Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Review Article Sex Dev 2007;1:2–11 DOI: 10.1159/000096234 The Evolution of Sex Chromosomes and Sex Determination in Vertebrates and the Key Role of DMRT1 M. Ferguson-Smith Cambridge Resource Centre for Comparative Genomics, Centre for Veterinary Science, University of Cambridge, Cambridge, UK is singled out in this review because of its likely key role in sex determination both in birds and in reptiles with TSD. DMRT1 is one of the few sex genes that have been mapped in representative species of fish, turtles, crocodiles, amphib- ians, birds and mammals. Greater effort in comparative map- ping, sequencing and expression studies is required to dis- cover the other primary switch genes in vertebrates and to answer questions about their evolution. Copyright © 2007 S. Karger AG, Basel Our present knowledge of mammalian sex determina- tion is based on studies over 45 years ago, of Klinefelter and Turner syndromes in humans and mice that revealed the dominant Y chromosome factor in male differentia- tion. Studies in XX males led to the discovery of SRY as the primary testis determining factor (TDF) and many of the other known factors in the sex determination cascade (table 1) have been characterised by the careful investiga- tion of sex-reversed XY females. The work was initiated largely by pathologists and clinicians who studied pa- tients referred to them with disorders of infertility or sex differentiation. The solution of these problems has re- quired the collaboration and expertise of geneticists and molecular biologists. Disorders of sex determination are not lethal and so provide an excellent model for the study of biological systems. Key Words DMRT1  Sex determination  Sex differentiation  SRY  Vertebrates Abstract Mechanisms of vertebrate sex determination are reviewed in the light of what is known about the origin and evolution of sex chromosomes. All vertebrate males have testes that are similar in anatomy and in spermatogenesis. Despite a variety of sex chromosome systems, the same cascade of genes op- erate in the differentiation of testes and male genitalia. Only the primary signal or switch that initiates the cascade may be different. Genetic sex determination (GSD) occurs in most species, although temperature-dependent sex determina- tion (TSD) is the switch in some reptiles without GSD. SRY is the genetic switch in eutherians (placental mammals) and DMRT1 may have that function in birds and at least one spe- cies of fish. The switch in all other groups of vertebrates with either male or female heterogamety is unknown. DMRT1 is an ancient sex determining gene, found first in invertebrates, and is one of several genes expressed in higher levels in the vertebrate embryonic testis than in the embryonic ovary. It Received: June 19, 2006 Accepted after revision: August 10, 2006 Malcolm Ferguson-Smith Cambridge Resource Centre for Comparative Genomics Centre for Veterinary Science, University of Cambridge Madingley Road, Cambridge CB3 0ES (UK) Tel./Fax +44 1223 766 496, E-Mail maf12@cam.ac.uk © 2007 S. Karger AG, Basel 1661–5425/07/0011–0002$23.50/0 Accessible online at: www.karger.com/sxd Studies on comparative genomics and evolution were supported by a grant to M.F.S. from the Wellcome Trust.