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

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. Many rearrangement hotspots are shared across species Recombination is a major mutational mechanism that has a crucial role in producing genetic diversity. Because of its potential impact on important phenotypes, including diseases, much attention has been paid to recombination, whether it is allelic or nonallelic Evolutionary approaches provide a means to investigate how these hotspots arose and have been maintained throughout evolution, which might enable us to better predict regions that affect the phenotype. A recent interesting finding is that most allelic recombination hotspots detected in the human genome do not exist in the chimpanzee genome, indicating a rapid turnover of hotspots The situation seems to be different for hotspots of nonallelic recombination, the major cause of genomic rearrangements such as duplications, deletions, and inversions. Recent studies of CNVs in various primate species have shown that CNV hotspots are often shared across species, even between human and macaqu