Extended Data Fig. 7. Phylogeny and expression of DNMT3 enzymes.

(a) Maximum likelihood phylogenetic tree of DNMT3 orthologues across animals, representing the full version of that presented in Figure 4a. Nodal supports represent 100 bootstrap nonparametric replications. Schematic protein domain configurations shown for each clade. PWWP, Pro-Trp-Trp-Pro motif domain (PF00855). AAD ATRX, DNMT3, DNMT3L domain. MT, cytosine Methyltransferase domain (PF00145). CH, Calponin Homology domain (PF00307). Asterisk highlights arctic lamprey sequences. Broken domains indicate that the domain has large deletions in the given clade. (b) Table with the steady-state transcriptional level of DNMT3A in vertebrate samples, and DNMT3 in invertebrate samples. Compared to previous analysis of the DNMT3 family, here we describe for the first time the presence of DNMT3L in non-mammalian genomes. These include non-avian reptiles (turtles, crocodiles and squamates) and two lamprey genomes. This indicates that DNMT3L was one of the ancestral onhologues product of the vertebrate ancestral WGD. Interestingly, both lampreys and tetrapod sequences show a truncated cytosine methyltransferase domain, which might indicate that the DNMT3L has been conserved despite its lack of catalytic activity.