Back in 2002, scientists discovered that the X chromosome possessed an unusual genetic makeup, consisting of only a small amount of genes necessary for cell function. Although scientists have been baffled over this finding for years, researchers from the University of Bath and Uppsala University, in conjunction with the FANTOM consortium, have solved the puzzle. The team analyzed the largest compendium of data on gene activity in the world and examined the activity of the X chromosome in comparison to other chromosomes. The results showed that the X chromosome's peak level of gene expression was under half of the levels shown in other chromosomes with two active copies.

"Since we showed that X-linked genes tend to be relatively tissue specific over a decade ago, the reason as to why the X chromosome is so odd has bugged me," said Laurence Hurst, who participated in the research, in a press release. "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."

"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.

The team also managed to identify specific genes that have moved from the X chromosome to other chromosomes over the course of evolution and found that genes that make their way onto the X chromosome have lower peak rates of expression in comparison to genes that have migrated away from the X chromosome.

"It's a bit like traffic on a busy road - a highway with two lanes can have a lot more and faster traffic on it than a single lane highway," said Hurst. "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."

Furthermore, the team also found that even the most highly expressed genes on the X chromosome were less likely to increase their expression over the course of evolution.

"This fits with our traffic analogy as, if there is a tailback, it is hard to increase the speed of the cars on the road," said senior author Lukasz Huminiecki.

The results were published in the Dec. 18 issue of PLOS Biology.