Dating Methods: Genetic

  • Simon Y. W. HoEmail author
  • Phillip Endicott
Living reference work entry


Human genomes contain the signatures of the evolutionary and demographic processes that shaped them. This includes information about the timescales over which these processes occurred. Using a tool known as the molecular clock, analyses of genetic data can produce estimates of the timing of divergence between species, major migrations in the past, and changes in population sizes. Molecular clocks can even be used to estimate the ages of ancient samples, such as those from ancient modern humans or archaic hominins. Collectively, these date estimates offer a valuable complement to the temporal information provided by archaeology and paleontology.

The molecular clock describes the relationship between genetic change and time. It relies on the fundamental assumption that mutations cause genomes to diverge gradually from each other. In its simplest form, the molecular clock assumes that the rate of genetic change has been constant through time and across populations and...

This is a preview of subscription content, log in to check access.


  1. Anderson, S., A.T. Bankier, B.G. Barrell, M.H.L. de Bruijn, A.R. Coulson, J. Drouin, I.C. Eperon, D.P. Nierlich, B.A. Roe, F. Sanger, P.H. Schreier, A.J.H. Smith, R. Staden, and I.G. Young. 1981. Sequence and organization of the human mitochondrial genome. Nature 290: 457–465.CrossRefGoogle Scholar
  2. Baele, G., W.L.S. Li, A.J. Drummond, M.A. Suchard, and P. Lemey. 2013. Accurate model selection of relaxed molecular clocks in Bayesian phylogenetics. Molecular Biology and Evolution 30: 239–243.CrossRefGoogle Scholar
  3. Benton, M.J., P.C.J. Donoghue, R.A. Asher, M. Friedman, T.J. Near, and J. Vinther. 2015. Constraints on the timescale of animal evolutionary history. Palaeontologia Electronica 18: 18.1.1FC.Google Scholar
  4. Bromham, L. 2009. Why do species vary in their rate of molecular evolution? Biology Letters 5: 401–404.CrossRefGoogle Scholar
  5. Bromham, L., S. Duchêne, X. Hua, A.M. Ritchie, D.A. Duchêne, and S.Y.W. Ho. 2018. Bayesian molecular dating: Opening up the black box. Biological Reviews 93: 1165–1191CrossRefGoogle Scholar
  6. Brotherton, P., W. Haak, J. Templeton, G. Brandt, J. Soubrier, C.J. Adler, S.M. Richards, C. Der Sarkissian, R. Ganslmeier, S. Friederich, V. Dresely, M. van Oven, R. Kenyon, M.B. Van der Hoek, J. Korlach, K. Luong, S.Y.W. Ho, L. Quintana-Murci, D.M. Behar, H. Meller, K.W. Alt, A. Cooper, and The Genographic Consortium. 2013. Neolithic mitochondrial haplogroup H genomes and the genetic origins of Europeans. Nature Communications 4: 1764.CrossRefGoogle Scholar
  7. Campbell, C.D., J.X. Chong, M. Malig, A. Ko, B.L. Dumont, L. Han, L. Vives, B.J. O’Roak, P.H. Sudmant, J. Shendure, M. Abney, C. Ober, and E.E. Eichler. 2012. Estimating the human mutation rate using autozygosity in a founder population. Nature Genetics 44: 1277–1281.CrossRefGoogle Scholar
  8. Doolittle, R.F., D.-F. Feng, S. Tsang, G. Cho, and E. Little. 1996. Determining divergence times of the major kingdoms of living organisms with a protein clock. Science 271: 470–477.CrossRefGoogle Scholar
  9. dos Reis, M., Y. Thawornwattana, K. Angelis, M.J. Telford, P.C.J. Donoghue, and Z. Yang. 2015. Uncertainty in the timing of origin of animals and the limits of precision in molecular timescales. Current Biology 25: 2939–2950.CrossRefGoogle Scholar
  10. dos Reis, M., P.C.J. Donoghue, and Z. Yang. 2016. Bayesian molecular clock dating of species divergences in the genomics era. Nature Reviews Genetics 17: 71–80.CrossRefGoogle Scholar
  11. Drummond, A.J., and M.A. Suchard. 2010. Bayesian random local clocks, or one rate to rule them all. BMC Biology 8: 114.CrossRefGoogle Scholar
  12. Drummond, A.J., S.Y.W. Ho, M.J. Phillips, and A. Rambaut. 2006. Relaxed phylogenetics and dating with confidence. PLoS Biology 4: e88.CrossRefGoogle Scholar
  13. Duchêne, D.A., S. Duchêne, E.C. Holmes, and S.Y.W. Ho. 2015. Evaluating the adequacy of molecular clock models using posterior predictive simulations. Molecular Biology and Evolution 32: 2986–2995.CrossRefGoogle Scholar
  14. Endicott, P., S.Y.W. Ho, M. Metspalu, and C. Stringer. 2009. Evaluating the mitochondrial timescale of human evolution. Trends in Ecology and Evolution 24: 515–521.CrossRefGoogle Scholar
  15. Foster, C.S.P., H. Sauquet, M. Van Der Merwe, H. McPherson, M. Rossetto, and S.Y.W. Ho. 2017. Evaluating the impact of genomic data and priors on Bayesian estimates of the angiosperm evolutionary timescale. Systematic Biology 66: 338–351.Google Scholar
  16. Fu, Q., A. Mittnik, P.L.F. Johnson, K. Bos, M. Lari, R. Bollongino, C. Sun, L. Giemsch, R. Schmitz, J. Burger, A.M. Ronchitelli, F. Martini, R.G. Cremonesi, J. Svoboda, P. Bauer, D. Caramelli, S. Castellano, D. Reich, S. Pääbo, and J. Krause. 2013. A revised timescale for human evolution based on ancient mitochondrial genomes. Current Biology 23: 553–559.CrossRefGoogle Scholar
  17. Fu, Q., H. Li, P. Moorjani, F. Jay, S.M. Slepchenko, A.A. Bondarev, P.L.F. Johnson, A. Aximu-Petri, K. Prüfer, C. de Filippo, M. Meyer, N. Zwyns, D.C. Salazar-García, Y.V. Kuzmin, S.G. Keates, P.A. Kosintsev, D.I. Razhev, M.P. Richards, N.V. Peristov, M. Lachmann, K. Douka, T.F.G. Higham, M. Slatkin, J.-J. Hublin, D. Reich, J. Kelso, T.B. Viola, and S. Pääbo. 2014. Genome sequence of a 45,000-year-old modern human from western Siberia. Nature 514: 445–449.CrossRefGoogle Scholar
  18. Gignoux, C.R., B.M. Henn, and J.L. Mountain. 2011. Rapid, global demographic expansions after the origins of agriculture. Proceedings of the National Academy of Sciences of the United States of America 108: 6044–6049.CrossRefGoogle Scholar
  19. Gillespie, J.H. 1991. The causes of molecular evolution. Oxford: Oxford University Press.Google Scholar
  20. Helgason, A., A.W. Einarsson, V.B. Gudmundsdóttir, A.M. Sigurdsson, E.D. Gunnarsdóttir, A. Jagadeesan, S.S. Ebenesersdóttir, A. Kong, and K. Stefánsson. 2015. The Y-chromosome point mutation rate in humans. Nature Genetics 47: 453–457.CrossRefGoogle Scholar
  21. Henn, B.M., C.R. Gignoux, M.W. Feldman, and J.L. Mountain. 2008. Characterizing the time dependency of human mitochondrial DNA mutation rate estimates. Molecular Biology and Evolution 26: 217–230.CrossRefGoogle Scholar
  22. Ho, S.Y.W. 2014. The changing face of the molecular evolutionary clock. Trends in Ecology and Evolution 29: 496–503.CrossRefGoogle Scholar
  23. Ho, S.Y.W., and S. Duchêne. 2014. Molecular-clock methods for estimating evolutionary rates and timescales. Molecular Ecology 23: 5947–5965.CrossRefGoogle Scholar
  24. Howell, N., C.B. Smejkal, D.A. Mackey, P.F. Chinnery, D.M. Turnbull, and C. Herrnstadt. 2003. The pedigree rate of sequence divergence in the human mitochondrial genome: There is a difference between phylogenetic and pedigree rates. American Journal of Human Genetics 72: 659–670.CrossRefGoogle Scholar
  25. Karmin, M., L. Saag, M. Vicente, M.A. Wilson Sayres, M. Järve, U.G. Talas, S. Rootsi, A.M. Ilumäe, R. Mägi, M. Mitt, L. Pagani, T. Puurand, Z. Faltyskova, F. Clemente, A. Cardona, E. Metspalu, H. Sahakyan, B. Yunusbayev, G. Hudjashov, M. DeGiorgio, E.L. Loogväli, C. Eichstaedt, M. Eelmets, G. Chaubey, K. Tambets, S. Litvinov, M. Mormina, Y. Xue, Q. Ayub, G. Zoraqi, T.S. Korneliussen, F. Akhatova, J. Lachance, S. Tishkoff, K. Momynaliev, F.-X. Ricaut, P. Kusuma, H. Razafindrazaka, D. Pierron, M.P. Cox, G.N.N. Sultana, R. Willerslev, C. Muller, M. Westaway, D. Lambert, V. Skaro, L. Kovacevic, S. Turdikulova, D. Dalimova, R. Khusainova, N. Trofimova, V. Akhmetova, I. Khidiyatova, D.V. Lichman, J. Isakova, E. Pocheshkhova, Z. Sabitov, N.A. Barashkov, P. Nymadawa, E. Mihailov, J.W.T. Seng, I. Evseeva, A.B.. Migliano, S. Abdullah, G. Andriadze, D. Primorac, L. Atramentova, O. Utevska, L. Yepiskoposyan, D. Marjanovic, A. Kushniarevich, D.M. Behar, C. Gilissen, L. Vissers, J.A. Veltman, E. Balanovska, M. Derenko, B. Malyarchuk, A. Metspalu, S. Fedorova, A. Eriksson, A. Manica, F.L. Mendez, T.M. Karafet, K.R. Veeramah, N. Bradman, M.F. Hammer, L.P. Osipova, O. Balanovsky, E.K. Khusnutdinova, K. Johnsen, M. Remm, M.G. Thomas, C. Tyler-Smith, P.A. Underhill, E. Willerslev, R. Nielsen, M. Metspalu, R. Villems, and T. Kivisild. 2015. A recent bottleneck of Y chromosome diversity coincides with a global change in culture. Genome Research 25: 459–466.CrossRefGoogle Scholar
  26. Langley, C.H., and W.M. Fitch. 1974. An examination of the constancy of the rate of molecular evolution. Journal of Molecular Evolution 3: 161–177.CrossRefGoogle Scholar
  27. Marciniak, S., and G.H. Perry. 2017. Harnessing ancient genomes to study the history of human adaptation. Nature Reviews Genetics 18: 659–674.CrossRefGoogle Scholar
  28. Meyer, M., J.-L. Arsuaga, C. de Filippo, S. Nagel, A. Aximu-Petri, B. Nickel, I. Martínez, A. Gracia, J.M. Bermúdez de Castro, E. Carboneil, B. Viola, J. Kelso, K. Prüfer, and S. Pääbo. 2016. Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins. Nature 531: 504–507.CrossRefGoogle Scholar
  29. Moorjani, P., S. Sankararaman, Q. Fu, M. Przeworksi, N. Patterson, and D. Reich. 2016a. A genetic method for dating ancient genomes provides a direct estimate of human generation interval in the last 45,000 years. Proceedings of the National Academy of Sciences of the United States of America 113: 5652–5657.CrossRefGoogle Scholar
  30. Moorjani, P., C.E.G. Amorim, P.F. Arndt, and M. Przeworksi. 2016b. Variation in the molecular clock of primates. Proceedings of the National Academy of Sciences of the United States of America 113: 10607–10612.CrossRefGoogle Scholar
  31. Nielsen, R., and M.A. Beaumont. 2009. Statistical inferences in phylogeography. Molecular Ecology 18: 1034–1047.CrossRefGoogle Scholar
  32. Nielsen, R., J.M. Akey, M. Jakobssen, J.K. Pritchard, S. Tishkoff, and E. Willerslev. 2017. Tracing the peopling of the world through genomics. Nature 541: 302–310.CrossRefGoogle Scholar
  33. Palamara, P.F., L.C. Francioli, P.R. Wilton, G. Genovese, A. Gusev, H.K. Finucane, S. Sankararaman, Genome of the Netherlands Consortium, S.R. Sunyaev, P.I.W. de Bakker, J. Wakeley, I. Pe’er, and A.L. Price. 2015. Leveraging distant relatedness to quantify human mutation rate and gene-conversion rates. American Journal of Human Genetics 97: 775–789.Google Scholar
  34. Prüfer, K., F. Racimo, N. Patterson, F. Jay, S. Sankararaman, S. Sawyer, A. Heinze, G. Renaud, P.H. Sudmant, C. de Filippo, H. Li, S. Mallick, M. Dannemann, Q. Fu, M. Kircher, M. Kuhlwilm, M. Lachmann, M. Meyer, M. Ongyerth, M. Siebauer, C. Theunert, A. Tandon, P. Moorjani, J. Pickrell, J.C. Mullikin, S.H. Vohr, R.E. Green, I. Hellmann, P.L.F. Johnson, H. Blanche, H. Cann, J.O. Kitzman, J. Shendure, E.E. Eichler, E.S. Lein, T.E. Bakken, L.V. Golovanova, V.B. Doronichev, M.V. Shunkov, A.P. Derevianko, B. Viola, M. Slatkin, D. Reich, J. Kelso, and S. Pääbo. 2014. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505: 43–49.CrossRefGoogle Scholar
  35. Rieux, A., and F. Balloux. 2016. Inferences from tip-calibrated phylogenies: A review and a practical guide. Molecular Ecology 25: 1911–1924.CrossRefGoogle Scholar
  36. Rieux, A., A. Eriksson, M. Li, B. Sobkowiak, L.A. Weinert, V. Warmuth, A. Ruiz-Linares, A. Manica, and F. Balloux. 2014. Improved calibration of the human mitochondrial clock using ancient genomes. Molecular Biology and Evolution 31: 2780–2792.CrossRefGoogle Scholar
  37. Sanderson, M.J. 1997. A nonparametric approach to estimating divergence times in the absence of rate constancy. Molecular Biology and Evolution 14: 1218–1231.CrossRefGoogle Scholar
  38. Sarich, V.M., and A.C. Wilson. 1967. Immunological time scale for hominid evolution. Science 158: 1200–1203.CrossRefGoogle Scholar
  39. Scally, A. 2016. The mutation rate in human evolution and demographic inference. Current Opinion in Genetics and Development 41: 36–43.CrossRefGoogle Scholar
  40. Scally, A., and R. Durbin. 2012. Revising the human mutation rate: Implications for understanding human evolution. Nature Reviews Genetics 13: 745–753.CrossRefGoogle Scholar
  41. Shapiro, B., S.Y.W. Ho, A.J. Drummond, M.A. Suchard, O.G. Pybus, and A. Rambaut. 2011. A Bayesian phylogenetic method to estimate unknown sequence ages. Molecular Biology and Evolution 28: 879–887.CrossRefGoogle Scholar
  42. Thorne, J.L., H. Kishino, and I.S. Painter. 1998. Estimating the rate of evolution of the rate of molecular evolution. Molecular Biology and Evolution 15: 1647–1657.CrossRefGoogle Scholar
  43. To, T.-H., M. Jung, S. Lycett, and O. Gascuel. 2016. Fast dating using least-squares criteria and algorithms. Systematic Biology 65: 82–97.CrossRefGoogle Scholar
  44. Venn, O., I. Turner, I. Mathieson, N. de Groot, R. Bontrop, and G. McVean. 2014. Strong male bias drives germline mutation in chimpanzees. Science 344: 1272–1275.CrossRefGoogle Scholar
  45. Willems, T., M. Gymrek, G.D. Poznik, C. Tyler-Smith, The 1000 Genomes Project Chromosome Y Group, and Y. Erlich. 2016. Population-scale sequencing data enable precise estimates of Y-STR mutation rates. American Journal of Human Genetics 98: 919–933.CrossRefGoogle Scholar
  46. Wong, W.S.W., B.D. Solomon, D.L. Bodian, P. Kothiyal, G. Eley, K.C. Huddleston, R. Baker, D.C. Thach, R.K. Iyer, J.G. Vockley, and J.E. Niederhuber. 2016. New observations on maternal age effect on germline de novo mutations. Nature Communications 7: 10486.CrossRefGoogle Scholar
  47. Yang, Z., and B. Rannala. 2012. Molecular phylogenetics: Principles and practice. Nature Reviews Genetics 13: 303–314.CrossRefGoogle Scholar
  48. Yoder, A.D., and Z. Yang. 2000. Estimation of primate speciation dates using local molecular clocks. Molecular Biology and Evolution 17: 1081–1090.CrossRefGoogle Scholar
  49. Zuckerkandl, E., and L. Pauling. 1962. Molecular disease, evolution and genic heterogeneity. In Horizons in biochemistry, ed. M. Kasha and B. Pullman, 189–225. New York: Academic Press.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.School of Life and Environmental SciencesUniversity of SydneySydneyAustralia
  2. 2.Départment Hommes Natures SociétésMusée de l’HommeParisFrance

Section editors and affiliations

  • Chen Shen
    • 1
  1. 1.Department of World CulturesRoyal Ontario MuseumTorontoCanada