Friday, March 9, 2012

Female genes make males more masculine

Differences between males and females are not always straightforward. In some situations, female hormones are used by men, while male hormones can do their job in a female body. In our DNA, there are various blueprints for male and female hormones. Now, scientists from the University of Virginia have shown that sex-specific genes have unexpected effects. It appears that a certain female genetic setup actually makes males more masculine. It is an interesting find, considering the fact that scientists have long thought that hormones, and not the genetic setup, are the deciding factors between male and female behaviour.

Our DNA is packed in individual structures called chromosomes. Each animal species has a different set, but humans possess 23 pairs: for each chromosome there is an almost identical copy that is normally shut down. The chromosomal setup also decides whether an organism develops to be a male or female. For this, animals possess a pair of sex chromosomes: two X chromosomes make a female, while an X and Y chromosome pair result in a male. There is a gene on the Y chromosome that overturns the 'default' development program resulting in a female organism. It is known as the SRY gene and it is the determining factor to switch from female to male development.

At the University of Virginia, scientists were experimenting with the genetic setup in mice. Using genetic engineering, they removed the SRY gene from the Y chromosome, and put it on an X chromosome. Then, they allowed an embryo with XX sex chromosomes, with the addition of the SRY gene, to develop into a mature mouse. Because of the SRY gene, the animal developed into a male, but it has more female genes due to the presence of two X chromosomes. To their surprise, these modified male mice behaved in a more masculine way. They assessed sexual behaviour as a model for masculinity, and found that the XX males showed increased tendency to mount females and they found an increase in ejaculation.

In their experiments, the XX mice were compared with ordinary XY males. Even mice with a genetically modified XXY setup behaved more masculine compared to their XY wildtype counterparts. Apparently, there is something on the X chromosome that makes males behave more masculine, despite being a female-branded chromosome. It is likely that there are genes on the X chromosome that influence masculine behaviour, which is surprising because you would expect it to be present on the Y chromosome instead. Sadly, it is impossible to test mice with an YY setup, because such genetic constructions are not viable for life. 

In addition to showing that the X chromosome is capable of increasing masculinity, the scientists illustrated a second point of interest. Because the second X chromosome appears to influence behaviour, it must be actively expressing its genes. Scientists have long thought that the second X is shut down in females: they use one of the chromosomes, and inactivate the other one, because there is no use for two of them. The same applies for somatic, which is jargon for non-sexual, chromosomal pairs. Recent studies have hinted otherwise, and this study further illustrates that the second X chromosome is indeed active. It is estimated that about 25 percent of the genes on the second X are active. 

The question remains whether it works the same for humans, although it is likely. There are not much differences between development of the body plan between mouse and human, though the eventual outcome of the mostly similar blueprints makes it look like they are very different. Our newfound knowledge may explain problems in sexual development. In some cases, it is impossible to assess whether a person is of the male or female sex, due to a lack of sexual organs, or because both versions are present. Additionally, sometimes a woman can be 'trapped' in a male's body, and vice versa. We may be able to gain a deeper understanding of these mechanisms by further exploring the data presented by this study.
Left: Y chromosome. Right: X chromosome.  The Y chromosome is smaller because it does little else than provide the SRY gene for male development.

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