Abstract
Microsatellites, comprising tandemly repeated short nucleotide sequences, are ubiquitous in eukaryotic genomes. Mutations within microsatellites are frequent, altering their overall length by insertion or deletion of a small number of repeat units, with a rate as high as 10−3 in humans1. Despite their high mutability, stable allele frequency distributions are typically observed for microsatellites in humans as well as other primates2,3, although the mechanism maintaining these stable distributions remains unclear. Previous studies have suggested that microsatellite mutations occur more frequently in longer alleles and favour expansion4,5,6,7,8. Generalizing these results has been hindered because the sample sizes were small, only a small subset of alleles for any marker was studied and the direction of mutation (expansion or contraction) was not rigorously determined. Here we examine 236 mutations at 122 tetranucleotide repeat markers and find that the rate of contraction mutations increases exponentially with allele size, whereas the rate of expansion mutations is constant across the entire allele distribution. The overall rate of expansion mutations does not differ from that of contractions. Our findings offer an explanation for the stationary allele distribution of microsatellites.
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References
Weber, J.L. & Wong, C. Mutation of human short tandem repeats . Hum. Mol. Genet. 2, 1123– 1128 (1993).
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. 12, 594–603 ( 1995).
Goldstein, D.B. & Pollock, D.D. Launching microsatellites: a review of mutation processes and methods of phylogenetic interference. J. Hered. 88, 335–342 ( 1997).
Wierdl, M., Dominska, M. & Petes, T.D. Microsatellite instability in yeast: dependence on the length of the microsatellite. Genetics 146, 769–779 (1997).
Twerdi, C.D., Boyer, J.C. & Farber, R.A. Relative rates of insertion and deletion mutations in a microsatellite sequence in cultured cells. Proc. Natl Acad. Sci. USA 96, 2875–2879 ( 1999).
Brinkmann, B., Klintschar, M., Neuhuber, F., Huhne, J. & Rolf, B. Mutation rate in human microsatellites: influence of the structure and length of the tandem repeat. Am. J. Hum. Genet. 62, 1408–1415 (1998).
Primmer, C.R., Saino, N., Moller, A.P. & Ellegren, H. Directional evolution in germline microsatellite mutations. Nature Genet. 13, 391–393 (1996); erratum: 14, 133 (1996).
Amos, W., Sawcer, S.J., Feakes, R.W. & Rubinsztein, D.C. Microsatellites show mutational bias and heterozygote instability. Nature Genet. 13, 390–391 (1996).
Xu, X. et al. An extreme-sib-pair genome scan for genes regulating blood pressure . Am. J. Hum. Genet. 64, 1694– 1701 (1999).
Di Rienzo, A. et al. Mutational processes of simple-sequence repeat loci in human populations. Proc. Natl Acad. Sci. USA 91, 3166–3170 (1994).
Kimmel, M. & Chakraborty, R. Measures of variation at DNA repeat loci under a general stepwise mutation model. Theor. Popul. Biol. 50, 345–367 ( 1996).
Valdes, A.M., Slatkin, M. & Freimer, N.B. Allele frequencies at microsatellite loci: the stepwise mutation model revisited. Genetics 133, 737–749 (1993).
Zhivotovsky, L.A. & Feldman, M.W. Microsatellite variability and genetic distances. Proc. Natl Acad. Sci. USA 92, 11549–11552 (1995).
Levinson, G. & Gutman, G.A. Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Mol. Biol. Evol. 4, 203–221 (1987).
Sia, E.A., Kokoska, R.J., Dominska, M., Greenwell, P. & Petes, T.D. Microsatellite instability in yeast: dependence on repeat unit size and DNA mismatch repair genes. Mol. Cell. Biol. 17, 2851–2858 (1997).
Horvath, S. & Laird, N.M. A discordant-sibship test for disequilibrium and linkage: no need for parental data. Am. J. Hum. Genet. 63, 1886–1897 (1998).
Kruglyak, L., Daly, M.J., Reeve-Daly, M.P. & Lander, E.S. Parametric and nonparametric linkage analysis: a unified multipoint approach . Am. J. Hum. Genet. 58, 1347– 1363 (1996).
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Xu, X., Peng, M., Fang, Z. et al. The direction of microsatellite mutations is dependent upon allele length . Nat Genet 24, 396–399 (2000). https://doi.org/10.1038/74238
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DOI: https://doi.org/10.1038/74238
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