Although the sex-determining gene
Sry has been identified in mammals, no comparable genes have been found in non-mammalian vertebrates. To clone positionally the sex-determining region of the medaka,
Oryzias latipes, we generated a Y congenic strain to highlight the genetic differences between the X and Y chromosomes from inbred strains of medaka. We used recombinant breakpoint analysis and deletion analysis of the Y chromosome of a congenic XY female to restrict the sex-determining region to 250-kb stretch of the Y chromosome. Shotgun sequencing of this region predicted 27 genes. Three of these genes were expressed during sexual differentiation. However, only one gene was Y specific. The full-length cDNA sequence of this gene encodes a putative protein of 267 amino acids, including the highly conserved DM domain. We thus named it
DMY. To establish a role for
DMY during sexual differentiation, we screened wild medaka populations for naturally occurring
DMY mutants. Two XY females with distinct mutations in
DMY were found in separate populations. The first heritable mutant – a single insertion in exon 3 and the subsequent truncation of DMY – resulted in all XY female offspring. Similarly, the second XY mutant female showed reduced
DMY expression with a high proportion of XY female offspring. Furthermore, during normal development,
DMY is expressed only in somatic cells of XY gonads. These findings strongly suggest that the sex-specific
DMY is required for normal testicular development and is a prime candidate for the medaka sex-determining gene.
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