Evolution of the Short Form of DNMT3A, DNMT3A2, Occurred in the Common Ancestor of Mammals

Genomic imprinting is found in marsupial and eutherian mammals, but not in monotremes. While the primary regulator of genomic imprinting in eutherians is differential DNA methylation between parental alleles, conserved imprinted genes in marsupials tend to lack DNA methylation at their promoters. DNA methylation at eutherian imprinted genes is mainly catalyzed by a DNA methyltransferase (DNMT) enzyme, DNMT3A. There are two isoforms of eutherian DNMT3A: DNMT3A and DNMT3A2. DNMT3A2 is the primary isoform for establishing DNA methylation at eutherian imprinted genes and is essential for eutherian genomic imprinting. In this study, we investigated whether DNMT3A2 is also present in the two other mammalian lineages, marsupials and monotremes. We identified DNMT3A2 in both marsupials and monotremes, although imprinting has not been identified in monotremes. By analyzing genomic sequences and transcriptome data across vertebrates, we concluded that the evolution of DNMT3A2 occurred in the common ancestor of mammals. In addition, DNMT3A/3A2 gene and protein expression during gametogenesis showed distinct sexual dimorphisms in a marsupial, the tammar wallaby, and this pattern coincided with the sex-specific DNA methylation reprogramming in this species as it does in mice. Our results show that DNMT3A2 is present in all mammalian groups and suggests that the basic DNMT3A/3A2-based DNA methylation mechanism is conserved at least in therian mammals.

Automated summary

Genomic imprinting is a common phenomenon in marsupial and eutherian mammals, but absent in monotremes. Differential DNA methylation is the primary mechanism for genomic imprinting in eutherians, while conserved imprinted genes in marsupials lack DNA methylation. This study investigates the presence of DNMT3A2, a DNA methyltransferase enzyme, in marsupials and monotremes, and identifies its presence in both lineages. Analysis of genomic sequences and transcriptome data suggests that DNMT3A2 evolved in the common ancestor of mammals. The study also reveals sexual dimorphism in DNMT3A/3A2 gene and protein expression during gametogenesis in a marsupial, indicating a conserved DNA methylation mechanism in therian mammals.