Women get extra dose of X-chromosome genes

Data may help to explain differences between women and men.

Women?s second X chromosome may be doing more than we thought. Credit: © SPL

Although men and women may often act like separate species, scientists have long believed they are really not that different when it comes down to their DNA. But now, researchers have found that the sexes differ more than we thought, particularly when it comes to the genes on one crucial chromosome.

Every woman carries a double dose of the X chromosome, whereas men carry one X and a Y. Women don't express both copies of the X chromosome in their cells: in each cell they shut one copy down (the 'inactive' X) and use the other.

However, it seems that the inactive X doesn't just sit down and shut up. The first of two research papers on the human X chromosome, both published in Nature, analyses the complete sequence of the chromosome1. The second shows that women still express many genes from their inactive X chromosomes2. What's more, different women express different genes from the inactive X.

“It doesn't provide evidence that genes explain the differences between men and women, but it does provide candidates. Laura Carrel , Pennsylvania State College of Medicine, Hershey”

Taken together, the two papers may eventually explain some of the behavioural and biological differences between individual women, and perhaps, between women and men.

Quietly active

Scientists already had an idea that the inactive X chromosome is not completely silenced. But they did not realize just how active it actually is.

Hunt Willard of Duke University in Durham, North Carolina, and Laura Carrel of the Pennsylvania State College of Medicine in Hershey, investigated this by designing tags that bind to messages from X-chromosome genes. The tags allowed scientists to pinpoint which genes were escaping inactivation.

Using these tags to probe samples from 40 women, Willard and Carrel found that 15% of the genes on the inactive X chromosome were active in every sample. Another 10% of genes from the inactive X were switched on in just some of the samples.

"The data are so striking," says Willard. "Every female is expressing a different subset of X-linked genes at different levels."

Because the genes expressed from the inactive X are also expressed from a woman's active X, women get a higher dose of these genes than men. So these genes may underlie traits that differ between the sexes. The scientists caution, however, that they have only investigated one type of cell, and that to draw any general conclusions the findings must be repeated in other kinds of cells.

"It doesn't provide evidence that genes explain the differences between men and women, but it does provide candidates for such genes," Carrel says.

Cancer therapy

The X-chromosome sequence, which is now 99.3% complete, has also revealed a few surprises of its own. The international team that assembled the sequence found that about 10% of X genes belong to a family (the 'testis-antigen genes') that has been linked to cancer.

These genes are promising targets for potential therapies, because they are only expressed in cancer and in the male reproductive organs. Therapies that knock out tissues expressing the testis-antigen genes should leave patients' other organs intact.

Other key findings from the X sequence could help us understand how the chromosome evolved, and how it sends the signals that shut down the inactive chromosome. Investigating these leads will keep scientists busy for a long time to come, says genomicist Jenny Graves of the Australian National University in Canberra.

"Having the quantitative picture of the X is absolutely new, and I think this gives us a really good picture of the whole X chromosome," Graves says.

References

  1. 1

    RossM. T. et al. Nature, 434. 325 - 337 (2005).

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  2. 2

    CarrelL. & WillardH. F. et al. Nature, 434. 400 - 404 (2005).

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Pennsylvania State College of Medicine, Hershey

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X chromosome in focus

X chromosome web focus

Y chromosome web focus

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Human X chromosome project overview

US National Library of Medicine: information on chromosome X

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Check, E. Women get extra dose of X-chromosome genes. Nature (2005). https://doi.org/10.1038/news050314-7

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