Bird sex gene identified

By Hilary Miller 11/09/2009 In mammals, sex is determined by genes contained on sex chromosomes — males have an X and a Y chromosome, and females have two X chromosomes.  In birds things are quite different, as it is the male that has two of the same type of sex chromosome.  Male birds have two Z chromosomes and female birds have a Z and a W chromosome.  In mammals, the Y chromosome contains a gene called SRY, which ’switches on’ the male sex determining pathway.  So if you have the SRY gene you develop testes, and if you don’t you develop ovaries.

Until now, the identity of the master sex-determining gene in birds has been a mystery.  The Z and W chromosomes of birds are not related to the X and Y chromosomes of mammals, and birds do not have an SRY gene.  Research published in Nature yesterday appears to have solved this mystery, with evidence that the DMRT1 gene, located on the Z chromosome, is the bird sex determining gene.

baby chickensDMRT1 has long been suggested as a good candidate for the ’master switch’ gene in birds, but until now this has been difficult to prove due to the technical difficulty in knocking out expression of genes in large, yolky bird eggs.  Craig Smith, Andrew Sinclair and colleagues from the University of Melbourne have now succeeded in silencing expression of DMRT1 in chicken embryos using a method called RNA interference.  They found that in genetically male chicken embryos where levels of the DMRT1 protein were reduced by RNAi, the gonads developed into ovaries rather than testes, suggesting that DMRT1 is required for testes development.  These embryos also showed reduced expression of a male marker gene SOX9, but levels of a female marker gene aromatase (which is not present in normal male embryos) increased.  Reducing DMRT1 expression had no effect on genetically female embryos – their gonads developed into ovaries as usual.

These results suggest that DMRT1 alone can determine whether an embryo becomes male or female.  However, unlike in mammals, where sex is determined by presence or absence of SRY, DMRT1 appears to act in a dosage-dependent manner.  Male birds have two copies of the gene (one on each Z chromosome) so produce twice as much DMRT1 protein as female birds.  The results of Smith and colleagues suggest that DMRT1 levels need to reach a certain threshold before the male developmental pathway is switched on, and this level can only be reached by birds with two Z chromosomes.

Unfortunately, Smith and Colleagues were unable to conduct the converse experiment to test whether you can turn genetically female embryos into males by overexpressing DMRT1.  This is because their experiments resulted in overexpression of DMRT1 in all tissues, not just the gonad, which is lethal to the developing embryo.  Future refinements of their method should enable them to direct expression to the gonad only, mimicking what would happen in a genetically male embryo and confirming the role of DMRT1 as the master sex switch.

This study fills a large hole in our understanding of sex determination in vertebrates.  DMRT1 appears to be involved in sex determination across a variety of vertebrates, suggesting it has an ancient role.   This is backed up by the fact that early mammalian lineages and some reptiles have sex chromosomes related to the ZW system of birds, not the XY system of later mammals, suggesting that SRY is only a recent arrival on the sex determination scene.

Smith, C., Roeszler, K., Ohnesorg, T., Cummins, D., Farlie, P., Doran, T., & Sinclair, A. (2009). The avian Z-linked gene DMRT1 is required for male sex determination in the chicken Nature, 461 (7261), 267-271 DOI: 10.1038/nature08298