Genomewide Association between Insertions/Deletions and the Nucleotide Diversity in Bacteria

Spontaneous mutations are not randomly distributed throughout a genome. Although mutation hotspots are found on genomes of a variety of species, mechanisms that generate the hotspots are not well understood. In eukaryotes, strong association between a regional nucleotide substitution rate and insertions/deletions (indels) was reported in a previous study, and the "indel-induced mutation" hypothesis was proposed. However, it is unknown whether the association exists even in prokaryote genomes. In this study, we conducted a systematic survey for the association in 262 complete genomes from 73 bacterial species. In these bacteria, the level of nucleotide diversity was negatively correlated with the distance from the closest indel, which is consistent with the eukaryote data. The same pattern was observed even after excluding noncoding sequences, indicating that the difference in functional constraints among genomic regions is not a primary cause of the correlation. In addition, the increase of nucleotide substitution rate was detected disproportionally on a lineage carrying a derived indel mutation, confirming the indel-nucleotide diversity association in the bacterial genomes. In some cases, the level of nucleotide diversity was more than 100 times higher in regions close to indels than in distant regions. Although further understanding of the molecular mechanism is required to test the hypothesis, these results suggest that the same mechanism for the indel-nucleotide diversity associations might exist in eukaryotes and prokaryotes and play an important role in molecular evolution.