The human sex-reversing ATRX gene has a homologue on the marsupial Y chromosome, ATRY: Implications for the evolution of mammalian sex determination

The human sex-reversing ATRX gene has a homologue on the marsupial Y chromosome, ATRY: Implications for the evolution of mammalian sex determination

^*Department of Genetics and Evolution, La Trobe University, Melbourne 3083, Australia; and ^‡Department of Zoology, The University of Melbourne, Melbourne 3010, Australia

Communicated by Neal L. First, University of Wisconsin, Madison, WI (received for review July 13, 1999)

Abstract

Mutations in the ATRX gene on the human X chromosome cause X-linked α-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.

Footnotes

↵ † To whom reprint requests should be addressed. E-mail: a.pask{at}zoology.unimelb.edu.au.
Data deposition: The sequences reported in this paper has been deposited in the GenBank database (accession no. AF303445).
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.230424497.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.230424497
Abbreviations:

ATRX,

α-thalassemia and mental retardation associated with the X chromosome;

ATRY,

α-thalassemia and mental retardation-like gene on the Y chromosome;

SRY,

sex-determining region on the Y chromosome;

SOX3,

SRY-like HMG box containing gene 3;

PAR,

pseudoautosomal region;

RT-PCR,

reverse transcription–PCR