Heterogeneity in the rate and pattern of germline mutation at individual microsatellite loci

Abstract

There is a lack of information on how individual microsatellite loci differ with respect to their mutation properties. Such variation will have an important bearing on our understanding of the ubiquitous occurrence of simple repeat sequences in eukaryotic genomes and on deriving proper mutation models that can be incorporated into genetic distance estimates. We genotyped ∼ 100 families of the bird barn swallow (Hirundo rustica) for two hypervariable (heterozygosity >95%) microsatellite markers: HrU6, an (AAAG)n tetranucleotide repeat, and HrU10, an (AAGAG)n pentanucleotide repeat. A total of 27 germline mutation events were documented, corresponding to mutation rates of 0.57% (HrU6) and 1.56% (HrU10). The mutation rate increased with allele size, at ∼ 0.1% per repeat unit over the observed range of allele sizes (∼10-100 repeat units). Single repeat unit changes dominated, with 21/27 mutations representing the gain or loss of one repeat unit. There was no clear difference in the number of gains versus losses nor was there an effect of allele size on the magnitude or direction of mutation. Unexpectedly, the mutation rate of females (maternally transmitted mutations) was 2.5-5 times higher than that of males. Contrasting these observations with mutation data from other microsatellite loci reveals differences not only in the mutation rate, but also in the magnitude, direction and effect of sex on mutation. Thus, microsatellite mutation and evolution may be viewed as a dynamic and variable process.