Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations

Abstract

We describe and test a Markov chain model of microsatellite evolution that can explain the different distributions of microsatellite lengths across different organisms and repeat motifs. Two key features of this model are the dependence of mutation rates on microsatellite length and a mutation process that includes both strand slippage and point mutation events. We compute the stationary distribution of allele lengths under this model and use it to fit DNA data for di-, tri-, and tetranucleotide repeats in humans, mice, fruit f lies, and yeast. The best fit results lead to slippage rate estimates that are highest in mice, followed by humans, then yeast, and then fruit f lies. Within each organism, the estimates are highest in di-, then tri-, and then tetranucleotide repeats. Our estimates are consistent with experimentally determined mutation rates from other studies. The results suggest that the different length distributions among organisms and repeat motifs can be explained by a simple difference in slippage rates and that selective constraints on length need not be imposed.

Signatures of selection in mammalian clock genes with coding trinucleotide repeats: Implications for studying the genomics of high‐pace adaptation

“…It is possible that the expansion of cTNRs in both domestic and wild species that do not use photoperiod to cue life‐history events could be caused by the lifting of evolutionary constraints on repeat size; however, this idea remains largely unsupported. Further, the considerable purity of these long repeats supports the claim that increased purity is the mechanism by which cTNRs mutate (Ananda et al., 2014; Gemayel et al., 2012; Kruglyak et al., 1998). Thus, it is plausible that the removal of selective constraints, due to domestication or nonreliance on photoperiod, has removed the necessity for stable repeat structures to avoid maladaptation and thus facilitated the expansion of cTNRs in these species.…”

“…The mutational mechanism of cTNR structures has been associated with the purity of the repeat structure itself, where purer repeats are more likely to undergo further slippage (Kruglyak, Durrett, Schug, & Aquadro, 1998). This may be of adaptive value by generating phenotypic variation upon which selection can act (Kashi & King, 2006; Laidlaw et al., 2007).…”

Microsatellite variation among divergent populations of stalk-eyed flies, genus Cyrtodiopsis

“…One hypothesis is that many protocols favor the isolation of microsatellites with long repeat arrays, which tend to be more variable than shorter arrays . Longer repeat arrays also tend to be rarer than short arrays, perhaps because of biases in mutation mechanisms that favor smaller repeat array sizes (Kruglyak et al, 1998;Eisen, 1999 ;Estoup & Cornuet, 1999 ;Falush & Iwasa, 1999 ;. Thus, there should be a tendency for long microsatellites isolated in the source population to decline in both length and variability in more distant populations and species Pascual et al, 2000).…”

A review on SNP and other types of molecular markers and their use in animal genetics

“…Also, the much higher mutation rate of microsatellites, estimated to be as high as 1 × 10 −5 [42] when compared to the 1 × 10 −9 for SNPs [48,57], can be a concern, especially for association and linkage disequilibrium studies.…”