Importantly, we reveal that DNMT3C is composed of two independently evolving segments: the latter two-thirds have undergone recurrent gene conversion with Dnmt3B, whereas the N-terminus has instead evolved under strong diversifying selection. Using a phylogenomic approach, we confirm here that Dnmt3C arose through a single duplication of Dnmt3B that occurred ∼60 Ma in the last common ancestor of muroid rodents. The evolutionary forces that shaped DNMT3C’s unique function are unknown. However, many rodent species deploy a third enzyme, DNMT3C, to selectively methylate the promoters of young retrotransposon insertions in their germline. During germ cell development, most mammalian species utilize the de novo DNA methyltransferases DNMT3A and DNMT3B to establish DNA methylation patterns. Transcriptional silencing of retrotransposons via DNA methylation is paramount for mammalian fertility and reproductive fitness.
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