Evidence for evolutionary conservation of sex-determining genes

Abstract

Most metazoans occur as two sexes. Surprisingly, molecular analyses have hitherto indicated that sex-determining mechanisms differ completely between phyla. Here we present evidence to the contrary. We have isolated the male sexual regulatory gene mab-3 from the nematode Caenorhabditis elegans and found that it is related to the Drosophila melanogaster sexual regulatory gene doublesex (dsx)2. Both genes encode proteins with a DNA-binding motif that we have named the 'DM domain'. Both genes control sex-specific neuroblast differentiation and yolk protein gene transcription; dsx controls other sexually dimorphic features as well. The form of DSX that is found in males can direct male-specific neuroblast differentiation in C. elegans. This structural and functional similarity between phyla suggests a common evolutionary origin of at least some aspects of sexual regulation. We have identified a human gene, DMT1, that encodes a protein with a DM domain and find that DMT1 is expressed only in testis. DMT1 maps to the distal short arm of chromosome 9, a location implicated in human XY sex reversal. Proteins with DM domains may therefore also regulate sexual development in mammals.

Genetic basis of male sexual behavior

“…Consistent with the hypothesis that DM proteins have an ancient role in sexual differentiation, vertebrates also contain these genes, at least some of which have been documented to play a role in development of the male (Raymond et al, 1998). DM family gene expression has been detected in the testes of all vertebrates examined (Zarkower, 2001).…”

“…These genes are members of the DM-domain transcription factor family and are required for multiple diverse aspects of male development in worms, flies, and vertebrates (Raymond et al, 1998(Raymond et al, , 2000Zarkower, 2001;Matsuda et al, 2002). Their conservation across phyla in both structure and function is in contrast to the nonconservation of genes upstream of them in the sex-determination hierarchy (Hodgkin, 1992;Wilkins, 1995;Marín and Baker, 1998).…”

“…3). DSX M and MAB-3 have some regulatory targets in common, namely the genes for yolk proteins, which they repress in the male, and DSX M can substitute for MAB-3 in directing aspects of C. elegans male development (Raymond et al, 1998;Yi and Zarkower, 1999). This supports the view that these genes are descended from a common primordial sex-determination gene.…”

Sexual dimorphic expression of DMRT1 and Sox9a during gonadal differentiation and hormone‐induced sex reversal in the teleost fish Nile tilapia (Oreochromis niloticus)

“…One of these genes, the doublesex/mab-3 conserved domain (DM) domain-containing gene (DMRT1; doublesex/mab-3 related transcription factor-1), has been found in mammals, a bird species, a reptile species, a frog species, teleosts, nematodes, and flies (Shen and Hodgkin, 1988;Coschigano and Wensink, 1993;Raymond et al, 1998Raymond et al, , 1999Smith et al, 1999;De Grandi et al, 2000;Kettlewell et al, 2000;Guan et al, 2000;Marchand et al, 2000;Shibata et al, 2002). The DM domain, a zinc fingerlike DNA-binding motif (Erdman and Burtis, 1993;Raymond et al, 1998), was first identified in the sexual regulatory proteins Drosophila doublesex and C. elegans mab-3 and is widely conserved among metazoans. DMRT1 appears to be involved in a certain type of XY sex reversal in humans (Bennet et al, 1993;Flejter et al, 1998;Yi et al, 2000;Veitia et al, 2001).…”

Characterization of Bovidae sex-determining gene SRY

“…(3) Our recent finding suggests that the X chromosome occurred much earlier at about 440 Mya when fish appeared (Yi et al, unpublished data). Finally (4) another sex-determining gene DMRT1 is conserved among humans, chickens, nematodes and flies [16], suggesting that at least some aspects of sexual regulation have a common evolutionary origin.…”