The marsupial imprinted gene MLH1 has retrocopies in three marsupial families

Background The mut-L homologue 1 gene (MLH1) is a DNA repair gene. Loss of biallelic expression of MLH1 in humans leads to increased predisposition to several cancer types. In the koala (Phascolarctos cinereus) and brushtail possum (Trichosurus vulpecula), MLH1 is imprinted, resulting in monoallelic parent-of-origin specific gene expression.Results Allele-specific methylation and expression analysis of MLH1 in tammar wallaby (Notamacropus (Macropus) eugenii) pouch young indicated MLH1 was maternally methylated and paternally expressed. A second site of MLH1 was identified, lacking introns. This site was a retrocopy, formed through the MLH1 mRNA incorporating into the tammar genome. An orthologous MLH1 retrocopy was identified in two macropodid marsupials and an additional two non-orthologous MLH1 retrocopies were identified in the bilby (Macrotis lagotis) and marsupial mole (Notoryctes typhlops). The tammar, bilby and marsupial mole MLH1 retrocopies had intact open reading frames and the tammar and bilby retrocopies were expressed. Protein structure alignment indicated the conformation of the 'parental' and retrocopy MLH1 protein may be conserved and therefore may have a comparable function to the parental MLH1 protein.Conclusions This second site of MLH1 expression may have introduced redundancy to MLH1 expression and compensate for silencing of the maternal MLH1 allele in marsupials.