Luck of the draw for XISTence

A UK physicist has uncovered how female cells are able to choose randomly between their two X chromosomes and why that choice is always lucky.

At an early stage in the development of a woman's fertilised egg the cells need to silence one of her two X chromosomes.

Both X chromosomes in a cell have a gene called XIST that, if activated, seals the chromosome behind a barrier of RNA, preventing the activation of any other gene.

Researchers believe that this gene can be itself blocked by a plug of proteins forming on top of its specific location on the chromosome but they had little idea as to why this should happen randomly to one X chromosome's gene and not the other.

Now researchers led by University of Warwick physicist Dr Mario Nicodemi have explained how this randomness occurs and why it is beneficial.

Coming at the problem from the perspective of a physicist, Nicodemi has found an explanation for the random selection based on thermodynamics. Research has already shown that at the key moment in this process both X chromosomes are brought close together within the cell.

The Warwick researcher paper says that what happens next is that material for a protein plug then begins to gather around both of the XIST suicide genes on each X chromosome.

This starts a race between the two build ups of protein. Inevitably one of these two nascent protein plugs narrowly wins that race and reaches an energy state in which it can pull together all the material building up in both plugs into a single protein plug.

That single plug then closes off one of the XIST suicide genes, allowing its host X chromosome to continue to operate. However the other XIST suicide gene is now freed to activate and shuts down its X chromosome.

Since putting forward this explanation, US researchers have observed actual plugs of protein shutting down X chromosome XIST genes in a manner giving further confirmation to Nicodemi's research.

Nicodemi believes the randomness actually does give an evolutionary advantage. The mechanism means equal numbers of both the maternal and paternal X chromosome are preserved in the gene pool and the resultant population thus has more chance of surviving any biological threat targeted at a single version of the X chromosome.

"Symmetry breaking Model in X Chromosome Inactivation" in Physical Review Letters, vol.98 page 10810

Source: University of Warwick