An SRY-related sequence on the marsupial X chromosome:implications for the evolution of the mammalian testis-determininggene.

Abstract

The (9). The relationships between the SR Y and SOX genes are obviously of interest in considering the origin and evolution of the SRY gene in mammals.Marsupials diverged from eutherian (placental) mammals 120-150 million years ago and monotremes (egg-laying mammals) diverged even earlier, so that comparisons between these three major mammalian groups may provide information about the function and early evolution of mammalian sex chromosomes and sex-determining genes. Eutherian, marsupial, and monotreme sex chromosomes have been found to differ in size and gene content, enabling the different evolutionary origins of regions of the human sex chromosomes to be deduced. The genes on the long arm and proximal short arm of the human X chromosome are present on the X chromosome in marsupial and monotreme mammals, and this region, therefore, represents a conserved, probably original, mammalian X chromosome (10,11). The marsupial and monotreme X chromosome lacks genes borne on the short arm of the human X chromosome, suggesting that this region was originally autosomal and was added later to the eutherian X chromosome. The presence of several genes in this region with homologues on the Y chromosome implies that the region was added to both X and Y chromosomes, probably by recombination within an original pseudoautosomal region (10,12). In marsupials, as in eutherian mammals, the Y chromosome is testis determining, but at least some sexual dimorphisms are sex hormone independent and seem to be a function of X chromosome dosage, rather than the presence or absence of a Y chromosome (13).We have isolated an SR Y-related sequence from the marsupial X chromosome, which is closely homologous to the mouse and human SOX3 gene. This raises the possibility that X chromosome inactivation or gene dosage may play a role in sex determination in marsupials. However, we suggest that a more likely explanation for the presence of SR Y homologues on marsupial, mouse, and human X chromosomes is that SOX3 and SRY were originally alleles of a developmentally important gene shared by partly differentiated ancestral X and Y chromosomes. MATERIALS AND METHODSWe used two marsupial species, representing the two major Australian orders that diverged about 50 million years ago, the striped-faced dunnart Sminthopsis macroura (Order Polyprotodonta, Family Dasyuridae) and the Tammar wallaby Macropus eugenii (Order Diprotodonta, Family Macropodidae). Tissue was originally provided by

Co-option of Sox3 as the male-determining factor on the Y chromosome in the fish Oryzias dancena

“…This suggests that the new Y chromosome of O. dancena arose by co-option of the Sox3 gene. A similar evolutionary process is thought to have occurred in mammals, in which the male-determining gene, Sry is considered to have evolved from Sox3 through a regulatory mutation in the proto-Y chromosome allele 7 . This hypothesis has been strongly supported by recent studies of Sox3 transgenic mice and human sex reversal cases.…”

“…Most experimental studies of primary genetic signals in vertebrates have been performed in welldeveloped model taxa having sex chromosomes. For example, the Y chromosome gene, Sry, is the master initiator for testicular development in mouse and human [4][5][6] , and is considered to have evolved from the X chromosomal Sox3 gene as an allelic variant on a proto-Y chromosome in the therian mammalian lineage 7,8 . However, Sry-or Sox3-dependent sex determination has not been found in other vertebrates.…”

Did sex chromosome turnover promote divergence of the major mammal groups?

“…2). SRY is thought to have evolved from SOX3 , a highly conserved gene that lies on the X in mammals 44 and is expressed in the central nervous system and germcells, but not the somatic cells of the testis, where the sex determining message must be received 45. Mis‐expression of SOX3 in the Sertoli cells causes sex reversal in humans and mice 46, suggesting that a change in tissue of expression, perhaps by fusion with a gonad‐specific promotor, created the male‐dominant SRY gene that took over sex determination from the ancestral gene 47.…”

Testis development in the absence of SRY: chromosomal rearrangements at SOX9 and SOX3

“…SOX3, encoding a protein very similar to SRY, might be the ancestral SOX gene from which the SRY gene was derived. 35 Duplications involving SOX3 and deletions of its 5′ region (Figure 1d) have been reported in at least four cases of XX DSD. 16,17 Moreover, a mouse model in which SOX3 is ectopically expressed in the developing gonads shows complete XX sex reversal, suggesting that gain-of-function mutations of SOX3 might act as an SRY surrogate in sex determination, promoting SOX9 gonadal expression.…”