title: The human sex-reversing ATRX gene has a homologue on the marsupial Y chromosome, ATRY: implications for the evolution of mammalian sex determination.
abstract: Mutations in the ATRX gene on the human X chromosome cause X-linked alpha-thalassemia and mental retardation. XY patients with deletions or mutations in this gene display varying degrees of sex reversal, implicating ATRX in the development of the human testis. To explore further the role of ATRX in mammalian sex differentiation, the homologous gene was cloned and characterized in a marsupial. Surprisingly, active homologues of ATRX were detected on the marsupial Y as well as the X chromosome. The Y-borne copy (ATRY) displays testis-specific expression. This, as well as the sex reversal of ATRX patients, suggests that ATRY is involved in testis development in marsupials and may represent an ancestral testis-determining mechanism that predated the evolution of SRY as the primary mammalian male sex-determining gene. There is no evidence for a Y-borne ATRX homologue in mouse or human, implying that this gene has been lost in eutherians and its role supplanted by the evolution of SRY from SOX3 as the dominant determiner of male differentiation.
authors.affiliation: Department of Genetics and Evolution, La Trobe University, Melbourne 3083, Australia. a.pask@zoology.unimelb.edu.au
authors.forename: A
authors.initials: A
authors.lastname: Pask
authors.forename: M B
authors.initials: MB
authors.lastname: Renfree
authors.forename: J A
authors.initials: JA
authors.lastname: Marshall Graves
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D012734:Disorders of Sex Development; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007614:Macropodidae / Q000235:genetics*; D008297:Male; D008322:Mammals / Q000235:genetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D019849:Sex Determination Processes; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D014960:X Chromosome; D000075924:X-linked Nuclear Protein; D014998:Y Chromosome
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; C092332:ATRX protein, human; C490462:Atrx protein, mouse; D000075924:X-linked Nuclear Protein