Placing confidence limits on the molecular age of the human–chimpanzee divergence
- Sudhir Kumar*,†,‡,§,
- Alan Filipski*,†,§,
- Vinod Swarna*,
- Alan Walker¶,∥,**, and
- S. Blair Hedges¶,††
- *Center for Evolutionary Functional Genomics, Biodesign Institute, and †School of Life Sciences, Arizona State University, Tempe, AZ 85287-5301; ††National Aeronautics and Space Administration Astrobiology Institute, and Departments of ¶Biology and ∥Anthropology, Pennsylvania State University, University Park, PA 16802
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Contributed by Alan Walker, November 8, 2005
Abstract
Molecular clocks have been used to date the divergence of humans and chimpanzees for nearly four decades. Nonetheless, this date and its confidence interval remain to be firmly established. In an effort to generate a genomic view of the human–chimpanzee divergence, we have analyzed 167 nuclear protein-coding genes and built a reliable confidence interval around the calculated time by applying a multifactor bootstrap-resampling approach. Bayesian and maximum likelihood analyses of neutral DNA substitutions show that the human–chimpanzee divergence is close to 20% of the ape–Old World monkey (OWM) divergence. Therefore, the generally accepted range of 23.8–35 millions of years ago for the ape–OWM divergence yields a range of 4.98–7.02 millions of years ago for human–chimpanzee divergence. Thus, the older time estimates for the human–chimpanzee divergence, from molecular and paleontological studies, are unlikely to be correct. For a given the ape–OWM divergence time, the 95% confidence interval of the human–chimpanzee divergence ranges from –12% to 19% of the estimated time. Computer simulations suggest that the 95% confidence intervals obtained by using a multifactor bootstrap-resampling approach contain the true value with >95% probability, whether deviations from the molecular clock are random or correlated among lineages. Analyses revealed that the use of amino acid sequence differences is not optimal for dating human–chimpanzee divergence and that the inclusion of additional genes is unlikely to narrow the confidence interval significantly. We conclude that tests of hypotheses about the timing of human–chimpanzee divergence demand more precise fossil-based calibrations.
Footnotes
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↵ ‡ To whom correspondence may be addressed at: The Biodesign Building A-240, Arizona State University, Tempe, AZ 85287-5301. E-mail: s.kumar{at}asu.edu. **To whom correspondence may be addressed. E-mail: axw8{at}psu.edu.
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↵ § S.K. and A.F. contributed equally to this work.
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Author contributions: S.K., A.W., and S.B.H. designed research; A.F. performed research; S.K. contributed new analytic tools; V.S. analyzed data; and A.W., S.B.H., and S.K. wrote the paper.
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Conflict of interest statement: No conflicts declared.
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Abbreviations: ML, maximum likelihood; C.I., confidence interval; MBR, multifactor bootstrap resampling; Ma, millions of years ago; RTTM, root-to-tip mean; OWM, Old World monkey; GTR, general time reversible; JTT, Jones–Taylor–Thornton.
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Freely available online through the PNAS open access option.
- Copyright © 2005, The National Academy of Sciences





