A Y-linked anti-Müllerian hormone duplication takes over a critical role in sex determination

TLDR

Gonadal sex determination in vertebrates follows a genetically programmed sequence, with known master genes such as SRY, DMY, DM‑W, and DMRT1 encoding transcription factors. The duplicated amh copy, amhy, resides on the Y chromosome, is expressed early (6 days post‑fertilization versus 12 weeks for autosomal amh), and localizes to presumptive Sertoli cells during XY testicular differentiation. Knocking down amhy in XY embryos up‑regulates foxl2 and cyp19a1a, induces ovary development, and supports its role as the master sex‑determining gene—a unique hormone‑based example in vertebrates.

Abstract

Gonadal sex determination in vertebrates generally follows a sequence of genetically programmed events. In what is seemingly becoming a pattern, all confirmed or current candidate “master” sex-determining genes reported in this group, e.g., SRY in eutherian mammals, DMY/dmrt1bY in medaka, DM-W in the African clawed frog, and DMRT1 in chicken encode transcription factors. In contrast, here we show that a male-specific, duplicated copy of the anti-Müllerian hormone ( amh ) is implicated in testicular development of the teleost fish Patagonian pejerrey ( Odontesthes hatcheri ) . The gene, termed amhy because it is found in a single metacentric/submetacentric chromosome of XY individuals, is expressed much earlier than the autosomal amh (6 d after fertilization vs. 12 wk after fertilization) and is localized to presumptive Sertoli cells of XY males during testicular differentiation. Moreover, amhy knockdown in XY embryos resulted in the up-regulation of foxl2 and cyp19a1a mRNAs and the development of ovaries. These results are evidence of a functional amh duplication in vertebrates and suggest that amhy may be the master sex-determining gene in this species. If confirmed, this would be a unique instance of a hormone-related gene, a member of the TGF-β superfamily, in such a role.