Scientists have found genetic evidence for what some men have long suspected: It is dangerous to make assumptions about women. The key is the X chromosome, the feminine sex chromosome that all men and women have in common. In a study published on Thursday in Nature, scientists have found an unexpectedly large genetic variation on the X chromosome among women. The findings were published in conjunction with the first comprehensive decoding of the chromosome, which appeared in the same journal. Females can differ from each other almost as much as they do from males in the behaviour of many genes at the heart of sexual identity, researchers said.‘‘Literally every one of the females we looked at had a different genetic story,’’ said Duke University genetics expert Huntington Willard, who co-wrote the study. ‘‘It is not just a little bit of variation.’’ The analysis also found that the obsessively debated differences between men and women are, at least on the genetic level, even greater than previously thought. As many as 300 of the genes on the X chromosome may be activated differently among women than among men, said molecular biologist Laura Carrel at Pennsylvania State University College of Medicine, the other author of the paper. All told, men and women may differ by as much as 2 percent of their entire genetic inheritance. That degree of difference is greater than the hereditary gap between humankind and its closest relative —— the chimpanzee. ‘‘In essence,’’ Willard said, ‘‘there is not one human genome, but two —— male and female.’’ Until now, researchers considered the genetic shuffle of sex chromosomes at conception a simple matter of genetic roulette. The chromosomes that dictate sexual development are mixed and matched in predictable combinations: A female inherits one X chromosome from each parent; a male inherits an X chromosome from his mother and a Y chromosome from his father. To avoid any toxic effect from double sets of X genes, female cells randomly choose one copy of the X chromosome and silence it —— or so it was believed.The new analysis found that the second X chromosome is not a silent partner. As many as 25 percent of its genes are active, serving as blueprints to make necessary proteins. To investigate this variation, Carrel and Willard isolated cells from 40 women and measured the activity of hundreds of genes to see whether those on the second X chromosome were active or silenced. Although those extra genes were believed to be turned off, they found that about 15 percent of them were still active in all female cells. In some women, up to an additional 10 percent of those X-linked genes showed varying patterns of activity. ‘‘This is 200 to 300 genes that are expressed up to twice as much as in a male or some other females,’’ Willard said. ‘‘This is a huge number.’’ The genetic variation among women might help account for differing gender reactions to prescription drugs and the heightened vulnerability of women to some diseases, several experts said. ‘‘The important question becomes how men and women actually vary and how much variability there is in females,’’ Carrel said. ‘‘We now might have new candidate genes that could explain differences between men and women.’’Researchers were surprised that they found so many unexpected differences in the behavior of the one sex chromosome that men and women share. While there is dramatic variation in the expression of genes on the X chromosomes that women inherit, there is none among those in men, the researchers reported.
