Xiphophorus maculatus

Evolution of sex determination in vertebrates: the model Xiphophorus

The molecular basis of sex determination and gonad differentiation is poorly understood in non-mammalian vertebrates, and even in human important members of the sex-determining cascade are still to be identified. The Y-chromosomal gene Sry, inducing the male phenotype in human and mouse, has been formed during the evolution of mammals and is absent from other vertebrate lineages. The mammalian Y chromosome is losing its genes; this ongoing process might lead to the loss of the Y chromosome and to the extinction of Homo sapiens. Investigation of sex determination mechanisms in non-mammalian vertebrate models might help to predict the future of sex determination in human and to discover alternative sex-determining systems able to substitute for the current Sry-dependent pathway.

Fish are attractive models to study sex determination, particularly because they have developed an amazing diversity of environmental and genetic strategies to establish sexual dimorphism. No simple model of genetic sex determination can be generalized in fish. Both male (XX/XY) and female heterogamety (ZZ/ZW) has been observed, as well as more complicated situations involving multiple sex chromosomes, polygenic sex determination and autosomal modifiers. Furthermore, gonadal sex differentiation can be strongly influenced in some fishes by environmental factors including temperature, pH or fish density. Sex inversion can be obtained in several fish species spontaneously or after treatment by steroid hormones. Almost nothing is known about the molecular and evolutionary mechanisms driving the variability of sex determination. This phenomenon might play a role in speciation in fish.

Fig3.: Genes and gene loci linked to the master sex-determining gene SD on the sex chromosomes of the platyfish Xiphophorus maculatus.

Importantly, molecular sexing and manipulation of sex determination in fish are key economical challenges for the aquaculture. The necessity of the control of reproduction to avoid overcrowding, as well as the presence of sex-specific differences in fish growth, quality and behavior make monosex populations generally highly desirable in fish farming (all-male or all-female populations, depending on the species). Monosex populations can be generated after treatment of one of the parents with estrogens or androgens. The development of molecular tests to determine routinely the sex of individuals at early stages of development could allow the early selection of breeders of a chosen genotype necessary for the production of such monosex populations, and the rapid analysis of products in breeding, androgenesis and gynogenesis experiments.

Almost no information is available concerning sex determination mechanisms in most fishes, and neither sex-linked molecular markers nor sex chromosomes are identifiable in the classical fish models, the zebrafish Danio rerio and the pufferfishes Takifugu rubripes (Fugu) and Tetraodon nigroviridis. The master sex-determining gene dmrt1bY of the medaka Oryzias latipes is present only in a very restricted number of species, and is therefore not the ubiquitous sex-determining gene in fish (Matsuda et al. 2002, Nature 417:559; Nanda et al. 2002, Proc Natl Acad Sci USA 2002, 99:11778). Therefore, alternative models are needed to identify the master sex-determining gene(s) in more than 23.000 fish species.

The platyfish Xiphophorus maculatus is an ideal model to perform the positional cloning of a master sex-determining (SD) gene. In this fish, SD is located between two genes, the melanoma-inducing oncogene Xmrk and its proto-oncogenic duplicate egfrb, which are both already characterized at the molecular level. This situation should allow the identification of the master sex-determining gene of the platyfish by a positional cloning strategy. SD is also closely linked to loci involved in pigmentation and/or melanoma phenotype (Mdl and RY, for “red-yellow” locus) and in the onset of sexual maturity (P, for “puberty”) (Fig. 3). The identification of these genetic loci, also aim of the project, is highly relevant for both cancer research and aquaculture.

Definition of Xiphophorus according to Pierre Desproges (in French)

Xiphophore (n.m.): Le xiphophore est un petit poisson de coloration variée, de six à dix centimètres de long et originaire du Mexique. Au moment de se reproduire, le xiphophore émet un cri strident: Christiane! pour appeler la xiphophorette qui accourt bientôt ventre à flotte, la caudale en feu. S’ensuit alors une danse d’amour effrénée dont le tendre spectacle ne peut que toucher le cœur de tout homme capable de supporter un documentaire écologique marin sans balancer ensuite une grenade offensive dans le lac d’Enghien (Dictionnaire superflu à l’usage de l’élite et des bien nantis, 1985).