Variação no relógio molecular dos primatas

sexta-feira, dezembro 22, 2017

Variation in the molecular clock of primates

Priya Moorjani a,b,1,2, Carlos Eduardo G. Amorim a,1, Peter F. Arndt c, and Molly Przeworski a,d,

Author Affiliations

a Department of Biological Sciences, Columbia University, New York, NY 10027;

b Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142;

c Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany;

d Department of Systems Biology, Columbia University, New York, NY 10027

Edited by David C. Page, Whitehead Institute, Cambridge, MA, and approved July 19, 2016 (received for review January 8, 2016)


Much of our understanding of the chronology of human evolution relies on a fixed “molecular clock”; that is, a constant rate of substitutions per unit time. To evaluate the validity of this assumption, we analyze whole-genome sequences from 10 primate species. We find that there is substantial variation in the molecular clock between apes and monkeys and that rates even differ within hominines. Importantly, not all mutation types behave similarly; notably, transitions at CpG sites exhibit a more clocklike behavior than other substitutions, presumably because of their nonreplicative origin. Thus, the mutation spectra, and not just the overall substitution rates, are changing across primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions.


Events in primate evolution are often dated by assuming a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life history traits, suggesting it should also be found among primates. Motivated by these considerations, we analyze whole genomes from 10 primate species, including Old World Monkeys (OWMs), New World Monkeys (NWMs), and apes, focusing on putatively neutral autosomal sites and controlling for possible effects of biased gene conversion and methylation at CpG sites. We find that substitution rates are up to 64% higher in lineages leading from the hominoid–NWM ancestor to NWMs than to apes. Within apes, rates are ∼2% higher in chimpanzees and ∼7% higher in the gorilla than in humans. Substitution types subject to biased gene conversion show no more variation among species than those not subject to it. Not all mutation types behave similarly, however; in particular, transitions at CpG sites exhibit a more clocklike behavior than do other types, presumably because of their nonreplicative origin. Thus, not only the total rate, but also the mutational spectrum, varies among primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions. Taking this approach, we estimate the human and chimpanzee divergence time is 12.1 million years,​ and the human and gorilla divergence time is 15.1 million years​.

molecular clock mutation rate primate evolution CpG transition rate human–ape divergence time


1P.M. and C.E.G.A. contributed equally to this work.

2To whom correspondence may be addressed. Email: or

Author contributions: P.M., C.E.G.A., and M.P. designed research; P.M., C.E.G.A., and M.P. performed research; P.M. and P.F.A. contributed new reagents/analytic tools; P.M., C.E.G.A., and M.P. analyzed data; and P.M., C.E.G.A., and M.P. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

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Freely available online through the PNAS open access option.