Evolution of Microsatellites


Microsatellites are tandem repeats of short nucleotide sequence (1–6 bp) and abundant in the eukaryotic genome. Mutation rate is high (10−2–10−6 per locus per generation), and there is large variation among species. Mutational changes of microsatellites are mostly repeat number change by one. However, there are some multistep changes, and the mutation rate shows a complex relationship with repeat length, repeat unit size and motif composition. Microsatellites are useful to study the evolutionary relationship among populations. Genetic distance, a measure of the extent of genetic differentiation between populations, calculated for human populations appears to increase approximately linearly with the time after population divergence. Interestingly, the total number of repeats of microsatellite loci in an individual's genome also appears to diverge with the time after population divergence. Variation of repeat number in microsatellite loci contributes the variation of genome size of an individual due to its abundance in the genome.

Key Concepts:

  • Microsatellites are tandem repeats of short nucleotide sequence (1 – 6 bp) and abundant in eukaryotic genome.

  • The mutational changes of microsatellites are mostly increase or decrease of the repeat number by one.

  • The repeat number change of microsatellite occurs through a mechanism called replication slippage.

  • The mutational pattern of microsatellites roughly follows the stepwise mutation model.

  • The equilibrium distribution of repeat number in miscrosatellites may be obtained by balance between replication slippage and disruption of repeats by point mutation as well as by balance between higher expansion rate over contraction rate for short repeats and higher contraction rate over expansion rate for longer repeats.

  • The mutation rate of microsatellites varies with size and motif of repeat unit.

  • The mutation rate and repeat length of microsatellites vary among species.

  • Genetic distance of microsatellites increases proportionally with the time after human population divergence.

  • The average difference of total repeat number of individuals between populations increases with time after population divergence.

  • Contribution of the repeat number variation of microsatellites to genome size variation may be quite large.

Keywords: mutational mechanism; mutational model; genetic distance; stepwise mutation model; population divergence; repeat number variation; genome size; human population

Figure 1.

Schematic illustration of replication slippage. (a) Normal replication. (b) Increase of repeat number. (c) Decrease of repeat number. During replication, misalignment of the template strand and the daughter strand results in the change of repeat number. If the bubble‐like structure is made in the daughter strand (b), the mismatch repair occurs in the misaligned region, and it results in increase of the repeat number. If the bubble‐like structure is made in the template strand, it results in decrease of the repeat number.



Bowcock AM, Ruiz‐Linares A, Tomfohrde J et al. (1994) High resolution of human evolutionary trees with polymorphic microsatellites. Nature 368: 455–457.

Calabrese P and Durrett R (2003) Dinucleotide repeats in the Drosophila and human genomes have complex, length‐dependent mutation processes. Molecular Biology and Evolution 20: 715–725.

Cann RL, Stoneking M and Wilson AC (1987) Mitochondrial DNA and human evolution. Nature 325: 31–36.

Chakraborty R, Kimmel M, Stivers DN et al. (1997) Relative mutation rates at di‐, tri‐, and tetranucleotide microsatellite loci. Proceedings of the National Academy of Sciences of the USA 94: 1041–1046.

Chakraborty R and Nei M (1982) Genetic differentiation of quantitative characters between populations or species. Genetical Research 39: 303–314.

Di Rienzo A, Peterson AC, Garza JC et al. (1994) Mutational processes of simple‐sequence repeat loci in human populations. Proceedings of the National Academy of Sciences of the USA 91: 3166–3170.

Eckert KA and Hile SE (2009) Every microsatellite is different: intrinsic DNA features dictate mutagenesis of common microsatellites present in the human genome. Molecular Carcinogenesis 48: 379–388.

Ellegren H (2000) Microsatellite mutations in the germline: implications for evolutionary inference. Trends in Genetics 16: 551–558.

Ellegren H (2004) Microsatellites: simple sequences with complex evolution. Nature Reviews. Genetics 5: 435–445.

Garza JC, Slatkin M and Freimer NB (1995) Microsatellite allele frequencies in human and chimpanzees, with implications for constraints on allele size. Molecular Biology and Evolution 12: 594–603.

Goldstein DB and Pollock DD (1997) Launching microsatellites: a review of mutation processes and methods of phylogenetic inference. Journal of Heredity 88: 335–342.

Goldstein DB, Ruiz Linares A, Cavalli‐Sforza LL et al. (1995) Genetic absolute dating based on microsatellites and the origin of modern humans. Proceedings of the National Academy of Sciences of the USA 92: 6723–6727.

Hancock JM (1996) Simple sequences in a ‘minimal’ genome. Nature Genetics 14: 14–15.

International Human Genome Sequencing Consortium (2001) Initial sequencing of analysis of the human genome. Nature 409: 860–921.

Kelkar YD, Tyekucheva S, Chiaromonte F et al. (2008) The genome‐wide determinants of human and chimpanzee microsatellite evolution. Genome Research 18: 30–38.

Kimmel M, Chakraborty R, Stivers DN et al. (1996) Dynamics of repeat polymorphisms under a forward‐backward mutation model: within‐ and between‐population variability at microsatellite loci. Genetics 143: 549–555.

Kimura M and Crow JF (1964) The numbers of alleles that can be maintained in a finite population. Genetics 49: 523–538.

Kruglyak S, Durrett R, Schug MD et al. (1998) Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations. Proceedings of the National Academy of Sciences of the USA 95: 10774–10778.

Lai Y and Sun F (2003) The relationship between microsatellite slippage mutation rate and the number of repeat units. Molecular Biology and Evolution 20: 2123–2131.

Morgante M, Hanatey M and Powell W (2002) Microsatellites are preferentially associated with nonrepetitive DNA in plant genomes. Nature Genetics 30: 194–200.

Mouse Genome Sequencing Consortium (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520–562.

Nei M (1972) Genetic distance between populations. American Naturalist 106: 203–291.

Nei M and Kumar S (2000) Molecular Evolution and Phylogenetics. Oxford: Oxford University Press.

Nei M and Roychoudhury AK (1982) Genetic relationship and evolution of human races. Evolutionary Biology 14: 1–59.

Ohta T and Kimura M (1973) A model of mutation appropriate to estimate the number of electrophoretically detectable alleles in a finite population. Genetical Research 22: 201–204.

Pearson CE, Edamura KN and Cleary JD (2005) Repeat instability: mechanisms of dynamic mutations. Nature Reviews. Genetics 6: 729–742.

Ramachandran S, Deshpande O, Roseman CC et al. (2005) Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa. Proceedings of the National Academy of Sciences of the USA 102: 15942–15947.

Rat Genome Sequencing Project Consortium (2004) Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428: 493–521.

Rubinsztein DC, Amos W, Leggo J et al. (1995) Microsatellite evolution – evidence for directionality and variation in rate between species. Nature Genetics 10: 337–343.

Schlötterer C (2000) Evolutionary dynamics of microsatellite DNA. Chromosoma 109: 365–371.

Schug MD, Hutter CM, Wetterstrand KA et al. (1998) The mutation rates of di‐, tri‐ and tetranucleotide repeats in Drosophila melanogaster. Molecular Biology and Evolution 15: 1751–1760.

Shriver MD, Jin L, Chakraborty C et al. (1993) VNTR allele frequency distributions under the stepwise mutation model: a computer simulation approach. Genetics 154: 983–993.

Sibly RM, Whittaker JC and Talbot M (2001) A maximum‐likelihood approach to fitting equilibrium models of microsatellite evolution. Molecular Biology and Evolution 18: 413–417.

Takezaki N and Nei M (2009) Genomic drift and evolution of microsatellite DNAs in human populations. Molecular Biology and Evolution 26: 1835–1840.

Tero N, Neumeier H, Gudavalli R et al. (2006) Silene tatarica microsatellites are frequently located in repetitive DNA. Journal of Evolutionary Biology 19: 1612–1619.

Toth G, Gaspari Z and Jurka J (2000) Microsatellites in different eukaryotic genomes: survey and analysis. Genome Research 10: 967–981.

Valdes AM, Slatkin M and Freimer N (1993) Allele frequencies at microsatellite loci: the stepwise mutation model revisited. Genetics 133: 737–749.

Vowles EJ and Amos W (2006) Quantifying ascertainment bias and species‐specific length differences in human and chimpanzee microsatellites using genome sequences. Molecular Biology and Evolution 23: 598–607.

Warren WC, Hillier LW, Graves JAM et al. (2008) Genome analysis of the platypus reveals unique signatures of evolution. Nature 453: 175–183.

Webster MT, Smith NGC and Ellegren H (2002) Microsatellite evolution inferred from human‐chimpanzee genomic sequence alignments. Proceedings of the National Academy of Sciences of the USA 99: 8748–8753.

Further Reading

DeSalle R and Amato G (2004) The expansion of conservation genetics. Nature Reviews. Genetics 5: 702–712.

Goldstein DB and Schlötterer C (1999) Microsatellite: evolution and applications. Oxford: Oxford University Press.

Schlötterer C (2004) The evolution of molecular markers – just a matter of fashion? Nature Reviews. Genetics 5: 63–69.

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Takezaki, Naoko(Oct 2010) Evolution of Microsatellites. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022866]