Short indels are subject to insertion-biased gene conversion.

Recombination between homologous loci is accompanied by formation of heteroduplexes. Repairing mismatches in heteroduplexes often leads to single nucleotide substitutions in a process known as gene conversion. Gene conversion was shown to be GC-biased in different organisms; that is, a W(A or T)→S(G or C) substitution is more likely in this process than a S→W substitution. Here, we show that the insertion/deletion ratio for short noncoding indels that reach fixation between species is positively correlated with the recombination rate in Drosophila melanogaster, Homo sapiens, and Saccharomyces cerevisiae. This correlation is both due to an increase of the fixation rate of insertions and decrease of the fixation rate of deletions in regions of high recombination. Whole-genome data on indel polymorphism and divergence in D. melanogaster rule out mutation biases and selection as the cause of this trend, pointing to insertion-biased gene conversion as the most likely explanation. The bias toward insertions is the strongest for single-nucleotide indels, and decreases with indel length. In regions of high recombination rate this bias leads to an up to ∼5-fold excess of fixed short insertions over deletions, and substantially affects the evolution of DNA segments.