Paul Thomas of the University of Adelaide, in collaboration with Robin Lovell-Badge from the Medical Research Council National Institute for Medical Research in London plus many other scientists from the U.S. and Australia, have found the genetic precursor to the gene that causes boys to be boys. When this gene, (SOX3) is overexpressed, XX mice embryos develop into males.
It has long been known that in mammals the gene SRY, found on the Y chromosome, is responsible for maleness. It had been thought that this gene might have evolved from an earlier gene called SOX3, which has been implicated in brain development. However, mutations that block the functioning of SOX3 have not been shown to effect sexual development. Rather than stunting SOX3, the researchers on this project ‘upregulated’ that gene, causing it to overproduce the Sox3 protein. When this was done, the resulting XX embryos turned out to be completely male in physiology and behavior (though they were sterile, being incapable of producing sperm).
Sex reversal (XY females or XX males) also occurs spontaneously in humans at the rate of about one in every 20,000 births. Upon genetic testing, the team found a couple of XX men who had variations in their SOX3 genes, but not in SRY.
Because SOX3 and SRY can activate the same maleness pathway, the researchers believe that SOX3, which also functions in neurological development, predated SRY. As Lovell-Badge explains:
It is now very likely that something similar to what has happened in the XX male mice and humans we describe also occurred in our early mammalian ancestors, and this led to the evolution not only of SRY, but of the X and Y chromosomes.