Corrigendum: Evolutionary expansion of DNA hypomethylation in the mammalian germline genome

Abstract

Corrigendum: Evolutionary expansion of DNA hypomethylation in the mammalian germline genome

High prevalence of Prdm9-independent recombination hotspots in placental mammals

“…This shows that many MDH loci are specifically hypomethylated in mice but not in dogs. This is consistent with previous observations showing that murid genomes have accumulated many new HMRs compared to other mammals (Qu et al, 2018). To test whether these shifts in methylation levels are associated with changes in recombination activity, we computed the LD-based recombination rate in dogs as a function of the distance to the closest MDH locus, separating those whose midpoints overlap a HMR in dogs (7,186), and those that do not (7,283)(Fig.…”

“…Indeed, indirect evidences suggested that recombination hotspots in dogs are associated to germline hypomethylated regions (HMRs) (Berglund et al, 2015). Using HMRs identified by bi-sulfite sequencing in dog sperm (Qu et al, 2018), we observed that 74% of dog hotspots are located inside HMRs, which represent only 3.7% of the dog genome. In mice, the overlap is even stronger: using HMRs identified in mouse sperm (Hammoud et al, 2014), we observed that out of the 30,929 hotspots found in the Prdm9 / mutant, 93% are located within HMRs, which cover only 4.6% of the mouse genome (see methods for details).…”

“…We showed that the activity of those Prdm9-independent hotspots is highly dependent on DNA hypomethylation. This implies that despite a general conservation, Prdm9-independent recombination hotspots are evolving slowly, in concert with germline DNA hypomethylation (Qu et al, 2018;Berglund et al, 2015).…”

“…We excluded hotspots that were High prevalence of Prdm9-independent recombination hotspots in placental mammals larger than 20 kb as they do not fit the definition of hotspots. Data sets of hypomethylated regions in mouse and dog sperm (identified using Bi-sulfite sequencing) were retrieved from the literature (Hammoud et al, 2014;Qu et al, 2018). Even though methylation data on spermatocytes would have been more fit for the task at hand, only sperm is available in the literature for dogs.…”

“…Using this approach, we calculated the percentage of the genome covered by the hotspots by multiplying the number of hotspots by 5,000, and dividing by the assembly size. For the overlap with HMRs we defined hotspots as the 5 kb windows centered on their midpoint and kept the size of HMRs defined in the study of Qu et al 2018(Qu et al, 2018. The percentage of the genome covered by HMRs was computed as the sum of all HMR sizes divided by the assembly size.…”