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The rise and fall of a human recombination hot spot

Abstract

Human meiotic crossovers mainly cluster into narrow hot spots1 that profoundly influence patterns of haplotype diversity2 and that may also affect genome instability3 and sequence evolution4,5,6. Hot spots also seem to be ephemeral7,8,9, 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.

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Figure 1: Identification of a sperm crossover hot spot from family linkage maps.
Figure 2: Variation between men in sperm crossover activity and biased gene conversion.
Figure 3: Active and suppressed haplotypes at hot-spot S2.
Figure 4: Evolutionary dynamics of hot-spot S2.

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Acknowledgements

We thank J. Blower and volunteers for providing semen samples, T.E. King and P. Balaresque for DNA samples, A. Webb for bioinformatics support, colleagues for helpful discussions, and the Medical Research Council, the Wellcome Trust (ref. 081227/Z/06/Z), the Royal Society and the Louis-Jeantet Foundation for funding support.

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A.J.J. and R.N. designed the study and performed the analyses, and A.J.J. wrote the paper.

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Correspondence to Alec J Jeffreys.

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Jeffreys, A., Neumann, R. The rise and fall of a human recombination hot spot. Nat Genet 41, 625–629 (2009). https://doi.org/10.1038/ng.346

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