM.

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What do you or anyone else think of the ~10 million year date for the divergence of the chimp and human lineages?

What do you or anyone else think of the ~10 million year date for the divergence of the chimp and human lineages?

It’s well within the range of estimates seen previously, but the accuracy relies on previous estimates of effective population size, which I haven’t looked at.
Of note, the divergence time is earlier than the speciation time, since the former is an estimate of genome-wide coalescence, which occurred prior to complete genetic separation of the homo and pan lineages.

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Exactly. Does everyone follow? This is how incomplete lineage sorting happens too.

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As soon as it was explained I felt a bit embarrassed that I didn’t see it immediately. To use a really poor analogy, the American Irish population separated from the native Irish population a few hundred years ago, but an analysis of their genomes would point to a common ancestor that existed much earlier than the population split. Divergence since common ancestry would be present in each population at the moment of separation.

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As a non-biologist, that’s actually a very helpful analogy.

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That is, it appears to be an average coalescence time over the genome, and coalescents of each gene must predate the separation of the populations, sometimes by quite a lot.

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Yup, that’s a better way to put it.

Here’s another attempt. Suppose that the human population is split in two tomorrow, say Western Hemisphere from Eastern. Mitochondrial Eve for the two populations would at first be the same as for the combined population, thus coalescing hundreds of thousands of years ago, not now. As time goes on, lineage sorting will probably make that combined date a bit younger, but it’s never going to reach the present; the only way for that to happen is if the same haplotype becomes fixed in each new population, a very unlikely event.

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The paper is behind a paywall, but abstract makes the following points-

The yearly trio-based mutation rate estimate of around 0.43 × 10−9 markedly lower than previous indirect estimates of about 1 × 10−9 per year from phylogenetic comparisons of the great apes calibrated by fossil evidence.

The 0.43 values refers to direct measurements of per year mutation rates while the value 1 refers to measurements taking the fossil evidence as input.

The paper then gives the value of mutation rate per year for chimps at 1.48…

1.48 is more than three times.more than 0.43. how is it only 1/3rd more … I have seen other papers also give direct measurement of mutation rates for Humans at (1-1.2 X10 ^(-8))… which also comes to 0.4- 0.48 × 10^(−9)…

What am I missing here?
Also, a press release for the paper makes the following interesting claim-

The higher rates in apes have an impact on the length of time estimated to have passed since the common ancestor of humans and chimpanzees lived. This is because a higher mutation rate means that the number of genetic differences between humans and chimpanzees will accumulate over a shorter period.

If the new mutation rates for apes are applied, the researchers estimate that the speciation that separated humans from chimpanzees took place around 6.6 million years ago. If the mutation rate for humans is applied, speciation should have been around 10 million years ago

They seem to be making the claim that there is a difference of 3.6mya in prediction of the common ancestor die to the difference in rates. Is this correct?

It would be great if you can share the paper. I agree with you that it is related to a lot of the discussions going on here.
Edit:Human mutation rate has slowed recently -- ScienceDaily
Link to the press release I mentioned.

No, it gives the factor by which the chimps, gorillas, and orangutan mutation rates are greater than the measured human mutation rate as 1.48. The specific factor for chimps relative to humans was 1.50.

Table 1 reports the measured mutation rates in all the examined trios, where the average for the chimps was 1.26x10^8 per generation, when the average age of the parents was about 17.

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Yes, it stands to reason that if you use a mutation rate ~50% faster, then your molecular clock analysis will give you a date ~33% younger.

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Finally was able to find a prepublication version of the paper.
https://www.google.com/url?sa=t&source=web&rct=j&url=https://www.biorxiv.org/content/biorxiv/early/2018/03/23/287821.full.pdf&ved=2ahUKEwjlv5PE2LvhAhWZ6nMBHXdpCh0QFjABegQIBRAB&usg=AOvVaw1Hz5YusME6Dik0Ktmsg3ls

The give the following information -

  1. Absolute rate of mutation per billion years for Humans is 0.43. For chimps it is 0.72 (this is where the 30% difference comes from).
  2. Genetic divergence between humans and chimps is 0.0137, the human to CA length becomes 0.006713.
  3. They calculate the Human chimp divergence based on the chimp mutation rate of 0.72 as 9.46mya. They get a coalescence time of 3.5 Mya, and so predict speciation 5.96mya.

They don’t mention the human chimp divergence time in the scenario where human mutation rates don’t increase. But it’s simple to calculate with the data they provide.With mutation rates of 0.43 per billion years (or 0.00043 per million years), the divergence time becomes 15.6 Mya.

Hence the requirement for a higher rate earlier or a drop in rate in recent times.

@swamidass: Does this impact the argument you made about humans and chimp CAs converging at the same point? Wouldn’t a difference of 5 million years be problematic?

Ya… worked it out above…

The question is how does anyone justify a constant mutation rate over time for apes and a sudden variation in humans? Isn’t it a little arbitrary?

In the final paper, the figure for chimps is 0.64, which is where the ~50% difference comes from.

In the final paper, using the figure of 0.634 for the non-human primates, they estimated a divergence time between humans and chimps of 10.6Ma (in their figure they have 10.88 in the methods section for some reason). Yes, if you use the human mutation rate which is about 50% lower, then the divergence time increases by about 50% to about 15.7Ma.

When you plot mutation rates on the great ape phylogeny, humans are the outliers, while chimps, gorillas, and orangutans are all fairly consistent (as the abstract notes). It’s far more parsimonious to invoke a single change in mutation rates than 3+.

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Ok thanks . The abstract puts out a number close to 1.5 as the mutation rate per year for chimps based on direct measurement… how did they come to 0.64 per billion . Shouldn’t it be 1.5 per billion years.
That’s one thing I didn’t get.

Wouldn’t it be parsimonious to say any of the following -
a) They don’t share a common ancestor.
b) Neutral models cannot explain human evolution. There could have been some selection intensive periods where more mutations got fixed.

I get why they wouldn’t go for a( because of other lines of evidence supporting CA). But why not for b?

Again, this 1.5 is the FACTOR by which the chimpanzee mutation rate is higher than the human rate. 0.43 x 1.5 = 0.64

Extrapolating the relationship between the mutation rate and the age of parents from humans to these other great apes, we estimated that each species has higher mutation rates per year by factors of 1.50 ± 0.10, 1.51 ± 0.23, and 1.42 ± 0.22 for chimpanzee, gorilla, and orangutan, respectively

No, because that would mean throwing out mountains of evidence.

No, because even in such “selection intensive periods”, that wouldn’t affect the accumulation of the vast majority of mutations because most mutations are neutral.

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Ok got it… thanks… that was bugging me… I missed the “factor” in there.

So the only way out is a change in mutation rate…
seems fair enough.

Ashwin seems to be of the impression that the idea of changing mutation rates is some ad-hoc conjecture invented to make data fit a particular hypothesis.

But changes in mutation rates are observed to happen in experiments. There’s nothing implausible or intrinsically unlikely about it. Within certain limits of course.

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