PRDM9 and an Epidemic of Gene Conversion and Non-Homologous Recombination among Alu Elements in Ancestral Gorillas

We performed a genome-wide scan for recombination-mediated interlocus gene conversion and deletion events among a set of orthologous Alu loci in the Great Apes, and were surprised to discover an extreme excess of such events in the gorilla lineage versus other lineages. Gorilla events, but not events in other Great Apes, are strongly associated with a 15 bp motif commonly found in Alu sequences. This result is consistent with evolutionarily transient targeting of the motif by PRDM9, which induces double strand breaks and crossovers during meiosis at specific but rapidly changing sequence motifs. The motif is preferentially found in conversion recipients but not donors, and is substantially depleted in gorillas, consistent with loss of PRDM9 targets by meiotic drive. Recombination probability falls of exponentially with distance between loci, is reduced slightly by sequence divergence, and drops substantially with recipient divergence from the target motif. We identified 16 other high-copy motifs in human, often associated with transposable elements, with lineage-specific depletion and nearby gene conversion signatures, consistent with transient roles as PRDM9 targets. This work strengthens our understanding of recombination-mediated events in evolution and highlights the potential for interactions between PRDM9 and repetitive sequences to cause rapid change in the genome.