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Abstract

Meiotic recombination ensures the correct segregation of homologous chromosomes during gamete formation and
contributes to DNA diversity through both large-scale reciprocal crossovers and very localised gene conversion events, also
known as noncrossovers. Considerable progress has been made in understanding factors such as PRDM9 and SNP variants
that influence the initiation of recombination at human hotspots but very little is known about factors acting downstream.
To address this, we simultaneously analysed both types of recombinant molecule in sperm DNA at six highly active
hotspots, and looked for disparity in the transmission of allelic variants indicative of any cis-acting influences. At two of the
hotspots we identified a novel form of biased transmission that was exclusive to the noncrossover class of recombinant, and
which presumably arises through differences between crossovers and noncrossovers in heteroduplex formation and biased
mismatch repair. This form of biased gene conversion is not predicted to influence hotspot activity as previously noted for
SNPs that affect recombination initiation, but does constitute a powerful and previously undetected source of
recombination-driven meiotic drive that by extrapolation may affect thousands of recombination hotspots throughout
the human genome. Intriguingly, at both of the hotspots described here, this drive favours strong (G/C) over weak (A/T)
base pairs as might be predicted from the well-established correlations between high GC content and recombination
activity in mammalian genomes.