The avian Z-linked gene DMRT1 is required for male sex determination in the chicken

Abstract

Sex in birds is chromosomally based, as in mammals, but the sex chromosomes are different and the mechanism of avian sex determination has been a long-standing mystery. In the chicken and all other birds, the homogametic sex is male (ZZ) and the heterogametic sex is female (ZW). Two hypotheses have been proposed for the mechanism of avian sex determination. The W (female) chromosome may carry a dominant-acting ovary determinant. Alternatively, the dosage of a Z-linked gene may mediate sex determination, two doses being required for male development (ZZ). A strong candidate avian sex-determinant under the dosage hypothesis is the conserved Z-linked gene, DMRT1 (doublesex and mab-3-related transcription factor 1). Here we used RNA interference (RNAi) to knock down DMRT1 in early chicken embryos. Reduction of DMRT1 protein expression in ovo leads to feminization of the embryonic gonads in genetically male (ZZ) embryos. Affected males show partial sex reversal, characterized by feminization of the gonads. The feminized left gonad shows female-like histology, disorganized testis cords and a decline in the testicular marker, SOX9. The ovarian marker, aromatase, is ectopically activated. The feminized right gonad shows a more variable loss of DMRT1 and ectopic aromatase activation, suggesting differential sensitivity to DMRT1 between left and right gonads. Germ cells also show a female pattern of distribution in the feminized male gonads. These results indicate that DMRT1 is required for testis determination in the chicken. Our data support the Z dosage hypothesis for avian sex determination.

Did sex chromosome turnover promote divergence of the major mammal groups?

“…For instance, all birds have a ZZ male:ZW female system and share the same Z chromosome, determining sex by means of dosage of a Z‐borne gene DMRT1 25. Snakes, with a different ZW pair, also appear to be very stable, at least in the two families (Colubridae and Viperidae) with highly degraded W chromosomes 26.…”

No amicable divorce? Challenging the notion that sexual antagonism drives sex chromosome evolution

“…A single, Y-linked dominant gene DMY also determines sex in the medaka fish Oryzias latipes [96] but is absent from closely related species [97], indicating recent acquisition of a novel sex-determination system. In birds, the Z-linked gene DMRT1 forms a strong candidate for dosage-dependent single-gene sex determination [98], although the possibility that DMRT1 is regulated by upstream factors cannot be excluded.…”

Evolutionary history of two divergent Dmrt1 genes reveals two rounds of polyploidy origins in gibel carp

“…Several sex determination and sex chromosome-linked genes in vertebrates such as Dmy in medaka (Matsuda et al, 2002;Nanda et al, 2002), DM-W in the W chromosome of African clawed frog (Yoshimoto et al, 2008), and Dmrt1 in the Z chromosome of birds (Smith et al, 2009), have been shown to be recently duplicated homologs of Dmrt1. Because of the high evolutionary conservation and the newly recruited role in vertebrates (Herpin and Schartl, 2011;Xia et al, 2007), Dmrt1 also allows us to analyze the evolutionary history of genome duplication through examination of divergence and phylogeny of the duplicated genes.…”