Mutation and selection processes regulating short tandem repeats give rise to genetic and phenotypic diversity across species.

This article provides a comprehensive review of short tandem repeats (STRs), which are DNA sequences of 1–6 base pairs repeated in tandem and represent highly mutable genomic elements contributing to genetic and phenotypic diversity within and across species. It details the molecular mechanisms driving STR mutations—primarily strand slippage and DNA repair processes—and how these lead to characteristic patterns of STR variation constrained by biochemical and selective forces. The review further explores comparative genomics findings on STR abundance and distribution across eukaryotes and prokaryotes, highlighting their enrichment in non-coding regions and functional roles in gene regulation and protein structure. Finally, it discusses the emerging evidence for STRs' influence on complex traits, challenges in detecting natural selection on STR loci due to their high mutation rates, and recent methodological advances enabling genome-wide analyses of STR variation and selection.