The role of gene conversion in preserving rearrangement hotspots in the human genome

•Many hotspots of nonallelic homologous recombination (NAHR) are shared across primates.•Segmental duplications can engage in NAHR for tens of millions of years when gene conversion is occurring.•Gene conversion has been having an important role in preserving NAHR hotspots associated with common copy number variants (CNVs) and also with rare CNVs linked to genomic disorders.

Hotspots of non-allelic homologous recombination (NAHR) have a crucial role in creating genetic diversity and are also associated with dozens of genomic disorders. Recent studies suggest that many human NAHR hotspots have been preserved throughout the evolution of primates. NAHR hotspots are likely to remain active as long as the segmental duplications (SDs) promoting NAHR retain sufficient similarity. Here, we propose an evolutionary model of SDs that incorporates the effect of gene conversion and compare it with a null model that assumes SDs evolve independently without gene conversion. The gene conversion model predicts a much longer lifespan of NAHR hotspots compared with the null model. We show that the literature on copy number variants (CNVs) and genomic disorders, and also the results of additional analysis of CNVs, are all more consistent with the gene conversion model.