The rise and fall of a human recombination hot spot

Human meiotic crossovers mainly cluster into narrow hot spots(1) that profoundly influence patterns of haplotype diversity(2) and that may also affect genome instability(3) and sequence evolution(4-6). Hot spots also seem to be ephemeral(7-9), but processes of hot-spot activation and their subsequent evolutionary dynamics remain unknown. We now analyze 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 y 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.