A Tandem Duplicate of Anti-Müllerian Hormone with a Missense SNP on the Y Chromosome Is Essential for Male Sex Determination in Nile Tilapia, Oreochromis niloticus

By Li, Minghui, Y. Sun, J. Zhao, H. Shi, S. Zeng, K. Ye, D. Jiang, L. Zhou, L. Sun, W. Tao, Y. Nagahama, T.D. Kocher, D. Wang

Plos One, 11(11):e1005678 20-Nov-2015. DOI: 10.1371/journal.pgen.1005678


" Variation in the TGF-ß signaling pathway is emerging as an important mechanism by which gonadal sex determination is controlled in teleosts. Here we show that amhy, a Y-specific duplicate of the anti-Müllerian hormone (amh) gene, induces male sex determination in Nile tilapia. amhy is a tandem duplicate located immediately downstream of amhDelta-y on the Y chromosome. The coding sequence of amhy was identical to the X-linked amh (amh) except a missense SNP (C/T) which changes an amino acid (Ser/Leu92) in the N-terminal region. amhy lacks 5608 bp of promoter sequence that is found in the X-linked amh homolog. The amhDelta-y contains several insertions and deletions in the promoter region, and even a 5 bp insertion in exonVI that results in a premature stop codon and thus a truncated protein product lacking the TGF-ß binding domain. Both amhy and amhDelta-y expression is restricted to XY gonads from 5 days after hatching (dah) onwards. CRISPR/Cas9 knockout of amhy in XY fish resulted in male to female sex reversal, while mutation of amh?-y alone could not. In contrast, overexpression of Amhy in XX fish, using a fosmid transgene that carries the amhy/amhDelta-y haplotype or a vector containing amhy ORF under the control of CMV promoter, resulted in female to male sex reversal, while overexpression of AmhDelta-y alone in XX fish could not. Knockout of the anti-Müllerian hormone receptor type II (amhrII) in XY fish also resulted in 100% complete male to female sex reversal. Taken together, these results strongly suggest that the duplicated amhy with a missense SNP is the candidate sex determining gene and amhy/amhrII signal is essential for male sex determination in Nile tilapia. These findings highlight the conserved roles of TGF-ß signaling pathway in fish sex determination "

Classification: Genes and genetics, Africa.

Language: English

Li, Minghui & Y. Sun, J. Zhao, H. Shi, S. Zeng, K. Ye, D. Jiang, L. Zhou, L. Sun, W. Tao, Y. Nagahama, T.D. Kocher, D. Wang. 2015. "A Tandem Duplicate of Anti-Müllerian Hormone with a Missense SNP on the Y Chromosome Is Essential for Male Sex Determination in Nile Tilapia, Oreochromis niloticus". Plos One. 11(11):e1005678. DOI: 10.1371/journal.pgen.1005678 (crc07006) (abstract)