The DNA Switch that Separates Men from Women

(Credit: Science Photo Library/NTB Scanpix)

Technically, without intervention, all embryos would develop into females. Some of the genes that are involved in altering embryonic development to form testes, a penis, and other male traits, have been identified. But now, a 557 base DNA switch that turns female embryos into males has been located on the Y chromosome.

The switch is located half a million bases away from the sox9 gene, which is known to kick-start the development of the testes. However, looping of the chromosome means that the switch is brought into contact with sox9 to activate it.

First Linear Map of Y Chromosome Centromere Published

These types of DNA stretches, that control the activation of distally located genes, are known as enhancers. Across the genome about 1 million enhancers control nearly 21,000 genes. It has been long known by developmental biologists that one or more enhancers help to activate Sox9 early in the developmental process, but they were at a loss to figure out exactly which ones were most important.

Robin Lovell-Badge, a developmental biologist at The Francis Crick Institute in London worked with Danielle Maatouk and her team at Northwestern University in Chicago, Illinois, to use multiple techniques to find the most important enhancers that interact with sox9, reports Science. They even included new methods that seek out places where enhancer-activating proteins interact with DNA or the places where DNA has unfolded a little to make way for these proteins.

As of yet, the study has only been carried out in mice but Lovell-badge says that “It’s so important in mice, it’s probably important in humans as well. It may be that you could use this [finding] to understand, and perhaps actually change, the gonad function.”

About one in every 5500 human babies born has some problem related to its gender. Some have the male chromosome but no testes, for example, and doctors can figure out the reason for these abnormalities in fewer than half of all cases. Now, they can check to see whether the human version of this enhancer is disrupted in some way, Capel says. Harley, for example, has already started looking at the genomes of his patients to see whether their unexplained sex determination problems can be traced to this switch.

Capel predicts an even broader impact of the enhancer-finding methods. The approach taken “may be a way of defining what might be causal for diseases.”