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. 1993 Dec;135(4):1197–1208. doi: 10.1093/genetics/135.4.1197

A Method for Calibrating Molecular Clocks and Its Application to Animal Mitochondrial DNA

M Lynch 1, P E Jarrell 1
PMCID: PMC1205750  PMID: 7508408

Abstract

A generalized least-squares procedure is introduced for the calibration of molecular clocks and applied to the complete mitochondrial DNA sequences of 13 animal species. The proposed technique accounts for both nonindependence and heteroscedasticity of molecular-distance data, problems that have not been taken into to account in such analyses in the past. When sequence-identity data are transformed to account for multiple substitutions/site, the molecular divergence scales linearly with time, but with substantially more variation in the substitution rate than expected under a Poisson model. Significant levels of divergence are predicted at zero divergence time for most loci, suggesting high levels of site-specific heterozygosity among mtDNA molecules establishing in sister taxa. For nearly all loci, the baseline heterozygosity is lower and the substitution rate is higher in mammals relative to other animals. There is considerable variation in the evolutionary rate among loci but no compelling evidence that the average rate of mtDNA evolution is elevated with respect to that of nuclear DNA. Using the observed patterns of interspecific divergence, empirical estimates are derived for the mean coalescence times of organelles colonizing sister taxa.

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Selected References

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  1. Anderson S., Bankier A. T., Barrell B. G., de Bruijn M. H., Coulson A. R., Drouin J., Eperon I. C., Nierlich D. P., Roe B. A., Sanger F. Sequence and organization of the human mitochondrial genome. Nature. 1981 Apr 9;290(5806):457–465. doi: 10.1038/290457a0. [DOI] [PubMed] [Google Scholar]
  2. Anderson S., de Bruijn M. H., Coulson A. R., Eperon I. C., Sanger F., Young I. G. Complete sequence of bovine mitochondrial DNA. Conserved features of the mammalian mitochondrial genome. J Mol Biol. 1982 Apr 25;156(4):683–717. doi: 10.1016/0022-2836(82)90137-1. [DOI] [PubMed] [Google Scholar]
  3. Arnason U., Gullberg A., Widegren B. The complete nucleotide sequence of the mitochondrial DNA of the fin whale, Balaenoptera physalus. J Mol Evol. 1991 Dec;33(6):556–568. doi: 10.1007/BF02102808. [DOI] [PubMed] [Google Scholar]
  4. Arnason U., Johnsson E. The complete mitochondrial DNA sequence of the harbor seal, Phoca vitulina. J Mol Evol. 1992 Jun;34(6):493–505. doi: 10.1007/BF00160463. [DOI] [PubMed] [Google Scholar]
  5. Beverley S. M., Wilson A. C. Molecular evolution in Drosophila and the higher Diptera II. A time scale for fly evolution. J Mol Evol. 1984;21(1):1–13. doi: 10.1007/BF02100622. [DOI] [PubMed] [Google Scholar]
  6. Bibb M. J., Van Etten R. A., Wright C. T., Walberg M. W., Clayton D. A. Sequence and gene organization of mouse mitochondrial DNA. Cell. 1981 Oct;26(2 Pt 2):167–180. doi: 10.1016/0092-8674(81)90300-7. [DOI] [PubMed] [Google Scholar]
  7. Brown W. M., George M., Jr, Wilson A. C. Rapid evolution of animal mitochondrial DNA. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1967–1971. doi: 10.1073/pnas.76.4.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brown W. M., Prager E. M., Wang A., Wilson A. C. Mitochondrial DNA sequences of primates: tempo and mode of evolution. J Mol Evol. 1982;18(4):225–239. doi: 10.1007/BF01734101. [DOI] [PubMed] [Google Scholar]
  9. Bulmer M. Estimating the variability of substitution rates. Genetics. 1989 Nov;123(3):615–619. doi: 10.1093/genetics/123.3.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bulmer M., Wolfe K. H., Sharp P. M. Synonymous nucleotide substitution rates in mammalian genes: implications for the molecular clock and the relationship of mammalian orders. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):5974–5978. doi: 10.1073/pnas.88.14.5974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cantatore P., Roberti M., Rainaldi G., Gadaleta M. N., Saccone C. The complete nucleotide sequence, gene organization, and genetic code of the mitochondrial genome of Paracentrotus lividus. J Biol Chem. 1989 Jul 5;264(19):10965–10975. [PubMed] [Google Scholar]
  12. Clary D. O., Wolstenholme D. R. The mitochondrial DNA molecular of Drosophila yakuba: nucleotide sequence, gene organization, and genetic code. J Mol Evol. 1985;22(3):252–271. doi: 10.1007/BF02099755. [DOI] [PubMed] [Google Scholar]
  13. Desjardins P., Morais R. Sequence and gene organization of the chicken mitochondrial genome. A novel gene order in higher vertebrates. J Mol Biol. 1990 Apr 20;212(4):599–634. doi: 10.1016/0022-2836(90)90225-B. [DOI] [PubMed] [Google Scholar]
  14. Easteal S. The pattern of mammalian evolution and the relative rate of molecular evolution. Genetics. 1990 Jan;124(1):165–173. doi: 10.1093/genetics/124.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gadaleta G., Pepe G., De Candia G., Quagliariello C., Sbisà E., Saccone C. The complete nucleotide sequence of the Rattus norvegicus mitochondrial genome: cryptic signals revealed by comparative analysis between vertebrates. J Mol Evol. 1989 Jun;28(6):497–516. doi: 10.1007/BF02602930. [DOI] [PubMed] [Google Scholar]
  16. Gillespie J. H. The molecular clock may be an episodic clock. Proc Natl Acad Sci U S A. 1984 Dec;81(24):8009–8013. doi: 10.1073/pnas.81.24.8009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gyllensten U., Wharton D., Josefsson A., Wilson A. C. Paternal inheritance of mitochondrial DNA in mice. Nature. 1991 Jul 18;352(6332):255–257. doi: 10.1038/352255a0. [DOI] [PubMed] [Google Scholar]
  18. Hasegawa M., Kishino H. Heterogeneity of tempo and mode of mitochondrial DNA evolution among mammalian orders. Jpn J Genet. 1989 Aug;64(4):243–258. doi: 10.1266/jjg.64.243. [DOI] [PubMed] [Google Scholar]
  19. Hoeh W. R., Blakley K. H., Brown W. M. Heteroplasmy suggests limited biparental inheritance of Mytilus mitochondrial DNA. Science. 1991 Mar 22;251(5000):1488–1490. doi: 10.1126/science.1672472. [DOI] [PubMed] [Google Scholar]
  20. Jacobs H. T., Elliott D. J., Math V. B., Farquharson A. Nucleotide sequence and gene organization of sea urchin mitochondrial DNA. J Mol Biol. 1988 Jul 20;202(2):185–217. doi: 10.1016/0022-2836(88)90452-4. [DOI] [PubMed] [Google Scholar]
  21. Lewontin R. C. Inferring the number of evolutionary events from DNA coding sequence differences. Mol Biol Evol. 1989 Jan;6(1):15–32. doi: 10.1093/oxfordjournals.molbev.a040532. [DOI] [PubMed] [Google Scholar]
  22. Li W. H., Tanimura M., Sharp P. M. An evaluation of the molecular clock hypothesis using mammalian DNA sequences. J Mol Evol. 1987;25(4):330–342. doi: 10.1007/BF02603118. [DOI] [PubMed] [Google Scholar]
  23. Liu H., Beckenbach A. T. Evolution of the mitochondrial cytochrome oxidase II gene among 10 orders of insects. Mol Phylogenet Evol. 1992 Mar;1(1):41–52. doi: 10.1016/1055-7903(92)90034-e. [DOI] [PubMed] [Google Scholar]
  24. Lynch M., Crease T. J. The analysis of population survey data on DNA sequence variation. Mol Biol Evol. 1990 Jul;7(4):377–394. doi: 10.1093/oxfordjournals.molbev.a040607. [DOI] [PubMed] [Google Scholar]
  25. Martin A. P., Naylor G. J., Palumbi S. R. Rates of mitochondrial DNA evolution in sharks are slow compared with mammals. Nature. 1992 May 14;357(6374):153–155. doi: 10.1038/357153a0. [DOI] [PubMed] [Google Scholar]
  26. Nei M., Jin L. Variances of the average numbers of nucleotide substitutions within and between populations. Mol Biol Evol. 1989 May;6(3):290–300. doi: 10.1093/oxfordjournals.molbev.a040547. [DOI] [PubMed] [Google Scholar]
  27. Novacek M. J. Mammalian phylogeny: shaking the tree. Nature. 1992 Mar 12;356(6365):121–125. doi: 10.1038/356121a0. [DOI] [PubMed] [Google Scholar]
  28. Roe B. A., Ma D. P., Wilson R. K., Wong J. F. The complete nucleotide sequence of the Xenopus laevis mitochondrial genome. J Biol Chem. 1985 Aug 15;260(17):9759–9774. [PubMed] [Google Scholar]
  29. Sharp P. M., Li W. H. On the rate of DNA sequence evolution in Drosophila. J Mol Evol. 1989 May;28(5):398–402. doi: 10.1007/BF02603075. [DOI] [PubMed] [Google Scholar]
  30. Vawter L., Brown W. M. Nuclear and mitochondrial DNA comparisons reveal extreme rate variation in the molecular clock. Science. 1986 Oct 10;234(4773):194–196. doi: 10.1126/science.3018931. [DOI] [PubMed] [Google Scholar]
  31. Wayne R. K., Van Valkenburgh B., O'Brien S. J. Molecular distance and divergence time in carnivores and primates. Mol Biol Evol. 1991 May;8(3):297–319. doi: 10.1093/oxfordjournals.molbev.a040651. [DOI] [PubMed] [Google Scholar]
  32. Whittam T. S., Clark A. G., Stoneking M., Cann R. L., Wilson A. C. Allelic variation in human mitochondrial genes based on patterns of restriction site polymorphism. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9611–9615. doi: 10.1073/pnas.83.24.9611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wu C. I., Li W. H. Evidence for higher rates of nucleotide substitution in rodents than in man. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1741–1745. doi: 10.1073/pnas.82.6.1741. [DOI] [PMC free article] [PubMed] [Google Scholar]

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