Microsatellites: evolution and mutational processes

Microsatellites (simple sequence repeats) are ubiquitous in eukaryotic genomes, and they are highly polymorphic. They are currently the primary tools for most genetic mapping and for studies comparing the differentiation of human and other mammalian populations. More and more inherited human diseases are now recognized as resulting from mutations in particular microsatellites, and such microsatellite mutations can serve as markers for some cancers. The majority of microsatellite mutational changes probably consist of insertion or deletion of one or a few repeat units through replication slippage, whereas larger (much rarer) changes are important in producing observed allele distributions. Comparisons of microsatellite allele frequencies between humans and chimpanzees suggest that there are constraints on the overall length of microsatellites. Sequence analyses of microsatellites in diverse human and non-human populations indicate that the structure of many repeats may not be as simple as previously believed, in that alleles differ in base composition as well as in repeat length. Single base changes that result in long uninterrupted repeats may lead to increased mutation rates, including the extreme trinucleotide repeat instability responsible for several inherited diseases.