Molecular evolution of DNMT1 in vertebrates: duplications in marsupials followed by positive selection

Abstract

DNA methylation is mediated by a conserved family of DNA methyltransferases (Dnmts). The human genome encodes five Dnmts: Dnmt1, Dnmt2, Dnmt3a, Dnmt3b and Dnmt3L. Despite their high degree of conservation among different species, genes encoding Dnmts have been duplicated and/or lost in multiple lineages throughout evolution, indicating that the DNA methylation machinery has some potential to undergo evolutionary change. However, little is known about the extent to which this machinery, or the methylome, varies among vertebrates. Here, we study the molecular evolution of Dnmt1, the enzyme responsible for maintenance of DNA methylation patterns after replication, in 79 vertebrate species. Our analyses show that all studied species exhibit a single copy of DNMT1, with the exception of tilapia and marsupials (tammar wallaby, koala, Tasmanian devil and opossum), each of which exhibits two apparently functional DNMT1 copies. Our phylogenetic analyses indicate that DNMT1 duplicated before the divergence of marsupials (i.e., at least ~75 million years ago), thus giving rise to two DNMT1 copies in marsupials (copy 1 and copy 2). In the opossum lineage, copy 2 was lost, and copy 1 recently duplicated again, generating three DNMT1 copies: two putatively functional genes (copy 1a and 1b) and one pseudogene (copy 1{psi}). Both marsupial copies (DNMT1 copies 1 and 2) are under purifying selection, and copy 2 exhibits elevated rates of evolution and signatures of positive selection, suggesting a scenario of neofunctionalization. This gene duplication might have resulted in modifications in marsupial methylomes and their dynamics.