Mutational bias in spermatogonia impacts human regulatory sites

Vera’s analysis of spermatogonial ATAC-seq data from Martin Taylor’s lab is now available (biorxiv; tweetorial) and shows that spermatogonial regulatory sites that are bound by particular factors (such as NRF1) are associated with higher mutation rates. Human populations show enrichment for singleton (ie relatively recent) deletion breakpoints at these sites. Surprisingly the same sites are also enriched for short insertions, and these insertions often duplicate the binding sites of the factors binding there, producing clusters of binding sites. As a side effect, when other cells/tissues that share regulatory sites with spermatogonia (such as regions of the developing brain) they are also impacted by these enrichments of mutations – suggesting that there may be a cost of spermatogonial mutational bias in causing disruptions to human development.