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

Nat Commun. 2014 Jun 20;5:4157. doi: 10.1038/ncomms5157.


Sex chromosomes harbour a primary sex-determining signal that triggers sexual development of the organism. However, diverse sex chromosome systems have been evolved in vertebrates. Here we use positional cloning to identify the sex-determining locus of a medaka-related fish, Oryzias dancena, and find that the locus on the Y chromosome contains a cis-regulatory element that upregulates neighbouring Sox3 expression in developing gonad. Sex-reversed phenotypes in Sox3(Y) transgenic fish, and Sox3(Y) loss-of-function mutants all point to its critical role in sex determination. Furthermore, we demonstrate that Sox3 initiates testicular differentiation by upregulating expression of downstream Gsdf, which is highly conserved in fish sex differentiation pathways. Our results not only provide strong evidence for the independent recruitment of Sox3 to male determination in distantly related vertebrates, but also provide direct evidence that a novel sex determination pathway has evolved through co-option of a transcriptional regulator potentially interacted with a conserved downstream component.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Biological Evolution*
  • Cell Differentiation / physiology
  • Chromosome Walking
  • Chromosomes, Artificial, Bacterial
  • Cloning, Molecular
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology*
  • Immunohistochemistry
  • In Situ Hybridization
  • India
  • Male
  • Molecular Sequence Data
  • Mutation / genetics
  • Oryzias / genetics*
  • Oryzias / physiology
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / physiology*
  • Sequence Analysis, DNA
  • Sex Determination Processes / genetics*
  • Sex Determination Processes / physiology
  • Testis / cytology
  • Testis / growth & development
  • Transforming Growth Factor beta / metabolism
  • Y Chromosome / genetics*


  • SOXB1 Transcription Factors
  • Transforming Growth Factor beta

Associated data

  • GENBANK/AB775142
  • GENBANK/AB775143
  • GENBANK/AB909496
  • GENBANK/AB909497