UNEXPECTED and baffling variations between individual women have emerged from a study of the X chromosome.
While men have one X and one Y chromosome, women have two X chromosomes. If all the genes on both X chromosomes were active, women would get an overdose of the proteins these genes code for. To prevent this, every cell in the early female mammalian embryo switches off one of its X chromosomes, which then remains silent in all the descendants of that cell 鈥� a process called X inactivation.
However, while some cells switch off the X inherited from the father, others switch off the X chromosome from the mother. So most women are a mixture of two different cell populations, each of which is expressing genes on a different X chromosome (快猫短视频, 10 May 2003, p 42. Occasionally this can have consequences. For instance, if one X chromosome carries a gene variant causing a skin disease or pigmentation defect, women are actually visibly 鈥減atchy鈥�.
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The excess X genes in women may have other implications. Conflict between the two cell populations in women鈥檚 bodies has been suggested as a reason why women are more prone to autoimmune diseases than men. This 鈥渋nternal war鈥� idea has even been claimed to cause the higher incidence of identical girl twins; the dissimilar cell populations in a female embryo might repel each other to the point where they split.
Now Laura Carrel of Pennsylvania State University College of Medicine in Hershey and Huntington Willard of Duke University in Durham, North Carolina, have shown that X inactivation is remarkably variable. In skin cells from 40 women, they looked at a selection of X genes to see if any on the silenced chromosome were active. Small sequence variations allowed them to tell whether an expressed gene was on the active or inactive chromosome.
The findings are striking. First of all, not all of the genes on the supposedly inactivated X were switched off 鈥� perhaps as few as 65 per cent. That throws up a mystery: if inactivation is crucial to prevent an overdose of X genes, how can so many remain active in women? Could the double dose of non-silenced genes be responsible for some of the differences between men and women?
Even more unexpectedly, another 20 per cent or so of the genes studied were inactivated in some women but not others. 鈥淓very one of them had a unique pattern of gene expression,鈥� Willard says. 鈥淎ll of that variation is completely unique to women.鈥�
The results imply that some women are getting a double dose of these genes, while others are not. Why X inactivation should vary so much between individuals is even harder to explain than variation in gene expression between different parts of the X itself. 鈥淲e now know that 25 per cent of the X chromosome 鈥� 200 to 300 genes 鈥� can be uniquely expressed in one sex,鈥� Willard says. 鈥淚n essence, therefore, there is not one human genome, but two 鈥� male and female.鈥�
And things could get more complicated still. It is possible that as well as variations in the extent of X inactivation between individual women, there could be variation in different tissues in every woman鈥檚 body, meaning women could be hybrids containing several different cell types, not just two.
