Published today in Science, the study by researchers from Monash University, several institutions in Japan and the University of Queensland sheds light on the molecular basis of XY sex reversal, which occurs in approximately 1 in 50,000 live births.
Individuals with XY sex reversal appear female, but have male sex chromosomes.
The study represents the first time that an epigenetic regulator of sex determination has been established. Epigenetic regulation refers to any element that is independent of the DNA sequence but which affects gene expression – in this case, an enzyme.
Researchers from Kyoto University made the discovery by accident when they found that 80 per cent of offspring from mice that had been specially bred without an enzyme – H3K9 demethylase Jmjd1a – were female.
The researchers referred the findings to experts in the genetic basis of sex determination, including Associate Professor Dagmar Wilhelm of Monash University’s Department of Anatomy and Developmental Biology.
“It is highly likely that these results will be replicated in humans and will be helpful in explaining the occurrence of some disorders of sex development – which are more common than most people realise,” Associate Professor Wilhelm said.
The researchers found a direct link between Jmjd1a and SRY, a gene on the Y chromosome that triggers male development.
DNA is wrapped around proteins called histones, much like wool around a spool. In this form, it is tightly packed and genes cannot be expressed. Jmjd1a causes the DNA in the area directly around SRY to unpack and allows SRY to become active, triggering male sexual development.
“SRY is the male determining factor. This one gene is necessary and sufficient to drive male development,” Associate Professor Wilhelm said.
“If Jmjd1a is absent, SRY cannot be expressed, the male development process cannot begin and XY individuals tend to develop as females.”