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The molecular clock (based on the molecular clock hypothesis (MCH)) is a technique in genetics, which researchers use to date when two species diverged. It deduces elapsed time from the number of minor differences between their DNA sequences. It is sometimes called a gene clock.

The notion of a "molecular clock" was first attributed to Emile Zuckerkandl and Linus Pauling who, in 1962, noticed that the quantity of amino acid differences in hemoglobin between lineages roughly matched the known evolutionary rate of divergence based upon fossil evidence. They generalized this observation to assert that the rate of evolutionary change of any specified protein was approximately constant over time and over different lineages. It has been applied to DNA sequence evolution also, particularly neutral evolution.

Later Allan Wilson and Vincent Sarich built upon this work and the work of Motoo Kimura (1968) observed and formalized that rare spontaneous errors in DNA replication cause the mutations that drive molecular evolution, and that the accumulation of evolutionarily "neutral" differences between two sequences could be used to measure time, if the error rate of DNA replication could be calibrated. One method of calibrating the error rate was to use as references pairs of groups of living species whose date of speciation was already known from the fossil record.

Originally, it was assumed that the DNA replication error rate was constant--not just over time, but across all species and every part of a genome that you might want to compare. Because the enzymes that replicate DNA differ only very slightly between species, the assumption seemed reasonable a priori. As molecular evidence has accumulated, the constant-rate assumption has proven false--or at least overly general. However while the MCH cannot be blindly assumed to be true, it does hold in many cases, and these can be tested for.

For example, molecular clock users are developing workaround solutions using a number of statistical approaches including maximum likelihood techniques and later Bayesian modeling. In particular, models that take into account rate variation across lineages have been proposed in order to obtain better estimates of divergence times. These models are called relaxed molecular clocks. It must be remembered that these are still based on statistical inference and not on direct evidence and that therefore, strictly speaking even a relaxed molecular clock can only support but never prove a scientific hypothesis. This problem is approached by using the fossil record, which quite often is good and well-documented enough to provide hard evidence, to calibrate the molecular clock accordingly.

The molecular clock technique is an important tool in molecular systematics, the use of molecular genetics information to determine the correct scientific classification of organisms. Knowledge of approximately-constant rate of molecular evolution in particular sets of lineages also facilitates establishing the dates of phylogenetic events not documented by fossils, such as the divergence of living taxa.

See also


  • Kimura, M. (1968). Evolutionary Rate at the Molecular Level. Nature 217: 624-626. [1]
  • Morgan, G.J. (1998). Emile Zuckerkandl, Linus Pauling, and the Molecular Evolutionary Clock, 1959-1965. Journal of the History of Biology 31: 155-178.
  • Sarich, V.M. and Wilson, A.C. (1967). Immunological time scale for hominid evolution. Science 158: 1200-1203.
  • Zuckerkandl, E., and Pauling, L. (1962). Molecular disease, evolution, and genetic heterogeneity, pp. 189–225 in Horizons in Biochemistry, edited by M. Kasha and B. Pullman. Academic Press, New York.
  • Zuckerkandl, E., and Pauling, L. (1965). Evolutionary divergence and convergence in proteins, pp. 97–166 in Evolving Genes and Proteins, edited by V. Bryson and H. J. Vogel. Academic Press, New York.

External links

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