Molecular Clocks


The molecular clock hypothesis postulates that the rate of evolution in a macromolecule is approximately constant per year over time and among different evolutionary lineages. While local clocks in closely related organisms with similar generation times can be useful for dating evolutionary events, strong evidence now suggests that no global or universal clock exists in mammals.

Keywords: molecular clock; relative‐rate test; generation‐time effect hypothesis; hominoid‐slowdown hypothesis; mutation rate; unequal rates

Figure 1.

The rooted tree for species A, B and C, assuming that C is the known outgroup. O denotes the common ancestor of species A and B.



Ayala FJ (1999) Molecular clock mirages. BioEssays 21: 71–75.

Bromham L, Penny D, Rambaut A and Hendy MD (2000) The power of relative rates tests depends on the data. Journal of Molecular Evolution 50: 296–301.

Brunet M, Guy F, Pilbeam D et al. (2002) A new hominid from the upper Miocene of Chad, Central Africa. Nature 418: 145–151.

Cutler DJ (2000) Estimating divergence times in the presence of an overdispersed molecular clock. Molecular Biology and Evolution 17: 1647–1660.

Delson E (2000) Encyclopedia of Human Evolution and Prehistory. New York, NY: Garland.

Goodman M (1961) The role of immunochemical differences in the phyletic development of human behavior. Human Biology 33: 131–162.

Goodman M, Barnabas J, Matsuda G and Moore GW (1971) Molecular evolution in the descent of man. Nature 233: 604–613.

Huelsenbeck JP, Larget B and Swofford D (2000) A compound Poisson process for relaxing the molecular clock. Genetics 154: 1879–1892.

Kohne DE (1970) Evolution of higher‐organism DNA. Quarterly Reviews in Biophysics 33: 1–48.

Koop BF, Goodman M, Xu P, Chan K and Slightom JL (1986) Primate η‐globin DNA sequences and man's place among the great apes. Nature 319: 234–238.

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

Kumar S and Subramanian S (2002) Mutation rates in mammalian genomes. Proceedings of the National Academy of Sciences of the United States of America 99: 803–808.

Laird CD, McConaughy BL and McCarthy BJ (1969) Rate of fixation of nucleotide substitutions in evolution. Nature 224: 149–154.

Li P and Bousquet J (1992) Relative‐rate test for nucleotide substitutions between two lineages. Molecular Biology and Evolution 9: 1185–1189.

Li WH (1997) Molecular Evolution. Sunderland, MA: Sinauer.

Li WH and Tanimura M (1987) The molecular clock runs more slowly in man than in apes and monkeys. Nature 326: 93–96.

Mouchiroud D, Robinson M and Gautier C (1997) Impact of changes in GC content on the silent molecular clock in murids. Gene 205: 317–322.

Muse SV and Weir BS (1992) Testing for equality of evolutionary rates. Genetics 132: 269–276.

Nuttall GHF (1904) Blood Immunity and Blood Relationship. Cambridge, UK: Cambridge University Press.

O'hUigin C and Li WH (1992) The molecular clock ticks regularly in muroid rodents and hamsters. Journal of Molecular Evolution 35: 377–384.

Rodriguez‐Trelles F, Tarrio R and Ayala FJ (2001) Erratic overdispersion of three molecular clocks: GPDH, SOD, and XDH. Proceedings of the National Academy of Sciences of the United States of America 98: 11405–11410.

Sarich VM and Wilson AC (1973) Generation time and genomic evolution in primates. Science 179: 1144–1147.

Tourasse NJ and Li WH (1999) Performance of the relative‐rate test under nonstationary models of nucleotide substitution. Molecular Biology and Evolution 16: 1068–1078.

Wilson AC, Carlson SS and White TJ (1977) Biochemical evolution. Annual Reviews in Biochemistry 46: 573–639.

Wu CI and Li WH (1985) Evidence for higher rates of nucleotide substitution in rodents than in man. Proceedings of the National Academy of Sciences of the United States of America 82: 1741–1745.

Yang Z (1999) Phylogenetic analysis by maximum likelihood (PAML). London, UK: University College London.

Yang Z and Nielsen R (1998) Synonymous and nonsynonymous rate variation in nuclear genes of mammals. Journal of Molecular Evolution 46: 409–418.

Yi S, Ellsworth DL and Li WH (2002) Slow molecular clocks in Old World monkeys, apes and humans. Molecular Biology and Evolution 19: 2191–2198.

Zuckerkandl E and Pauling L (1965) Evolutionary divergence and convergence in proteins. In: Bryson V and Vogel HJ (eds.) Evolving Genes and Proteins, pp. 97–166. New York, NY: Academic Press.

Further Reading

Ho SY and Larson G (2006) Molecular clocks: when times are a‐changin. Trends in Genetics 22: 79–83.

Kumar S (2005) Molecular clocks: four decades of evolution. Nature Reviews Genetics 6: 654–662.

Web Links

Phylogenetic analysis by maximum likelihood (PAML). Free download site

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How to Cite close
Li, Wen‐Hsiung, and Makova, Kateryna D(Apr 2008) Molecular Clocks. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005111.pub2]