Egg-laying mammals (monotremes), represent the most basal extant mammalian lineage, and provide unique insight into mammalian evolution. In addition, monotremes have evolved sex chromosomes and a sex determination system independently from other mammals.
Doublesex and mab-3 related genes (DMRT genes) encode a family of transcription factors, that play central roles in the development of sex-specific differentiation across the metazoans. DMRT genes are characterised by the presence of a DNA binding DM domain, and are present in all metazoans, however the number of these genes varies between lineages. Therian mammals have 8 DMRT genes, with DMRT7 & DMRT8 reported as mammalian specific.
The most well characterised DMRT gene, DMRT1, functions as a sexual regulator universally in metazoans. In chicken DMRT1 is located on the Z sex chromosome and acts as a dosage dependent primary sex determination gene. In therian mammals DMRT1 is on an autosome but two copies are required for male development. Surprisingly in monotremes DMRT1 maps to the X specific region of platypus X5 which means that males have only one gene copy.
To gain insight into the evolution of DMRT genes in monotremes and other mammals we performed sequence and expression analysis. We identified DMRT1-7, but not DMRT8 in monotremes. Synteny supports the absence of DMRT8 in both monotremes, suggesting the evolution of DMRT8 coincides with the emergence of the therian sex chromosomes.
Monotremes are the only mammals where DMRT1 resides on a sex chromosome and no Y gametologue has been identified. In the platypus genome a single DMRT1 isoform is predicted but multiple isoforms are predicted for echidna DMRT1. RT-PCR and sequencing have confirmed the presence of multiple isoforms in both echidna and platypus. In addition, novel protein coding exons in monotreme DMRT1 have been identified, suggesting that monotreme DMRT1 has gone independent evolution in egg-laying mammals.