More single-nucleotide mutations surround small insertions than small deletions in primates

Abstract

Early studies have shown that single-nucleotide mutation rates increase close to insertions and deletions, but it is not fully understood how natural selection shapes genome-wide patterns of indels and their nearby single-nucleotide mutations. In this study, we find that, in primates, more single-nucleotide mutations surround small insertions than small deletions. This pattern affects <150 base pair (bp) sequences close to indels and persists under different genomic properties, such as exon/intron/intergenic contexts, repeated/nonrepeated sequences, replication timing, recombination rates, indel density, and guanine-cytosine (GC) content. We propose two different, but not mutually exclusive, hypothetical mechanisms to explain the pattern. One mechanism is that the sequence context preferring insertion formation may also favor nucleotide substitutions. Another mechanism is related to a hypothesis in which indel heterozygosity tends to increase nearby nucleotide substitution rates. It means that if insertions spend more time in heterozygotes, insertions may accumulate more surrounding single-nucleotide changes. In conclusion, we characterize a special genome-wide evolutionary pattern for indels and nearby single-nucleotide changes. This pattern may be driven by natural selection and bias primates' genome evolution and phenotypic variations.