The rise and fall of a human recombination hot spot

Human meiotic crossovers mainly cluster into narrow hot spots1 that profoundly influence patterns of haplotype diversity2 and which may also impact on genome instability3 and sequence evolution4-6. Hot spots also appear to be ephemeral7-9 but processes of hot-spot activation and their subsequent evolutionary dynamics remain unknown. We now analyse the life cycle of a recombination hot spot. Sperm typing revealed a polymorphic hot spot that was activated in cis by a single base change, providing evidence for a primary sequence determinant necessary, though not sufficient, to activate recombination. This activating mutation occurred roughly 70,000 years ago and has persisted to the present, most likely fortuitously through genetic drift despite its systematic elimination by biased gene conversion. Nonetheless, this self-destructive conversion will eventually lead to hot-spot extinction. These findings define a subclass of highly transient hot spots and highlight the importance of understanding hot-spot turnover and how it influences haplotype diversity.