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Molecular clocks: four decades of evolution

Abstract

During the past four decades, the molecular-clock hypothesis has provided an invaluable tool for building evolutionary timescales, and has served as a null model for testing evolutionary and mutation rates in different species. Molecular clocks have also influenced the development of theories of molecular evolution. As DNA-sequencing technologies have progressed, the use of molecular clocks has increased, with a profound effect on our understanding of the temporal diversification of species and genomes.

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Figure 1: Assessing the similarity of evolutionary rates among lineages.
Figure 2: Growth in the size of the DNA databanks and the use of the molecular clock.

References

  1. Hagen, J. B. The origins of bioinformatics. Nature Rev. Genet. 1, 231–236 (2000).

    CAS  PubMed  Google Scholar 

  2. Sanger, F. Chemistry of insulin; determination of the structure of insulin opens the way to greater understanding of life processes. Science 129, 1340–1344 (1959).

    CAS  PubMed  Google Scholar 

  3. Zuckerkandl, E. & Pauling, L. in Horizons in Biochemistry (eds Kasha, M. & Pullman, B.) 189–225 (Academic Press, New York, 1962).

    Google Scholar 

  4. Morgan, G. J. Emile Zuckerkandl, Linus Pauling, and the molecular evolutionary clock, 1959–1965. J. Hist. Biol. 31, 155–178 (1998).

    CAS  PubMed  Google Scholar 

  5. Margoliash, E. Primary structure and evolution of cytochrome c. Proc. Natl Acad. Sci. USA 50, 672–679 (1963).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Doolittle, R. F. & Blomback, B. Amino-acid sequence investigations of fibrinopeptides from various mammals: evolutionary implications. Nature 202, 147–152 (1964).

    CAS  PubMed  Google Scholar 

  7. Simpson, G. G. Organisms and molecules in evolution. Science 146, 1535–1538 (1964).

    CAS  PubMed  Google Scholar 

  8. Aronson, J. D. 'Molecules and monkeys': George Gaylord Simpson and the challenge of molecular evolution. Hist. Philos. Life. Sci. 24, 441–465 (2002).

    PubMed  Google Scholar 

  9. Zuckerkandl, E. & Pauling, L. in Evolving Genes and Proteins (eds Bryson, V. & Vogel, H. J.) 97–166 (Academic Press, New York, 1965).

    Google Scholar 

  10. Goodman, M. Evolution of the catarrhine primates at the macromolecular level. Primates Med. 1, 10–26 (1968).

    CAS  PubMed  Google Scholar 

  11. Goodman, M. Serological analysis of the systematics of recent hominoids. Hum. Biol. 35, 377–436 (1963).

    CAS  PubMed  Google Scholar 

  12. Goodman, M., Moore, G. W. & Matsuda, G. Darwinian evolution in the genealogy of haemoglobin. Nature 253, 603–608 (1975).

    CAS  PubMed  Google Scholar 

  13. Sarich, V. M. & Wilson, A. C. Rates of albumin evolution in primates. Proc. Natl Acad. Sci. USA. 58, 142–148 (1967).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  15. Easteal, S., Collet, C. & Betty, D. The Mammalian Molecular Clock (R.G. Landes, New York, 1995).

    Google Scholar 

  16. Margoliash, E. & Smith, E. L. in Evolving Genes and Proteins (eds Bryson, V. & Vogel, H. J.) 221–242 (Academic Press, New York, 1965).

    Google Scholar 

  17. Hartl, D. & Dykhuizen, D. A selectively driven molecular clock. Nature 281, 230–231 (1979).

    CAS  PubMed  Google Scholar 

  18. Goodman, M., Braunitzer, G., Stangl, A. & Schrank, B. Evidence on human origins from haemoglobins of African apes. Nature 303, 546–548 (1983).

    CAS  PubMed  Google Scholar 

  19. Kimura, M. Evolutionary rate at the molecular level. Nature 217, 624–626 (1968).

    CAS  PubMed  Google Scholar 

  20. Kimura, M. The Neutral Theory of Molecular Evolution (Cambridge Univ. Press, 1983).

    Google Scholar 

  21. King, J. L. & Jukes, T. H. Non-Darwinian evolution. Science 164, 788–798 (1969).

    CAS  PubMed  Google Scholar 

  22. Laird, C. D., McConaughy, B. L. & McCarthy, B. J. Rate of fixation of nucleotide substitutions in evolution. Nature 224, 149–154 (1969).

    CAS  PubMed  Google Scholar 

  23. Britten, R. J. & Kohne, D. E. Repeated sequences in DNA. Hundreds of thousands of copies of DNA sequences have been incorporated into the genomes of higher organisms. Science 161, 529–540 (1968).

    CAS  PubMed  Google Scholar 

  24. Diamond, J. M. Taxonomy by nucleotides. Nature 305, 17–18 (1983).

    CAS  PubMed  Google Scholar 

  25. Kohne, D. E. Evolution of higher-organism DNA. Q. Rev. Biophys. 3, 327–375 (1970).

    CAS  PubMed  Google Scholar 

  26. Kumar, S. & Subramanian, S. Mutation rates in mammalian genomes. Proc. Natl Acad. Sci. USA 99, 803–808 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Yi, S., Ellsworth, D. L. & Li, W. H. Slow molecular clocks in Old World monkeys, apes, and humans. Mol. Biol. Evol. 19, 2191–2198 (2002).

    CAS  PubMed  Google Scholar 

  28. Dickerson, R. E. The structures of cytochrome c and the rates of molecular evolution. J. Mol. Evol. 1, 26–45 (1971).

    CAS  PubMed  Google Scholar 

  29. Ohta, T. & Kimura, M. On the constancy of evolutionary rate of cistron. J. Mol. Evol. 1, 18–25 (1971).

    CAS  Google Scholar 

  30. Langley, C. H. & Fitch, W. M. An examination of the constancy of the rate of molecular evolution. J. Mol. Evol. 3, 161–177 (1974).

    CAS  PubMed  Google Scholar 

  31. Fitch, W. M. in Molecular Evolution (ed. Ayala, F. J.) 160–178 (Sinauer Associates, Sunderland, Massachusetts, 1976).

    Google Scholar 

  32. Gillespie, J. H. & Langley, C. H. Are evolutionary rates really variable? J. Mol. Evol. 13, 27–34 (1979).

    CAS  PubMed  Google Scholar 

  33. Gillespie, J. H. The molecular clock may be an episodic clock. Proc. Natl Acad. Sci. USA 81, 8009–8013 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Takahata, N. On the overdispersed molecular clock. Genetics 116, 169–179 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  36. Nei, M., Xu, P. & Glazko, G. Estimation of divergence times from multiprotein sequences for a few mammalian species and several distantly related organisms. Proc. Natl Acad. Sci. USA 98, 2497–2502 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Gu, X. & Li, W. H. Higher rates of amino acid substitution in rodents than in humans. Mol. Phylogenet. Evol. 1, 211–214 (1992).

    CAS  PubMed  Google Scholar 

  38. Ayala, F. J. Vagaries of the molecular clock. Proc. Natl Acad. Sci. USA. 94, 7776–7783 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Wang, D. Y., Kumar, S. & Hedges, S. B. Divergence time estimates for the early history of animal phyla and the origin of plants, animals and fungi. Proc. R. Soc. Lond. B 266, 163–171 (1999).

    CAS  Google Scholar 

  40. Tamura, K., Subramanian, S. & Kumar, S. Temporal patterns of fruit fly (Drosophila) evolution revealed by mutation clocks. Mol. Biol. Evol. 21, 36–44 (2004).

    CAS  PubMed  Google Scholar 

  41. Doolittle, R. F., Feng, D. F., Tsang, S., Cho, G. & Little, E. Determining divergence times of the major kingdoms of living organisms with a protein clock. Science 271, 470–477 (1996).

    CAS  PubMed  Google Scholar 

  42. Hedges, S. B. et al. A genomic timescale for the origin of eukaryotes. BMC Evol. Biol. 1, 4 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Mayr, E. Animal Species and Evolution (Cambridge Univ. Press, New York, 1963).

    Google Scholar 

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

    Google Scholar 

  45. Coyne, J. A. & Orr, H. A. Speciation (Sinauer Associates, Sunderland, Massachusetts, 2004).

    Google Scholar 

  46. Kimura, M. Preponderance of synonymous changes as evidence for the neutral theory of molecular evolution. Nature 267, 275–276 (1977).

    CAS  PubMed  Google Scholar 

  47. Miyata, T. & Yasunaga, T. Molecular evolution of mRNA: a method for estimating evolutionary rates of synonymous and amino acid substitutions from homologous nucleotide sequences and its application. J. Mol. Evol. 16, 23–36 (1980).

    CAS  PubMed  Google Scholar 

  48. Wu, C. I. & Li, W. H. Evidence for higher rates of nucleotide substitution in rodents than in man. Proc. Natl Acad. Sci. USA 82, 1741–1745 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Britten, R. J. Rates of DNA sequence evolution differ between taxonomic groups. Science 231, 1393–1398 (1986).

    CAS  PubMed  Google Scholar 

  50. Li, W. H. So, what about the molecular clock hypothesis? Curr. Opin. Genet. Dev. 3, 896–901 (1993).

    CAS  PubMed  Google Scholar 

  51. Martin, A. P. & Palumbi, S. R. Body size, metabolic rate, generation time, and the molecular clock. Proc. Natl Acad. Sci. USA 90, 4087–4091 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Bromham, L. Molecular clocks in reptiles: life history influences rate of molecular evolution. Mol. Biol. Evol. 19, 302–309 (2002).

    CAS  PubMed  Google Scholar 

  53. Martin, A. P., Naylor, G. J. & Palumbi, S. R. Rates of mitochondrial DNA evolution in sharks are slow compared with mammals. Nature 357, 153–155 (1992).

    CAS  PubMed  Google Scholar 

  54. Bromham, L., Rambaut, A. & Harvey, P. H. Determinants of rate variation in mammalian DNA sequence evolution. J. Mol. Evol. 43, 610–621 (1996).

    CAS  PubMed  Google Scholar 

  55. Huttley, G. A., Jakobsen, I. B., Wilson, S. R. & Easteal, S. How important is DNA replication for mutagenesis? Mol. Biol. Evol. 17, 929–937 (2000).

    CAS  PubMed  Google Scholar 

  56. Hwang, D. G. & Green, P. Bayesian Markov chain Monte Carlo sequence analysis reveals varying neutral substitution patterns in mammalian evolution. Proc. Natl Acad. Sci. USA 101, 13994–14001 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Ellegren, H., Smith, N. G. & Webster, M. T. Mutation rate variation in the mammalian genome. Curr. Opin. Genet. Dev. 13, 562–568 (2003).

    CAS  PubMed  Google Scholar 

  58. Feng, D. F., Cho, G. & Doolittle, R. F. Determining divergence times with a protein clock: update and reevaluation. Proc. Natl Acad. Sci. USA 94, 13028–13033 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Wray, G. A., Levinton, J. S. & Shapiro, L. H. Molecular evidence for deep Precambrian divergences among metazoan phyla. Science 274, 568–573 (1996).

    CAS  Google Scholar 

  60. 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).

    CAS  PubMed  Google Scholar 

  61. Hedges, S. B. & Kumar, S. Genomic clocks and evolutionary timescales. Trends Genet. 19, 200–206 (2003).

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  63. Springer, M. S. et al. Endemic African mammals shake the phylogenetic tree. Nature 388, 61–64 (1997).

    CAS  PubMed  Google Scholar 

  64. Hedges, S. B. Afrotheria: plate tectonics meets genomics. Proc. Natl Acad. Sci. USA 98, 1–2 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Archibald, J. D., Averianov, A. O. & Ekdale, E. G. Late Cretaceous relatives of rabbits, rodents, and other extant eutherian mammals. Nature 414, 62–65 (2001).

    CAS  PubMed  Google Scholar 

  66. Archibald, J. D. Fossil evidence for a Late Cretaceous origin of 'hoofed' mammals. Science 272, 1150–1153 (1996).

    CAS  PubMed  Google Scholar 

  67. Archibald, J. D. Divergence times of eutherian mammals. Science 285, 2031 (1999).

    Google Scholar 

  68. Benton, M. J. Vertebrate Palaeontology (Blackwell Science, Oxford, 2000).

    Google Scholar 

  69. Tavare, S., Marshall, C. R., Will, O., Soligo, C. & Martin, R. D. Using the fossil record to estimate the age of the last common ancestor of extant primates. Nature 416, 726–729 (2002).

    CAS  PubMed  Google Scholar 

  70. Clarke, J. A., Tambussi, C. P., Noriega, J. I., Erickson, G. M. & Ketcham, R. A. Definitive fossil evidence for the extant avian radiation in the Cretaceous. Nature 433, 305–308 (2005).

    CAS  PubMed  Google Scholar 

  71. Asher, R. J. et al. Stem lagomorpha and the antiquity of Glires. Science 307, 1091–1094 (2005).

    CAS  PubMed  Google Scholar 

  72. Foote, M. & Sepkoski, J. J. Jr. Absolute measures of the completeness of the fossil record. Nature 398, 415–417 (1999).

    CAS  PubMed  Google Scholar 

  73. Feduccia, A. The Origin and Evolution of Birds (Yale Univ. Press, New Haven, 1999).

    Google Scholar 

  74. Ayala, F. J. & Rzhetsky, A. Origin of the metazoan phyla: molecular clocks confirm paleontological estimates. Proc. Natl Acad. Sci. USA 95, 606–611 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Gu, X. Early metazoan divergence was about 830 million years ago. J. Mol. Evol. 47, 369–371 (1998).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Bromham, L., Penny, D., Rambaut, A. & Hendy, M. D. The power of relative rates tests depends on the data. J. Mol. Evol. 50, 296–301 (2000).

    CAS  PubMed  Google Scholar 

  78. Bromham, L. & Penny, D. The modern molecular clock. Nature Rev. Genet. 4, 216–224 (2003).

    CAS  PubMed  Google Scholar 

  79. Li, W. H. & Tanimura, M. The molecular clock runs more slowly in man than in apes and monkeys. Nature 326, 93–96 (1987).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  81. Nei, M. & Kumar, S. Molecular Evolution and Phylogenetics (Oxford Univ. Press, New York, 2000).

    Google Scholar 

  82. Hasegawa, M. & Kishino, H. Heterogeneity of tempo and mode of mitochondrial DNA evolution among mammalian orders. Jpn. J. Genet. 64, 243–258 (1989).

    CAS  PubMed  Google Scholar 

  83. Kishino, H. & Hasegawa, M. Converting distance to time: application to human evolution. Methods Enzymol. 183, 550–570 (1990).

    CAS  PubMed  Google Scholar 

  84. Uyenoyama, M. K. A generalized least-squares estimate for the origin of sporophytic self-incompatibility. Genetics 139, 975–992 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Sanderson, M. J. A nonparametric approach to estimating divegence times in the absence of rate constancy. Mol. Biol. Evol. 14, 1218–1232 (1997).

    CAS  Google Scholar 

  86. Gillespie, J. H. The Causes of Molecular Evolution (Oxford Univ. Press, New York, 1991).

    Google Scholar 

  87. Thorne, J. L., Kishino, H. & Painter, I. S. Estimating the rate of evolution of the rate of molecular evolution. Mol. Biol. Evol. 15, 1647–1657 (1998).

    CAS  PubMed  Google Scholar 

  88. Holder, M. & Lewis, P. O. Phylogeny estimation: traditional and Bayesian approaches. Nature Rev. Genet. 4, 275–284 (2003).

    CAS  PubMed  Google Scholar 

  89. Yang, Z. A heuristic rate smoothing procedure for maximum likelihood estimation of species divergence time. Acta Zool. Sinica 50, 645–656 (2004).

    Google Scholar 

  90. Springer, M. S., Murphy, W. J., Eizirik, E. & O'Brien, S. J. Placental mammal diversification and the Cretaceous–Tertiary boundary. Proc. Natl Acad. Sci. USA. 100, 1056–1061 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Hasegawa, M., Thorne, J. L. & Kishino, H. Time scale of eutherian evolution estimated without assuming a constant rate of molecular evolution. Genes Genet. Syst. 78, 267–283 (2003).

    CAS  PubMed  Google Scholar 

  92. Smith, A. B. & Peterson, K. J. Dating the time of origin of major clades: molecular clocks and the fossil record. Annu. Rev. Earth Planet. Sci. 30, 65–88 (2002).

    CAS  Google Scholar 

  93. Morris, S. C. Evolution: bringing molecules into the fold. Cell 100, 1–11 (2000).

    CAS  PubMed  Google Scholar 

  94. Aris-Brosou, S. & Yang, Z. Bayesian models of episodic evolution support a Late Precambrian explosive diversification of the Metazoa. Mol. Biol. Evol. 20, 1947–1954 (2003).

    CAS  PubMed  Google Scholar 

  95. Peterson, K. J. et al. Estimating metazoan divergence times with a molecular clock. Proc. Natl Acad. Sci. USA 101, 6536–6541 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Blair, J. E. & Hedges, S. B. Molecular clocks do not support the Cambrian explosion. Mol. Biol. Evol. 22, 387–390 (2005).

    CAS  PubMed  Google Scholar 

  97. Hedges, S. B., Blair, J. E., Venturi, M. L. & Shoe, J. L. A molecular timescale of eukaryote evolution and the rise of complex multicellular life. BMC Evol. Biol. 4, 2 (2004).

    PubMed  PubMed Central  Google Scholar 

  98. Blair, J. E., Shah, P. & Hedges, S. B. Evolutionary sequence analysis of complete eukaryote genomes. BMC Bioinformatics 6, 53 (2005).

    PubMed  PubMed Central  Google Scholar 

  99. Thorne, J. L. & Kishino, H. Divergence time and evolutionary rate estimation with multilocus data. Syst. Biol. 51, 689–702 (2002).

    PubMed  Google Scholar 

  100. Sanderson, M. J. r8s: inferring absolute rates of molecular evolution and divergence times in the absence of a molecular clock. Bioinformatics 19, 301–302 (2003).

    CAS  PubMed  Google Scholar 

  101. Benton, M. J. & Ayala, F. J. Dating the tree of life. Science 300, 1698–1700 (2003).

    CAS  PubMed  Google Scholar 

  102. Hedges, S. B. & Kumar, S. Precision of molecular time estimates. Trends Genet. 20, 242–247 (2004).

    CAS  PubMed  Google Scholar 

  103. Glazko, G. V., Koonin, E. V. & Rogozin, I. B. Molecular dating: ape bones agree with chicken entrails. Trends Genet. 21, 89–92 (2005).

    CAS  PubMed  Google Scholar 

  104. Muse, S. V. & Weir, B. S. Testing for equality of evolutionary rates. Genetics 132, 269–276 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Felsenstein, J. Inferring Phylogeny (Sinauer Associates, Sunderland, Massachusetts, 2003).

    Google Scholar 

  106. Li, W. H., Wu, C. I. & Luo, C. C. A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Mol. Biol. Evol. 2, 150–174 (1985).

    PubMed  Google Scholar 

  107. Sharp, P. M. & Li, W. H. On the rate of DNA sequence evolution in Drosophila. J. Mol. Evol. 28, 398–402 (1989).

    CAS  PubMed  Google Scholar 

  108. Chamary, J. V. & Hurst, L. D. Similar rates but different modes of sequence evolution in introns and at exonic silent sites in rodents: evidence for selectively driven codon usage. Mol. Biol. Evol. 21, 1014–1023 (2004).

    CAS  PubMed  Google Scholar 

  109. Kumar, S. & Gadagkar, S. R. Disparity index: a simple statistic to measure and test the homogeneity of substitution patterns between molecular sequences. Genetics 158, 1321–1327 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Waterston, R. H. et al. Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562 (2002).

    CAS  PubMed  Google Scholar 

  111. Herbert, G. & Easteal, S. Relative rates of nuclear DNA evolution in human and Old World monkey lineages. Mol. Biol. Evol. 13, 1054–1057 (1996).

    CAS  PubMed  Google Scholar 

  112. Sarich, V. M. & Wilson, A. C. Immunological time scale for hominid evolution. Science 158, 1200–1203 (1967).

    CAS  PubMed  Google Scholar 

  113. Brown, R. H., Richardson, M., Boulter, D., Ramshaw, J. A. & Jefferies, R. P. The amino acid sequence of cytochrome c from Helix aspersa Muller (garden snail). Biochem. J. 128, 971–974 (1972).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Hori, H. & Osawa, S. Evolutionary change in 5S RNA secondary structure and a phylogenic tree of 54 5S RNA species. Proc. Natl Acad. Sci. USA 76, 381–385 (1979).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Miyata, T., Yasunaga, T. & Nishida, T. Nucleotide sequence divergence and functional constraint in mRNA evolution. Proc. Natl Acad. Sci. USA 77, 7328–7332 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Hasegawa, M., Kishino, H. & Yano, T. Man's place in Hominoidea as inferred from molecular clocks of DNA. J. Mol. Evol. 26, 132–147 (1987).

    CAS  PubMed  Google Scholar 

  117. Rand, D. M. Thermal habit, metabolic rate, and the evolution of mitochondrial DNA. Trends Ecol. Evol. 9, 125–131 (1994).

    CAS  PubMed  Google Scholar 

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Acknowledgements

I thank A. Filipski and S.B. Hedges for their insights and for a critical review of different versions of this manuscript. G. Valente and V. Swarna helped in locating references and compiling data; D. Desonie provided editorial support; and S. Subramanian, C. Kuslich, J.E. Blair and A. Briscoe provided scientific feedback on an earlier draft. This work was supported by a research grant from the US National Institutes of Health.

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Molecular Evolutionary Genetics Analysis (MEGA) software package

Multidivtime divergence-time estimation software

National Center for Biotechnology Information web site

Phylogenetic Analysis by Maximum Likelihood (PAML) software package

Sudhir Kumar's Laboratory

Timescale evolutionary database

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Kumar, S. Molecular clocks: four decades of evolution. Nat Rev Genet 6, 654–662 (2005). https://doi.org/10.1038/nrg1659

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