• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Apr 2003; 163(4): 1467–1482.
PMCID: PMC1462522

Microsatellite allele sizes: a simple test to assess their significance on genetic differentiation.

Abstract

The mutation process at microsatellite loci typically occurs at high rates and with stepwise changes in allele sizes, features that may introduce bias when using classical measures of population differentiation based on allele identity (e.g., F(ST), Nei's Ds genetic distance). Allele size-based measures of differentiation, assuming a stepwise mutation process [e.g., Slatkin's R(ST), Goldstein et al.'s (deltamu)(2)], may better reflect differentiation at microsatellite loci, but they suffer high sampling variance. The relative efficiency of allele size- vs. allele identity-based statistics depends on the relative contributions of mutations vs. drift to population differentiation. We present a simple test based on a randomization procedure of allele sizes to determine whether stepwise-like mutations contributed to genetic differentiation. This test can be applied to any microsatellite data set designed to assess population differentiation and can be interpreted as testing whether F(ST) = R(ST). Computer simulations show that the test efficiently identifies which of F(ST) or R(ST) estimates has the lowest mean square error. A significant test, implying that R(ST) performs better than F(ST), is obtained when the mutation rate, mu, for a stepwise mutation process is (a) >/= m in an island model (m being the migration rate among populations) or (b) >/= 1/t in the case of isolated populations (t being the number of generations since population divergence). The test also informs on the efficiency of other statistics used in phylogenetical reconstruction [e.g., Ds and (deltamu)(2)], a nonsignificant test meaning that allele identity-based statistics perform better than allele size-based ones. This test can also provide insights into the evolutionary history of populations, revealing, for example, phylogeographic patterns, as illustrated by applying it on three published data sets.

Full Text

The Full Text of this article is available as a PDF (193K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Estoup A, Rousset F, Michalakis Y, Cornuet JM, Adriamanga M, Guyomard R. Comparative analysis of microsatellite and allozyme markers: a case study investigating microgeographic differentiation in brown trout (Salmo trutta). Mol Ecol. 1998 Mar;7(3):339–353. [PubMed]
  • Estoup Arnaud, Jarne Philippe, Cornuet Jean-Marie. Homoplasy and mutation model at microsatellite loci and their consequences for population genetics analysis. Mol Ecol. 2002 Sep;11(9):1591–1604. [PubMed]
  • Freville H, Justy F, Olivieri I. Comparative allozyme and microsatellite population structure in a narrow endemic plant species, Centaurea corymbosa Pourret (Asteraceae). Mol Ecol. 2001 Apr;10(4):879–889. [PubMed]
  • Gaggiotti OE, Lange O, Rassmann K, Gliddon C. A comparison of two indirect methods for estimating average levels of gene flow using microsatellite data. Mol Ecol. 1999 Sep;8(9):1513–1520. [PubMed]
  • Balloux F. EASYPOP (version 1.7): a computer program for population genetics simulations. J Hered. 2001 May-Jun;92(3):301–302. [PubMed]
  • Goldstein DB, Pollock DD. Launching microsatellites: a review of mutation processes and methods of phylogenetic interference. J Hered. 1997 Sep-Oct;88(5):335–342. [PubMed]
  • Balloux F, Goudet J. Statistical properties of population differentiation estimators under stepwise mutation in a finite island model. Mol Ecol. 2002 Apr;11(4):771–783. [PubMed]
  • Goldstein DB, Ruiz Linares A, Cavalli-Sforza LL, Feldman MW. 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. [PMC free article] [PubMed]
  • Balloux François, Lugon-Moulin Nicolas. The estimation of population differentiation with microsatellite markers. Mol Ecol. 2002 Feb;11(2):155–165. [PubMed]
  • Goldstein DB, Ruiz Linares A, Cavalli-Sforza LL, Feldman MW. An evaluation of genetic distances for use with microsatellite loci. Genetics. 1995 Jan;139(1):463–471. [PMC free article] [PubMed]
  • Burban C, Petit RJ, Carcreff E, Jactel H. Rangewide variation of the maritime pine bast scale matsucoccus feytaudi duc. (Homoptera: matsucoccidae) in relation to the genetic structure of its host. Mol Ecol. 1999 Oct;8(10):1593–1602. [PubMed]
  • Charbonnel N, Angers B, Rasatavonjizay R, Bremond P, Debain C, Jarne P. The influence of mating system, demography, parasites and colonization on the population structure of Biomphalaria pfeifferi in Madagascar. Mol Ecol. 2002 Nov;11(11):2213–2228. [PubMed]
  • Heuertz M, Hausman JF, Tsvetkov I, Frascaria-Lacoste N, Vekemans X. Assessment of genetic structure within and among Bulgarian populations of the common ash (Fraxinus excelsior L.). Mol Ecol. 2001 Jul;10(7):1615–1623. [PubMed]
  • Colas B, Olivieri I, Riba M. Centaurea corymbosa, a cliff-dwelling species tottering on the brink of extinction: a demographic and genetic study. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3471–3476. [PMC free article] [PubMed]
  • Kimmel M, Chakraborty R. Measures of variation at DNA repeat loci under a general stepwise mutation model. Theor Popul Biol. 1996 Dec;50(3):345–367. [PubMed]
  • Kimmel M, Chakraborty R, Stivers DN, 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. [PMC free article] [PubMed]
  • Crow JF, Aoki K. Group selection for a polygenic behavioral trait: estimating the degree of population subdivision. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6073–6077. [PMC free article] [PubMed]
  • Lehmann T, Hawley WA, Collins FH. An evaluation of evolutionary constraints on microsatellite loci using null alleles. Genetics. 1996 Nov;144(3):1155–1163. [PMC free article] [PubMed]
  • Deka R, Guangyun S, Smelser D, Zhong Y, Kimmel M, Chakraborty R. Rate and directionality of mutations and effects of allele size constraints at anonymous, gene-associated, and disease-causing trinucleotide loci. Mol Biol Evol. 1999 Sep;16(9):1166–1177. [PubMed]
  • Michalakis Y, Excoffier L. A generic estimation of population subdivision using distances between alleles with special reference for microsatellite loci. Genetics. 1996 Mar;142(3):1061–1064. [PMC free article] [PubMed]
  • Michalakis Y, Veuille M. Length variation of CAG/CAA trinucleotide repeats in natural populations of Drosophila melanogaster and its relation to the recombination rate. Genetics. 1996 Aug;143(4):1713–1725. [PMC free article] [PubMed]
  • Pons O, Petit RJ. Measuring and testing genetic differentiation with ordered versus unordered alleles. Genetics. 1996 Nov;144(3):1237–1245. [PMC free article] [PubMed]
  • Renwick A, Davison L, Spratt H, King JP, Kimmel M. DNA dinucleotide evolution in humans: fitting theory to facts. Genetics. 2001 Oct;159(2):737–747. [PMC free article] [PubMed]
  • Whitlock MC, McCauley DE. Indirect measures of gene flow and migration: FST not equal to 1/(4Nm + 1). Heredity (Edinb) 1999 Feb;82(Pt 2):117–125. [PubMed]
  • Reynolds J, Weir BS, Cockerham CC. Estimation of the coancestry coefficient: basis for a short-term genetic distance. Genetics. 1983 Nov;105(3):767–779. [PMC free article] [PubMed]
  • Wierdl M, Dominska M, Petes TD. Microsatellite instability in yeast: dependence on the length of the microsatellite. Genetics. 1997 Jul;146(3):769–779. [PMC free article] [PubMed]
  • Ross KG, Krieger MJ, Shoemaker DD, Vargo EL, Keller L. Hierarchical analysis of genetic structure in native fire ant populations: results from three classes of molecular markers. Genetics. 1997 Oct;147(2):643–655. [PMC free article] [PubMed]
  • Xu X, Peng M, Fang Z. The direction of microsatellite mutations is dependent upon allele length. Nat Genet. 2000 Apr;24(4):396–399. [PubMed]
  • Rousset F. Genetic differentiation and estimation of gene flow from F-statistics under isolation by distance. Genetics. 1997 Apr;145(4):1219–1228. [PMC free article] [PubMed]
  • Zhivotovsky LA, Feldman MW. Microsatellite variability and genetic distances. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11549–11552. [PMC free article] [PubMed]
  • Zhivotovsky LA, Feldman MW, Grishechkin SA. Biased mutations and microsatellite variation. Mol Biol Evol. 1997 Sep;14(9):926–933. [PubMed]
  • Slatkin M. A measure of population subdivision based on microsatellite allele frequencies. Genetics. 1995 Jan;139(1):457–462. [PMC free article] [PubMed]
  • Zhu Y, Strassmann JE, Queller DC. Insertions, substitutions, and the origin of microsatellites. Genet Res. 2000 Dec;76(3):227–236. [PubMed]
  • Takezaki N, Nei M. Genetic distances and reconstruction of phylogenetic trees from microsatellite DNA. Genetics. 1996 Sep;144(1):389–399. [PMC free article] [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...