Skip to main content
Genetics logoLink to Genetics
. 2002 Jul;161(3):1339–1347. doi: 10.1093/genetics/161.3.1339

Deriving evolutionary relationships among populations using microsatellites and (deltamu)(2): all loci are equal, but some are more equal than others...

Pierre-Alexandre Landry 1, Mikko T Koskinen 1, Craig R Primmer 1
PMCID: PMC1462160  PMID: 12136035

Abstract

Numerous studies have relied on microsatellite DNA data to assess the relationships among populations in a phylogenetic framework, converting microsatellite allelic composition of populations into evolutionary distances. Among other coefficients, (deltamu)(2) and R(st) are often employed because they make use of the differences in allele sizes on the basis of the stepwise mutation model. While it has been recognized that some microsatellites can yield disproportionate interpopulation distance estimates, no formal investigation has been conducted to evaluate to what extent such loci could affect the topology of the corresponding dendrograms. Here we show that single loci, displaying extremely large among-population variance, can greatly bias the topology of the phylogenetic tree, using data from European grayling (Thymallus thymallus, Salmonidae) populations. Importantly, we also demonstrate that the inclusion of a single disproportionate locus will lead to an overestimation of the stability of trees assessed using bootstrapping. To avoid this bias, we introduce a simple statistical test for detecting loci with significantly disproportionate variance prior to phylogenetic analyses and further show that exclusion of offending loci eliminates the false increase in phylogram stability.

Full Text

The Full Text of this article is available as a PDF (109.0 KB).

Selected References

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

  1. Angers B., Bernatchez L. Complex evolution of a salmonid microsatellite locus and its consequences in inferring allelic divergence from size information. Mol Biol Evol. 1997 Mar;14(3):230–238. doi: 10.1093/oxfordjournals.molbev.a025759. [DOI] [PubMed] [Google Scholar]
  2. Balloux F., Brünner H., Lugon-Moulin N., Hausser J., Goudet J. Microsatellites can be misleading: an empirical and simulation study. Evolution. 2000 Aug;54(4):1414–1422. doi: 10.1111/j.0014-3820.2000.tb00573.x. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Calafell F., Shuster A., Speed W. C., Kidd J. R., Kidd K. K. Short tandem repeat polymorphism evolution in humans. Eur J Hum Genet. 1998 Jan;6(1):38–49. doi: 10.1038/sj.ejhg.5200151. [DOI] [PubMed] [Google Scholar]
  6. Cavalli-Sforza L. L., Edwards A. W. Phylogenetic analysis. Models and estimation procedures. Am J Hum Genet. 1967 May;19(3 Pt 1):233–257. [PMC free article] [PubMed] [Google Scholar]
  7. Cooper G., Amos W., Bellamy R., Siddiqui M. R., Frodsham A., Hill A. V., Rubinsztein D. C. An empirical exploration of the (delta mu)2 genetic distance for 213 human microsatellite markers. Am J Hum Genet. 1999 Oct;65(4):1125–1133. doi: 10.1086/302574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Crozier R. H., Kaufmann B., Carew M. E., Crozier Y. C. Mutability of microsatellites developed for the ant Camponotus consobrinus. Mol Ecol. 1999 Feb;8(2):271–276. doi: 10.1046/j.1365-294x.1999.00565.x. [DOI] [PubMed] [Google Scholar]
  9. Di Rienzo A., Donnelly P., Toomajian C., Sisk B., Hill A., Petzl-Erler M. L., Haines G. K., Barch D. H. Heterogeneity of microsatellite mutations within and between loci, and implications for human demographic histories. Genetics. 1998 Mar;148(3):1269–1284. doi: 10.1093/genetics/148.3.1269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ellegren H. Microsatellite mutations in the germline: implications for evolutionary inference. Trends Genet. 2000 Dec;16(12):551–558. doi: 10.1016/s0168-9525(00)02139-9. [DOI] [PubMed] [Google Scholar]
  11. Estoup A., Tailliez C., Cornuet J. M., Solignac M. Size homoplasy and mutational processes of interrupted microsatellites in two bee species, Apis mellifera and Bombus terrestris (Apidae). Mol Biol Evol. 1995 Nov;12(6):1074–1084. doi: 10.1093/oxfordjournals.molbev.a040282. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. 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]
  15. 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]
  16. Goodman S. J. Patterns of extensive genetic differentiation and variation among European harbor seals (Phoca vitulina vitulina) revealed using microsatellite DNA polymorphisms. Mol Biol Evol. 1998 Feb;15(2):104–118. doi: 10.1093/oxfordjournals.molbev.a025907. [DOI] [PubMed] [Google Scholar]
  17. Kayser M., Roewer L., Hedman M., Henke L., Henke J., Brauer S., Krüger C., Krawczak M., Nagy M., Dobosz T. Characteristics and frequency of germline mutations at microsatellite loci from the human Y chromosome, as revealed by direct observation in father/son pairs. Am J Hum Genet. 2000 Apr 6;66(5):1580–1588. doi: 10.1086/302905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kimmel M., Chakraborty R., Stivers D. N., Deka R. Dynamics of repeat polymorphisms under a forward-backward mutation model: within- and between-population variability at microsatellite loci. Genetics. 1996 May;143(1):549–555. doi: 10.1093/genetics/143.1.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koskinen M. T., Nilsson J., Veselov A. Je, Potutkin A. G., Ranta E., Primmer C. R. Microsatellite data resolve phylogeographic patterns in European grayling, Thymallus thymallus, Salmonidae. Heredity (Edinb) 2002 May;88(5):391–401. doi: 10.1038/sj.hdy.6800072. [DOI] [PubMed] [Google Scholar]
  20. Koskinen M. T., Ranta E., Piironen J., Veselov A., Titov S., Haugen T. O., Nilsson J., Carlstein M., Primmer C. R. Genetic lineages and postglacial colonization of grayling (Thymallus thymallus, Salmonidae) in Europe, as revealed by mitochondrial DNA analyses. Mol Ecol. 2000 Oct;9(10):1609–1624. doi: 10.1046/j.1365-294x.2000.01065.x. [DOI] [PubMed] [Google Scholar]
  21. Lehmann T., Hawley W. A., Collins F. H. An evaluation of evolutionary constraints on microsatellite loci using null alleles. Genetics. 1996 Nov;144(3):1155–1163. doi: 10.1093/genetics/144.3.1155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nei M., Tajima F., Tateno Y. Accuracy of estimated phylogenetic trees from molecular data. II. Gene frequency data. J Mol Evol. 1983;19(2):153–170. doi: 10.1007/BF02300753. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Primmer C. R., Saino N., Møller A. P., Ellegren H. Directional evolution in germline microsatellite mutations. Nat Genet. 1996 Aug;13(4):391–393. doi: 10.1038/ng0896-391. [DOI] [PubMed] [Google Scholar]
  26. Ritz L. R., Glowatzki-Mullis M. L., MacHugh D. E., Gaillard C. Phylogenetic analysis of the tribe Bovini using microsatellites. Anim Genet. 2000 Jun;31(3):178–185. doi: 10.1046/j.1365-2052.2000.00621.x. [DOI] [PubMed] [Google Scholar]
  27. Schlötterer C. Evolutionary dynamics of microsatellite DNA. Chromosoma. 2000 Sep;109(6):365–371. doi: 10.1007/s004120000089. [DOI] [PubMed] [Google Scholar]
  28. Schlötterer C., Ritter R., Harr B., Brem G. High mutation rate of a long microsatellite allele in Drosophila melanogaster provides evidence for allele-specific mutation rates. Mol Biol Evol. 1998 Oct;15(10):1269–1274. doi: 10.1093/oxfordjournals.molbev.a025855. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Shriver M. D., Jin L., Chakraborty R., Boerwinkle E. VNTR allele frequency distributions under the stepwise mutation model: a computer simulation approach. Genetics. 1993 Jul;134(3):983–993. doi: 10.1093/genetics/134.3.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Slatkin M. A measure of population subdivision based on microsatellite allele frequencies. Genetics. 1995 Jan;139(1):457–462. doi: 10.1093/genetics/139.1.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Takezaki N., Nei M. Genetic distances and reconstruction of phylogenetic trees from microsatellite DNA. Genetics. 1996 Sep;144(1):389–399. doi: 10.1093/genetics/144.1.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Valdes A. M., Slatkin M., Freimer N. B. Allele frequencies at microsatellite loci: the stepwise mutation model revisited. Genetics. 1993 Mar;133(3):737–749. doi: 10.1093/genetics/133.3.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Weber J. L., Wong C. Mutation of human short tandem repeats. Hum Mol Genet. 1993 Aug;2(8):1123–1128. doi: 10.1093/hmg/2.8.1123. [DOI] [PubMed] [Google Scholar]
  35. Zhivotovsky L. A. Estimating divergence time with the use of microsatellite genetic distances: impacts of population growth and gene flow. Mol Biol Evol. 2001 May;18(5):700–709. doi: 10.1093/oxfordjournals.molbev.a003852. [DOI] [PubMed] [Google Scholar]
  36. Zhivotovsky L. A., Feldman M. W. Microsatellite variability and genetic distances. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11549–11552. doi: 10.1073/pnas.92.25.11549. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES