DNA methylation is a dynamic epigenetic modification found in most eukaryotic genomes. It is known to lead to a high CpG to TpG mutation rate. However, the relationship between the methylation dynamics in germline development and the germline mutation rate remains unexplored. In this study, we used whole genome bisulfite sequencing (WGBS) data of cells at 13 stages of human germline development and rare variants from the 1000 Genome Project as proxies for germline mutations to investigate the correlation between dynamic methylation levels and germline mutation rates at different scales. At the single-site level, we found a significant correlation between methylation and the germline point mutation rate at CpG sites during germline developmental stages. Then we explored the mutability of methylation dynamics in all stages. Our results also showed a broad correlation between the regional methylation level and the rate of C>T mutation at CpG sites in all genomic regions, especially in intronic regions; a similar link was also seen at all chromosomal levels. Our findings indicate that the dynamic DNA methylome during human germline development has a broader mutational impact than is commonly assumed.

BackgroundOlfactory receptors (ORs) can bind odor molecules and play a crucial role in odor sensation. Due to the frequent gains and losses of genes during evolution, the number of OR members varies greatly among different species. However, whether the extent of gene gains/losses varies between marine mammals and related terrestrial mammals has not been clarified, and the factors that might underlie these variations are unknown.ResultsTo address these questions, we identified more than 10,000 members of the OR family in 23 mammals and classified them into 830 orthologous gene groups (OGGs) and 281 singletons. Significant differences occurred in the number of OR repertoires and OGGs among different species. We found that all marine mammals had fewer OR genes than their related terrestrial lineages, with the fewest OR genes found in cetaceans, which may be closely related to olfactory degradation. ORs with more gene duplications or loss events tended to be under weaker purifying selection. The average gain and loss rates of OR genes in terrestrial mammals were higher than those of mammalian gene families, while the average gain and loss rates of OR genes in marine mammals were significantly lower and much higher than those of mammalian gene families, respectively. Additionally, we failed to detect any one-to-one orthologous genes in the focal species, suggesting that OR genes are not well conserved among marine mammals.ConclusionsMarine mammals have experienced large numbers of OR gene losses compared with their related terrestrial lineages, which may result from the frequent birth-and-death evolution under varied functional constrains. Due to their independent degeneration, OR genes present in each lineage are not well conserved among marine mammals. Our study provides a basis for future research on the olfactory receptor function in mammals from the perspective of evolutionary trajectories.

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