No equivalent to the mammalian Sry sex-determining gene has been found in non-mammalian vertebrates. In an Advanced Online Publication in Nature, Masaru Matsuda and colleagues describe the characterization of the first fish gene required for male development (Nature 2002, DOI://10.1038/nature751).

Matsuda et al. chose the medaka fish (Oryzias latipes), a cousin of the zebrafish that is widely used a genetic model organism to study vertebrate development. The major difference between the medaka Y and X chromosomes is thought to be the sex-determining region. They used a Y congenic strain and a positional cloning approach to narrow down the sex-determining region to a 530 kb region that includes 52 predicted genes. Study of an XY female with a large deletion of the Y chromosome allowed them to narrow the search further, to a 250 kb region with 27 predicted genes. They tested each of these candidates and found just one (which they named DMY) that is expressed exclusively in XY embryos.

DMY encodes a 267 residue protein that has a conserved DM domain with a DNA-binding motif. Matsuda et al. found two XY females with distinct mutations in DMY (one is a loss-of-function mutation and the other is a depressed expression mutant), confirming the importance of DMY in sex determination. DMY is expressed in XY embryos but not XX embryos and is expressed in somatic cells surrounding the germ cells. DMY is homologous to the DMRT1 (DM-related transcription factor 1) protein that is also implicated in mammalian testis differentiation. These results suggest that DMY plays a pivotal role in testicular differentiation and sex determination in fish.