Evolution of Microsatellite DNA


Microsatellites are highly mutable nucleotide arrays composed of short motifs repeated in tandem. They are ubiquitously distributed in bacterial and eukaryotic genomes and their abundance and mutability has made them a widely used genetic marker for a variety of applications. One aim of the study of microsatellite evolution is to predict their mutational patterns in order to make them more accurate markers of genetic distance between species or individuals. Applications that use microsatellites as markers work under the basic assumption that microsatellite mutations are simple and random. However, this assumption contrasts with the observed variability of mutation rates across microsatellite loci. Several factors such as array size and sequence motif have been shown to influence microsatellite mutation rates, but research into their evolution is also complicated by the fact that some microsatellites function to regulate gene expression and possibly other genomic functions, and may therefore be subject to selective pressure.

Key Concepts:

  • Microsatellites are arrays of tandemly repeated 1–6 bp sequence motifs. They are highly abundant in all organisms studied, and they are also highly polymorphic as a result of frequent change of length mutations.

  • The traditional view of microsatellites as neutrally evolving junk DNA is overly simplistic, which sometimes affects the accuracy of studies that use them as genetic markers.

  • Many complex processes interact to govern the frequency with which microsatellites mutate, including array length, sequence motif and flanking sequence.

  • Increasing evidence indicates that a subset of microsatellites function to regulate gene expression, and perhaps also interchromosomal recombination, and the evolution of these microsatellites is therefore influenced by selection.

  • The mutability of microsatellites, the fact that their mutations are easily reversible, and their abundance and conservation in regulatory regions suggest that they may make a significant contribution to the diversity and adaptation of species, but much work remains to establish the extent of their functional importance.

Keywords: tandem repeats; strand slippage; DNA ; microsatellite; polymorphism; mutation model; selection; gene; expression; strand slippage; repetitive

Figure 1.

Factors and processes affecting microsatellite mutation. Factors (italics) operate at different hierarchical levels (orange boxes), starting from the smallest scale, the microsatellite locus itself and moving up to the species level. Selection operates across all levels. All these factors interact dynamically, affecting the rate of replication slippage and recombination and, therefore, microsatellite variability.

Figure 2.

Models of tandem repeat length mutation. Unequal crossover, involving misalignment of homologous chromosomes or sister chromatids (a), and strand slippage (b) are the two main types of mechanism that have been proposed. Strand slippage can occur during any process requiring DNA synthesis, including recombination (c).

Figure 3.

Functional implications of microsatellite length change. Microsatellite length variations have been shown to mediate diverse functions depending on the genomic region in which these are present. Within exons microsatellite mutations can induce changes in protein structure, therefore altering its function, or can directly inactivate the protein by truncation or fusion of open reading frames (ORFs). Within introns and intergenic regions, these changes can partake in the modulation of gene expression, either by modifying the structure of transcription factors or enzymes involved in transcription modulation, or by changing the secondary and/or tertiary structure of DNA or RNA regions that interact with transcription factors. Furthermore, microsatellites are involved in the regulation of their own and genome‐wide mutation rates, by being present within the minor components of the MMR system.



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Further Reading

Buschiazzo E and Gemmell NJ (2006) The rise, fall and renaissance of microsatellites in eukaryotic genomes. BioEssays 28: 1040–1050.

Caporale LH (2006) The Implicit Genome. New York: Oxford University Press.

Gemayel R , Vinces MD , Legendre M and Verstrepen KJ (2010) Variable tandem repeats accelerate evolution of coding and regulatory sequences. Annual Reviews of Genetics 44: 445–477.

Kashi Y and King DG (2006) Simple sequence repeats as advantageous mutators in evolution. Trends in Genetics 22: 253–259.

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Jentzsch, Iris M Vargas, Bagshaw, Andrew TM, Buschiazzo, Emmanuel, Merkel, Angelika, and Gemmell, Neil J(Sep 2013) Evolution of Microsatellite DNA . In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020847.pub2]