Molecular clock

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The molecular clock is a metaphor for a method in genetics that uses DNA sequencing to estimate when two species split from a common ancestor. The more mutations (differences in the DNA sequence) that have arisen after the split, the longer the development time ( evolution time) has been since then. It is difficult to determine the mutation rate (the frequency of mutations) and thus to calibrate the “speed” of the molecular clock .

The molecular clock technique is an important tool in molecular genetics for dating evolutionary events and for classifying living things .

Research and calibration

The term molecular clock was introduced by Emile Zuckerkandl and Linus Pauling . In 1962 they noticed that the amino acids in hemoglobin became more and more different the longer the separate evolutionary periods of two species . They generalized their observation to the hypothesis that the mutation rate of any protein is constant over time during evolution.

In 1967 Allan Wilson and Vincent Sarich applied this hypothesis in particular to the evolution of the hominini ( humans and their immediate fossil ancestors). Their timescale was shifted significantly to the older one in a recalculation in 2012, especially for the development of Homo sapiens .

A temporarily increased selection pressure can, however, mean that mutations prevail more quickly in a population and thus - with a constant mutation rate - the rate of the molecular clock accelerates. Motoo Kimura observed in 1968 that although many mutations change the DNA sequences, they do not affect the phenotype ( neutral theory ) and are therefore not subject to selection . These evolutionarily “neutral” differences can be used to measure time. For calibration, species were used as reference for which the time of their splitting was known from fossil finds.

In 1999 Francisco J. Ayala listed five factors that influence the speed of the molecular clock:

  • Generation duration (the shorter the generation duration, the faster mutations are fixed)
  • Population size (the larger the population, the more mutations are selected)
  • species-specific differences
  • Function of a protein
  • Change of natural selection (change of readout conditions)

According to Ayala, researchers come up with very different results, depending on the organisms and genes used. The various molecular clocks were too imprecise despite more precise analysis and better data. The clock speeds are still not understood.


  • The emergence of the human immunodeficiency virus ( HIV ): The virus type HIV-1 spread to humans in the early 20th century, HIV-2 only in the 1930s.


  • Emile Zuckerkandl, Linus Pauling: Molecular disease, evolution, and genetic heterogeneity . In: Albert Szent-Györgyi: Horizons in Biochemistry. Academic Press, New York 1962.
  • Emile Zuckerkandl, Linus Pauling: Evolutionary divergence and convergence in proteins . In: HV Bryson: Evolving Genes and Proteins. Academic Press, New York 1965, pp. 97-166.
  • Motoo Kimura: Evolutionary Rate at the Molecular Level . In: Nature . Volume 217, 1968, pp. 624-626, doi: 10.1038 / 217624a0 , full text (PDF) . ISSN  0028-0836
  • Francisco J. Ayala: Vagaries of the molecular clock . In: PNAS . Volume 94, No. 15, 1997, pp. 7776-7783, doi: 10.1073 / pnas.94.15.7776 . ISSN  0027-8424
  • Francisco J. Ayala: Molecular clock mirages . In: Bioessays. Hoboken NJ 21.1999, pp. 71-75. ISSN  0265-9247
  • Emmanuel JP Douzery, Frédéric Delsuc, Michael J. Stanhope and Dorothée Huchon: Local molecular clocks in three nuclear genes: divergence times for rodents and other mammals, and incompatibility among fossil calibrations . In: Journal of molecular evolution. Volume 57, Supplement 1, 2003, pp. S201-S213, doi: 10.1007 / s00239-003-0028-x . ISSN  0022-2844

Web links

Individual evidence

  1. Vincent M. Sarich, Allan C. Wilson: Immunological time scale for hominid evolution . In: Science . 158. New York 1967, pp. 1200-1203. doi: 10.1126 / science.158.3805.1200 ISSN  0036-8075
  2. Aylwyn Scally, Richard Durbin: Revising the human mutation rate: implications for understanding human evolution. In: Nature Reviews Genetics. Volume 13, 2012, pp. 745-753, doi: 10.1038 / nrg3295
  3. ^ Ewen Callaway: Studies slow the human DNA clock. In: Nature. Volume 489, No. 7416, 2012, pp. 343-344 doi: 10.1038 / 489343a
  4. The history of the HI virus. On: from July 27, 2008