War of the sexes: How chromosome study shows male and female genetic differences

Genetic differences between men and women are more extensive and profound than previously believed, according to a study that unravels the chemistry of the sexes.

Analysis of the "X" chromosome - the female sex chromosome - has revealed that women are genetically more complicated than men. The findings reveal that men have taken a genetic battering that has dwindled the size of their own "Y" chromosome.

The battle of the sexes has its roots in a 300-million-year struggle between the X and the Y chromosomes which have vied with each other for influence over successive generations of males and females. Scientists showed yesterday that the X chromosome has retained its physical integrity while the Y of men has dwindled in size and power to become a shadow of its former self.

The first comprehensive survey of the genes that are active on the X chromosome has revealed the dominant position that it has gained in the long war of attrition with its male counterpart. One consequence is that boys are more prone to genetic diseases than girls.

While the Y chromosome has retained fewer than 100 working genes, the X has more than 1,000 and is able to deploy them more intricately. This has resulted in the female genome becoming very different to that of men, the scientists said. While women have two X chromosomes, men only have one, inherited from their mothers. The second sex chromosome of men is the Y of their fathers, thought to have evolved from a degenerate version of an ancient X chromosome as long as 300 million years ago.

Huntington Willard of Duke University in Durham, North Carolina, and one of the leaders of the study published in the journal Nature, said the findings show that, when the X chromosome occurs in women, it behaves so differently to when it resides in men that it has in effect resulted in the evolution of another human genome.

"We now know that 25 per cent of the X chromosome - some 200 to 300 genes - can be uniquely expressed in one sex relative to the other. In essence, therefore, there is not one human genome, but two - male and female," Professor Willard said.

Originally it was thought that one of the two X chromosomes in women was completely turned off or inactivated so that the female body did not become inundated with twice as many X-chromosome genes as men. The latest study paints a more complex and subtle picture.

Laura Carrel of Penn State College of Medicine looked at inactivity levels in the X chromosomes of 40 women. She found that 65 per cent of X-chromosome genes were totally inactivated, 20 per cent were inactivated in some samples but not others, and 15 per cent escaped inactivation altogether.

"Our study shows that the inactive X in women is not as silent as we thought. The effects of these genes from the inactive X chromosome could explain some of the differences between men and women that aren't attributable to sex hormones," Dr Carrel said. In other words, the physical and emotional differences between men and women may run deeper than those which are caused simply by hormones. The study showed, for instance, that the 15 per cent of genes that are active on the "inactive" X chromosome are present at higher levels in women than they are in men.

"These differences should be recognised as potential factors for explaining normal differences between the sexes but also gender differences in how certain diseases are manifested, progress and respond to treatment," Dr Carrel said.

Girls have two X chromosomes so defects in one can be corrected by the other. But, as boys have only one X chromosome, they suffer from inherited disorders when the X is damaged, such as haemophilia, colour blindness and Duchenne muscular dystrophy.

Mark Ross, project leader of an X-chromosome study at the Wellcome Trust, said that more than 300 diseases had been mapped to defects on the chromosome and 40 genes had been specifically isolated that are involved in conditions such as cleft palate and blindness.

"From studying such genes, we can get remarkable insight into disease processes ... but the importance of the sequence goes beyond the biology of individual genes," he said. "We can see the way evolution has shaped the chromosomes that determine our gender to give them their properties," he said.

Comparing the genetic sequences of the X and Y chromosomes showed extensive degeneration of the Y which has retained only a handful of shared genes, Dr Ross said.

David Bentley, the head of human genetics at the Sanger Institute in Cambridge, said the X chromosome has been pivotal in discovering and studying defective genes that cause inherited diseases. "There are many more genetic disorders of the X chromosome where the underlying gene is still to be found. Now we can make use of the finished sequence to find them," he said.