Dynamics of microsatellite divergence under stepwise mutation and proportional slippage/point mutation models (original) (raw)

Abstract

Recently Kruglyak, Durrett, Schug, and Aquadro showed that microsatellite equilibrium distributions can result from a balance between polymerase slippage and point mutations. Here, we introduce an elaboration of their model that keeps track of all parts of a perfect repeat and a simplification that ignores point mutations. We develop a detailed mathematical theory for these models that exhibits properties of microsatellite distributions, such as positive skewness of allele lengths, that are consistent with data but are inconsistent with the predictions of the stepwise mutation model. We use our theoretical results to analyze the successes and failures of the genetic distances (delta(mu))(2) and D(SW) when used to date four divergences: African vs. non-African human populations, humans vs. chimpanzees, Drosophila melanogaster vs. D. simulans, and sheep vs. cattle. The influence of point mutations explains some of the problems with the last two examples, as does the fact that these genetic distances have large stochastic variance. However, we find that these two features are not enough to explain the problems of dating the human-chimpanzee split. One possible explanation of this phenomenon is that long microsatellites have a mutational bias that favors contractions over expansions.

Full Text

The Full Text of this article is available as a PDF (160.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bowcock A. M., Ruiz-Linares A., Tomfohrde J., Minch E., Kidd J. R., Cavalli-Sforza L. L. High resolution of human evolutionary trees with polymorphic microsatellites. Nature. 1994 Mar 31;368(6470):455–457. doi: 10.1038/368455a0. [DOI] [PubMed] [Google Scholar]
  2. Brinkmann B., Klintschar M., Neuhuber F., Hühne J., Rolf B. Mutation rate in human microsatellites: influence of the structure and length of the tandem repeat. Am J Hum Genet. 1998 Jun;62(6):1408–1415. doi: 10.1086/301869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Deka R., Shriver M. D., Yu L. M., Jin L., Aston C. E., Chakraborty R., Ferrell R. E. Conservation of human chromosome 13 polymorphic microsatellite (CA)n repeats in chimpanzees. Genomics. 1994 Jul 1;22(1):226–230. doi: 10.1006/geno.1994.1369. [DOI] [PubMed] [Google Scholar]
  4. Drake J. W., Charlesworth B., Charlesworth D., Crow J. F. Rates of spontaneous mutation. Genetics. 1998 Apr;148(4):1667–1686. doi: 10.1093/genetics/148.4.1667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ellegren H. Heterogeneous mutation processes in human microsatellite DNA sequences. Nat Genet. 2000 Apr;24(4):400–402. doi: 10.1038/74249. [DOI] [PubMed] [Google Scholar]
  6. Ellegren H., Moore S., Robinson N., Byrne K., Ward W., Sheldon B. C. Microsatellite evolution--a reciprocal study of repeat lengths at homologous loci in cattle and sheep. Mol Biol Evol. 1997 Aug;14(8):854–860. doi: 10.1093/oxfordjournals.molbev.a025826. [DOI] [PubMed] [Google Scholar]
  7. Ellegren H. Mutation rates at porcine microsatellite loci. Mamm Genome. 1995 May;6(5):376–377. doi: 10.1007/BF00364807. [DOI] [PubMed] [Google Scholar]
  8. Farrall M., Weeks D. E. Mutational mechanisms for generating microsatellite allele-frequency distributions: an analysis of 4,558 markers. Am J Hum Genet. 1998 May;62(5):1260–1262. doi: 10.1086/301829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Feldman M. W., Bergman A., Pollock D. D., Goldstein D. B. Microsatellite genetic distances with range constraints: analytic description and problems of estimation. Genetics. 1997 Jan;145(1):207–216. doi: 10.1093/genetics/145.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Field D., Wills C. Abundant microsatellite polymorphism in Saccharomyces cerevisiae, and the different distributions of microsatellites in eight prokaryotes and S. cerevisiae, result from strong mutation pressures and a variety of selective forces. Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1647–1652. doi: 10.1073/pnas.95.4.1647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Garza J. C., Slatkin M., Freimer N. B. Microsatellite allele frequencies in humans and chimpanzees, with implications for constraints on allele size. Mol Biol Evol. 1995 Jul;12(4):594–603. doi: 10.1093/oxfordjournals.molbev.a040239. [DOI] [PubMed] [Google Scholar]
  12. Goldstein D. B., Clark A. G. Microsatellite variation in North American populations of Drosophila melanogaster. Nucleic Acids Res. 1995 Oct 11;23(19):3882–3886. doi: 10.1093/nar/23.19.3882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goldstein D. B., Pollock D. D. Launching microsatellites: a review of mutation processes and methods of phylogenetic interference. J Hered. 1997 Sep-Oct;88(5):335–342. doi: 10.1093/oxfordjournals.jhered.a023114. [DOI] [PubMed] [Google Scholar]
  14. Goldstein D. B., Roemer G. W., Smith D. A., Reich D. E., Bergman A., Wayne R. K. The use of microsatellite variation to infer population structure and demographic history in a natural model system. Genetics. 1999 Feb;151(2):797–801. doi: 10.1093/genetics/151.2.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goldstein D. B., Ruiz Linares A., Cavalli-Sforza L. L., Feldman M. W. An evaluation of genetic distances for use with microsatellite loci. Genetics. 1995 Jan;139(1):463–471. doi: 10.1093/genetics/139.1.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Goldstein D. B., Ruiz Linares A., Cavalli-Sforza L. L., Feldman M. W. Genetic absolute dating based on microsatellites and the origin of modern humans. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6723–6727. doi: 10.1073/pnas.92.15.6723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gonser R., Donnelly P., Nicholson G., Di Rienzo A. Microsatellite mutations and inferences about human demography. Genetics. 2000 Apr;154(4):1793–1807. doi: 10.1093/genetics/154.4.1793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Goodman M., Porter C. A., Czelusniak J., Page S. L., Schneider H., Shoshani J., Gunnell G., Groves C. P. Toward a phylogenetic classification of Primates based on DNA evidence complemented by fossil evidence. Mol Phylogenet Evol. 1998 Jun;9(3):585–598. doi: 10.1006/mpev.1998.0495. [DOI] [PubMed] [Google Scholar]
  19. Harr B., Schlötterer C. Long microsatellite alleles in Drosophila melanogaster have a downward mutation bias and short persistence times, which cause their genome-wide underrepresentation. Genetics. 2000 Jul;155(3):1213–1220. doi: 10.1093/genetics/155.3.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Harr B., Weiss S., David J. R., Brem G., Schlötterer C. A microsatellite-based multilocus phylogeny of the Drosophila melanogaster species complex. Curr Biol. 1998 Oct 22;8(21):1183–1186. doi: 10.1016/s0960-9822(07)00490-3. [DOI] [PubMed] [Google Scholar]
  21. Hey J., Kliman R. M. Population genetics and phylogenetics of DNA sequence variation at multiple loci within the Drosophila melanogaster species complex. Mol Biol Evol. 1993 Jul;10(4):804–822. doi: 10.1093/oxfordjournals.molbev.a040044. [DOI] [PubMed] [Google Scholar]
  22. Hutter C. M., Schug M. D., Aquadro C. F. Microsatellite variation in Drosophila melanogaster and Drosophila simulans: a reciprocal test of the ascertainment bias hypothesis. Mol Biol Evol. 1998 Dec;15(12):1620–1636. doi: 10.1093/oxfordjournals.molbev.a025890. [DOI] [PubMed] [Google Scholar]
  23. Irvin S. D., Wetterstrand K. A., Hutter C. M., Aquadro C. F. Genetic variation and differentiation at microsatellite loci in Drosophila simulans. Evidence for founder effects in new world populations. Genetics. 1998 Oct;150(2):777–790. doi: 10.1093/genetics/150.2.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kruglyak S., Durrett R. T., Schug M. D., Aquadro C. F. Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10774–10778. doi: 10.1073/pnas.95.18.10774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kruglyak S., Durrett R., Schug M. D., Aquadro C. F. Distribution and abundance of microsatellites in the yeast genome can Be explained by a balance between slippage events and point mutations. Mol Biol Evol. 2000 Aug;17(8):1210–1219. doi: 10.1093/oxfordjournals.molbev.a026404. [DOI] [PubMed] [Google Scholar]
  26. Kumar S., Hedges S. B. A molecular timescale for vertebrate evolution. Nature. 1998 Apr 30;392(6679):917–920. doi: 10.1038/31927. [DOI] [PubMed] [Google Scholar]
  27. Nauta M. J., Weissing F. J. Constraints on allele size at microsatellite loci: implications for genetic differentiation. Genetics. 1996 Jun;143(2):1021–1032. doi: 10.1093/genetics/143.2.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ohta T., Kimura M. A model of mutation appropriate to estimate the number of electrophoretically detectable alleles in a finite population. Genet Res. 1973 Oct;22(2):201–204. doi: 10.1017/s0016672300012994. [DOI] [PubMed] [Google Scholar]
  29. Pollock D. D., Bergman A., Feldman M. W., Goldstein D. B. Microsatellite behavior with range constraints: parameter estimation and improved distances for use in phylogenetic reconstruction. Theor Popul Biol. 1998 Jun;53(3):256–271. doi: 10.1006/tpbi.1998.1363. [DOI] [PubMed] [Google Scholar]
  30. Pritchard J. K., Seielstad M. T., Perez-Lezaun A., Feldman M. W. Population growth of human Y chromosomes: a study of Y chromosome microsatellites. Mol Biol Evol. 1999 Dec;16(12):1791–1798. doi: 10.1093/oxfordjournals.molbev.a026091. [DOI] [PubMed] [Google Scholar]
  31. Reich D. E., Goldstein D. B. Genetic evidence for a Paleolithic human population expansion in Africa. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8119–8123. doi: 10.1073/pnas.95.14.8119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rose O., Falush D. A threshold size for microsatellite expansion. Mol Biol Evol. 1998 May;15(5):613–615. doi: 10.1093/oxfordjournals.molbev.a025964. [DOI] [PubMed] [Google Scholar]
  33. Roy M. S., Geffen E., Smith D., Ostrander E. A., Wayne R. K. Patterns of differentiation and hybridization in North American wolflike canids, revealed by analysis of microsatellite loci. Mol Biol Evol. 1994 Jul;11(4):553–570. doi: 10.1093/oxfordjournals.molbev.a040137. [DOI] [PubMed] [Google Scholar]
  34. Rubinsztein D. C., Leggo J., Amos W. Microsatellites evolve more rapidly in humans than in chimpanzees. Genomics. 1995 Dec 10;30(3):610–612. doi: 10.1006/geno.1995.1285. [DOI] [PubMed] [Google Scholar]
  35. Ruiz-Linares A., Ortíz-Barrientos D., Figueroa M., Mesa N., Múnera J. G., Bedoya G., Vélez I. D., García L. F., Pérez-Lezaun A., Bertranpetit J. Microsatellites provide evidence for Y chromosome diversity among the founders of the New World. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6312–6317. doi: 10.1073/pnas.96.11.6312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Schug M. D., Hutter C. M., Wetterstrand K. A., Gaudette M. S., Mackay T. F., Aquadro C. F. The mutation rates of di-, tri- and tetranucleotide repeats in Drosophila melanogaster. Mol Biol Evol. 1998 Dec;15(12):1751–1760. doi: 10.1093/oxfordjournals.molbev.a025901. [DOI] [PubMed] [Google Scholar]
  37. Shriver M. D., Jin L., Boerwinkle E., Deka R., Ferrell R. E., Chakraborty R. A novel measure of genetic distance for highly polymorphic tandem repeat loci. Mol Biol Evol. 1995 Sep;12(5):914–920. doi: 10.1093/oxfordjournals.molbev.a040268. [DOI] [PubMed] [Google Scholar]
  38. Stefanini F. M., Feldman M. W. Bayesian estimation of range for microsatellite loci. Genet Res. 2000 Apr;75(2):167–177. doi: 10.1017/s0016672399004280. [DOI] [PubMed] [Google Scholar]
  39. Wierdl M., Dominska M., Petes T. D. Microsatellite instability in yeast: dependence on the length of the microsatellite. Genetics. 1997 Jul;146(3):769–779. doi: 10.1093/genetics/146.3.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Xu X., Peng M., Fang Z. The direction of microsatellite mutations is dependent upon allele length. Nat Genet. 2000 Apr;24(4):396–399. doi: 10.1038/74238. [DOI] [PubMed] [Google Scholar]
  41. Young E. T., Sloan J. S., Van Riper K. Trinucleotide repeats are clustered in regulatory genes in Saccharomyces cerevisiae. Genetics. 2000 Mar;154(3):1053–1068. doi: 10.1093/genetics/154.3.1053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Zhivotovsky L. A., Feldman M. W., Grishechkin S. A. Biased mutations and microsatellite variation. Mol Biol Evol. 1997 Sep;14(9):926–933. doi: 10.1093/oxfordjournals.molbev.a025835. [DOI] [PubMed] [Google Scholar]