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Microsatellites: simple sequences with complex evolution

Key Points

  • Microsatellites, or tandem repeats of 1–6 bp, are abundant in the genomes of higher organisms and usually show high levels of polymorphism.

  • The density of microsatellites differs among species, as does the relative frequency of different repeat motifs.

  • Microsatellites are usually considered to be neutral markers and mainly occur in non-coding DNA.

  • Mutations in simple repeats lead to the insertion or deletion of one or a few repeat units, a situation that is broadly compatible with the stepwise mutation model.

  • One model of microsatellite evolution posits that stationary length distributions arise from a balance between length mutations, which tend to promote repeat growth, and point mutations, which tend to break long repeat arrays into smaller units.

  • The main mechanism of mutation is replication slippage, which results from the transient dissociation of the replicating DNA strands followed by misaligned reassociation.

  • Most primary mutations in microsatellites are corrected by the mismatch-repair system. Cells that are deficient in mismatch repair show highly elevated rates of microsatellite mutation.

  • Microsatellite mutation rate generally increases with repeat number.

  • Mutation rate heterogeneity among markers is significant, although the causes of this variation are not yet fully understood.

Abstract

Few genetic markers, if any, have found such widespread use as microsatellites, or simple/short tandem repeats. Features such as hypervariability and ubiquitous occurrence explain their usefulness, but these features also pose several questions. For example, why are microsatellites so abundant, why are they so polymorphic and by what mechanism do they mutate? Most importantly, what governs the intricate balance between the frequent genesis and expansion of simple repetitive arrays, and the fact that microsatellite repeats rarely reach appreciable lengths? In other words, how do microsatellites evolve?

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Figure 1: Microsatellite mutation models.
Figure 2: Replication slippage.
Figure 3: Microsatellite mutation rates in the human genome.

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Acknowledgements

The author would like to acknowledge two particularly helpful reviewers who provided useful comments on the manuscript. The author's work was supported in part by the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning.

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DATABASES

Entrez

MSH3

FURTHER INFORMATION

RepeatMasker

Sputnik

Tandem Repeats Finder

Glossary

HETEROZYGOSITY

The proportion of individuals in a population that carry two different alleles at a locus.

GENE FLOW

The transfer of alleles within and between populations that arises from migration and dispersal.

DENSITY GRADIENT CENTRIFUGATION

Separation of biomolecules on the basis of their density.

RETROTRANSPOSONS

Mobile elements that spread in the genome through an RNA intermediate.

EFFECTIVE POPULATION SIZE

The theoretical size of an idealized population that has the same magnitude of random genetic drift as the actual population.

SKEWNESS

Deviation from the normal distribution.

MISMATCH-REPAIR SYSTEM

An enzymatic system for the correction of errors that are introduced during DNA replication or recombination when an incorrect base is incorporated into the daughter strand, or when small insertion–deletion loops are being formed.

GENE CONVERSION

A meiotic process of directed change in which one allele directs the conversion of a partner allele to its own form.

TRANSCRIPTION-COUPLED REPAIR

Preferential repair of the transcribed strand of an active gene that is performed by excision-repair pathways.

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Ellegren, H. Microsatellites: simple sequences with complex evolution. Nat Rev Genet 5, 435–445 (2004). https://doi.org/10.1038/nrg1348

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