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Proc Natl Acad Sci U S A. 2016 Sep 20;113(38):10607-12. doi: 10.1073/pnas.1600374113. Epub 2016 Sep 6.

Variation in the molecular clock of primates.

Author information

1
Department of Biological Sciences, Columbia University, New York, NY 10027; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142; pm2730@columbia.edu mp3284@columbia.edu.
2
Department of Biological Sciences, Columbia University, New York, NY 10027;
3
Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany;
4
Department of Biological Sciences, Columbia University, New York, NY 10027; Department of Systems Biology, Columbia University, New York, NY 10027 pm2730@columbia.edu mp3284@columbia.edu.

Abstract

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​.

KEYWORDS:

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

PMID:
27601674
PMCID:
PMC5035889
DOI:
10.1073/pnas.1600374113
[Indexed for MEDLINE]
Free PMC Article

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