Mystery of gene-packed X chromosome finally solved

© Regis Duvignau
Although the X chromosome contains about 2,000 genes, compared to 78 in the Y chromosome, for years it racked scientists’ brains as to why so few of those genes were actually necessary.

The answer may lie in a lack of pairing. In humans, males have XY chromosomes, while females have XX, but only one of them is active. So both males and females have just one active X chromosome.

The unusual genetic makeup of the X chromosome was discovered in 2002: it contains only a small amount of genes that are necessary for cell function, so-called ‘housekeeping’ genes. 

Researchers from the University of Bath teamed up with Uppsala University and the FANTOM consortium. They analyzed the largest data collection on gene expression in the world and examined the X chromosome’s activity compared to that of other chromosomes. 

Gene expression is the process by which the heritable information in a gene is made into a functional gene product.

It turned out that the X chromosome’s peak level of gene expression was under half of the levels shown in other chromosomes. The latter, however have two active copies as opposed to just one active copy of the X chromosome. 

The study, published in the PLos Biology journal, was led by Professor Laurence Hurst, director of the Milner Centre for Evolution based in the Department of Biology & Biochemistry at the University of Bath.

"In the end, we have found the answer to be quite simple. Whereas most chromosomes operate in pairs, meaning there are two copies of each gene in every cell, in contrast, we only have one active copy of the X chromosome,” Hurst said in the press release.

“This means it is not sustainable for highly active genes to be on the X chromosome. Housekeeping genes tend also to be highly active – they just couldn’t survive on the X,” he added.

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Hurst likened the chromosome situation to a busy road. 

“A consequence of having a single chromosome is that, like a one-lane road, there will be gene expression traffic tailbacks on the X chromosome especially at peak periods. Hence our X chromosome will not be a tolerable home for the most highly-expressed genes.”

These findings may be useful for research in new medical treatments such as gene therapy. For one, it suggests that replacement genes should not be inserted into the X chromosome because traffic tailbacks may limit the extent to which the gene can be expressed.