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A molecular timescale for vertebrate evolution


A timescale is necessary for estimating rates of molecular and morphological change in organisms and for interpreting patterns of macroevolution and biogeography1,2,3,4,5,6,7,8,9. Traditionally, these times have been obtained from the fossil record, where the earliest representatives of two lineages establish a minimum time of divergence of these lineages10. The clock-like accumulation of sequence differences in some genes provides an alternative method11 by which the mean divergence time can be estimated. Estimates from single genes may have large statistical errors, but multiple genes can be studied to obtain a more reliable estimate of divergence time1,12,13. However, until recently, the number of genes available for estimation of divergence time has been limited. Here we present divergence-time estimates for mammalian orders and major lineages of vertebrates, from an analysis of 658 nuclear genes. The molecular times agree with most early (Palaeozoic) and late (Cenozoic) fossil-based times, but indicate major gaps in the Mesozoic fossil record. At least five lineages of placental mammals arose more than 100 million years ago, and most of the modern orders seem to have diversified before the Cretaceous/Tertiary extinction of the dinosaurs.

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Figure 1: Estimation of divergence times.
Figure 2: Histograms (ai) of distributions of single-gene divergence times for nine multigene time estimates, and graphs (jl) of the effects of increased stringency of the rate-constancy test (corresponding to areas of 5% (recommended), 10%, 20%, and 50%, of the χ2 rejection curve) for the same divergences.
Figure 3: A molecular timescale for vertebrate evolution.
Figure 4: Comparison of fossil-based and molecular estimates of divergence time in vertebrates.


  1. 1

    Wilson, A. C., Carlson, S. S. & White, T. J. Biochemical evolution. Annu. Rev. Biochem. 46, 573–639 (1977).

    CAS  Article  Google Scholar 

  2. 2

    Nei, M. Molecular Evolutionary Genetics (Columbia Univ. Press, New York, 1987).

    Google Scholar 

  3. 3

    Novacek, M. J. Mammalian phylogeny: shaking the tree. Nature 356, 121–125 (1992).

    ADS  CAS  Article  Google Scholar 

  4. 4

    Martin, R. D. Primate origins: plugging the gaps. Nature 363, 223–234 (1993).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Avise, J. C. Molecular Markers, Natural History and Evolution (Chapman & Hall, New York, 1994).

    Book  Google Scholar 

  6. 6

    Hallam, A. An Outline of Phanerozoic Biogeography (Oxford Univ. Press, New York, 1994).

    Google Scholar 

  7. 7

    Easteal, S., Collet, C. & Betty, D. The Mammalian Molecular Clock (R. G. Landes, Austin, TX, 1995).

    Google Scholar 

  8. 8

    Gerhart, J. & Kirschner, M. Cells, Embryos, and Evolution (Blackwell Scientific, Malden, Massachusetts, 1997).

    Google Scholar 

  9. 9

    Gee, H. Before the Backbone (Chapman & Hall, New York, NY, 1996).

    Google Scholar 

  10. 10

    Benton, M. J. The Fossil Record 2 (Chapman & Hall, London, 1993).

    Google Scholar 

  11. 11

    Zuckerkandl, E. On the molecular evolutionary clock. J. Mol. Evol. 26, 34–46 (1987).

    ADS  CAS  Article  Google Scholar 

  12. 12

    Hedges, S. B., Parker, P. H., Sibley, C. G. & Kumar, S. Continental breakup and the ordinal diversification of birds and mammals. Nature 381, 226–229 (1996).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Takezaki, N., Rzhetsky, A. & Nei, M. Phylogenetic test of the molecular clock and linearized tree. Mol. Biol. Evol. 12, 823–833 (1995).

    CAS  PubMed  Google Scholar 

  14. 14

    Benton, M. J. Vertebrate Paleontology (Chapman & Hall, New York, 1997).

    Book  Google Scholar 

  15. 15

    Archibald, J. D. Fossil evidence for a late Cretaceous origin of “hoofed” mammals. Science 272, 1150–1153 (1996).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Kielan-Jaworowska, Z. Interrelationships of Mesozoic mammals. Hist. Biol. 6, 185–202 (1992).

    Article  Google Scholar 

  17. 17

    Cooper, A. & Penny, D. Mass survival of birds across the Cretaceous-Tertiary boundary: molecular evidence. Science 275, 1109–1113 (1997).

    CAS  Article  Google Scholar 

  18. 18

    Kay, R. F., Ross, C. & Williams, B. A. Anthropoid origins. Science 275, 797–804 (1997).

    CAS  Article  Google Scholar 

  19. 19

    Ward, S. in Function, Phylogeny, and Fossils (eds Begun, D. R., Ward, C. V. & Rose, M. D.) 269–290 (Plenum, New York, 1997).

    Book  Google Scholar 

  20. 20

    Pilbeam, D. Genetic and morphological records of the Hominoidea and hominid origins: a synthesis. Mol. Phyl. Evol. 5, 155–168 (1996).

    CAS  Article  Google Scholar 

  21. 21

    Benefit, B. R. & McCrossin, M. L. Earliest known Old World monkey skull. Nature 388, 368–371 (1997).

    ADS  CAS  Article  Google Scholar 

  22. 22

    Jaeger, J.-J., Tong, H. & Denys, C. The age of the Mus-Rattus divergence: paleontological data compared with the molecular clock. C. R. Acad. Sci. Paris 302, 917–922 (1986).

    Google Scholar 

  23. 23

    Parker, P. H. An Improved Estimate of the Mouse-Rat Divergence Time and Rates of Amino Acid Substitution in Mammals and BirdsThesis, Pennsylvania State Univ.((1996).

    Google Scholar 

  24. 24

    Carroll, R. L. Vertebrate Paleontology and Evolution (W. H. Freeman and Co., New York, 1988).

    Google Scholar 

  25. 25

    Springer, M. S. et al. Endemic African mammals shake the phylogenetic tree. Nature 388, 61–63 (1997).

    CAS  Article  Google Scholar 

  26. 26

    Duret, L., Mouchiroud, D. & Gouy, M. HOVERGEN: a database of homologous vertebrate genes. Nucleic Acids Res. 22, 2360–2365 (1994).

    CAS  Article  Google Scholar 

  27. 27

    Tajima, F. Simple methods for testing the molecular evolutionary clock hypothesis. Genetics 135, 599–607 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Kumar, S., Tamura, K. & Nei, M. MEGA: Molecular Evolutionary Genetic Analysis (Pennsylvania State Univ., 1993).

    Google Scholar 

  29. 29

    Gheerbrant, E., Sudre, J. & Cappetta, H. APaleocene proboscidean from Morocco. Nature 383, 68–70 (1996).

    ADS  CAS  Article  Google Scholar 

  30. 30

    Benton, M. J. Phylogeny of the major tetrapod groups: morphological data and divergence dates. J. Mol. Evol. 30, 409–424 (1990).

    ADS  CAS  Article  Google Scholar 

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We thank L. Poling, A. Beausang, and R. Padmanabhan for assistance with sequence data retrieval; A. Beausang for artwork; A. G. Clark, C. A. Hass, I. Jakobsen, M. Nei, C. R. Rao, and A.Walker for comments and discussion; and L. Duret for instructions on use of the HOVERGEN database. This work was supported in part by grants to M. Nei (NIH and NSF) and S.B.H. (NSF).

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Correspondence to S. Blair Hedges.

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Kumar, S., Hedges, S. A molecular timescale for vertebrate evolution. Nature 392, 917–920 (1998).

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