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

HATTORI, R.S.; MARAI, Y.; OURA, M.; MASUDA, S.; MAJHI, S.K.; SAKAMOTO, T.; FERNANDINO, J.I.; SOMOZA, G.M.; YOKOTA, M.; STRÜSSMANN, C.A.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Año: 2012 vol. 109 p. 2955 - 2959

0027-8424

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, andDMRT1 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 earlierthan 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.