Evolution of the vertebrate DNMT3 gene family: a possible link between existence of <i>DNMT3L</i> and genomic imprinting

Abstract

DNA methylation plays an essential role in genomic imprinting observed in eutherian mammals and marsupials. In mouse, one of the two de novo DNA methyltransferases, Dnmt3a, and a related protein, Dnmt3L have been shown to be essential for imprint establishment in the parental germline. To gain insights into the evolution of imprinting mechanisms, we have identified and characterized the DNMT3 family genes in other vertebrate species. We cloned cDNAs for chicken DNMT3A and DNMT3B, whose putative protein products shared 81.5% and 48.6% amino acid sequence identity with their mouse orthologues. Using computer-assisted database searches, we also identified DNMT3A and DNMT3B orthologues in fish (fugu and zebrafish) and marsupials (opossum). We found that, while opossums had an orthologue for DNMT3L, chickens and fish did not have this gene. Thus, unlike the other DNMT3 members, DNMT3L was restricted to the species in which imprinting occurs. The acquisition of DNMT3L by a common ancestor of eutherians and marsupials might have been closely related to the evolution of imprinting.

Transposable elements in the mammalian germline: a comfortable niche or a deadly trap?

“…Although catalytically inactive, biochemical assays have revealed that Dnmt3L facilitates de novo methylation by stabilizing the active conformation of Dnmt3A, this therefore allows a more efficient transfer of methyl groups onto target sequences (Chedin et al, 2002;Jia et al, 2007). It should be noted that Dnmt3L is not only functionally but also evolutionarily linked to the protection of the germline against TEs: Dnmt3L specifically emerged in eutherian mammals, some 150 million years ago, coinciding with an important TE expansion in mammalian genomes (Yokomine et al, 2006;Warren et al, 2008).…”

Plasticity in Dnmt3L-dependent and -independent modes of de novo methylation in the developing mouse embryo

“…Whereas Dnmt3a and Dnmt3b orthologs are found widely among distant eukaryotic species, a third Dnmt3 member, Dnmt3-like (Dnmt3l), has evolved uniquely in mammals (Yokomine et al, 2006). This gene encodes a catalytically inert protein that is unable to methylate DNA substrates alone but serves as a regulator of the de novo methylation machinery.…”

DNA Methylation in Mammalian and Non-Mammalian Organisms

“…The chicken genome contains homologues of each mammalian DNMT (Table 1) with the exception of DNMT3L (Yokomine et al, 2006) each having high conservation with mammalian proteins; with DNMT1 having 94% identical amino acid sequence (Tajima et al, 1995).…”