The effects of transcription and recombination on mutational dynamics of short tandem repeats

Abstract

Short tandem repeats (STR) are ubiquitous components of the genomic architecture of most living organisms. Recent work has highlighted the widespread functional significance of such repeats, particularly around gene regulation, but the mutational processes underlying the evolution of these highly abundant and highly variable sequences are not fully understood. Traditional models assume that strand misalignment during replication is the predominantmechanism, but empirical data suggest the involvement of other processes including recombination and transcription. Despite this evidence, the relative influences of these processes have not previously been tested experimentally on a genomewide scale. Using deep sequencing, we identify mutations at >200 microsatellites, across 700 generations in replicated populations of two otherwise identical sexual and asexual Saccharomyces cerevisiae strains. Using generalized linear models, we investigate correlates of STR mutability including the nature of the mutation, STR composition and contextual factors including recombination, transcription and replication origins. Sexual capability was not a significant predictor of microsatellite mutability, but, intriguingly, we identify transcription as a significant positive predictor. We also find that STR density is substantially increased in regions neighboring, but not within, recombination hotspots.