%0 Journal Article %T A Tandem Duplicate of Anti-M¨¹llerian Hormone with a Missense SNP on the Y Chromosome Is Essential for Male Sex Determination in Nile Tilapia, Oreochromis niloticus %A Minghui Li  %A Yunlv Sun  %A Jiue Zhao  %A Hongjuan Shi  %A Sheng Zeng  %A Kai Ye  %A Dongneng Jiang  %A Linyan Zhou  %A Lina Sun  %A Wenjing Tao %J PLOS Genetics %D 2015 %I Public Library of Science (PLoS) %R 10.1371/journal.pgen.1005678 %X Variation in the TGF-¦Â 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-M¨¹llerian hormone (amh) gene, induces male sex determination in Nile tilapia. amhy is a tandem duplicate located immediately downstream of amh¦¤-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 amh¦¤-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-¦Â binding domain. Both amhy and amh¦¤-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/amh¦¤-y haplotype or a vector containing amhy ORF under the control of CMV promoter, resulted in female to male sex reversal, while overexpression of Amh¦¤-y alone in XX fish could not. Knockout of the anti-M¨¹llerian 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-¦Â signaling pathway in fish sex determination. %U http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1005678