Studying mice, researchers have found the first evidence in mammals of a battle between the X and Y chromosomes, which changes the balance of male and female offspring.
While most chromosomes and their associated genes are common to males and females, the sex chromosomes X and Y are an exception. Females have two X chromosomes while males have one X and one Y. The mother always passes down one of her X chromosomes to the next generation in the egg, so offspring sex is determined by whether the father passes on his X or Y chromosome in the sperm. This research showed that certain genes present on the sex chromosomes are able to selectively affect the fertilising ability of X- or Y-bearing sperm, thus skewing the balance of male and female offspring.
The concept is known as an intragenomic conflict and can result in a phenomenon called transmission distortion. It happens when a particular copy of a gene favours its own transmission to the next generation over others - essentially acting 'selfishly' and being transmitted to more than half of offspring.
Normally, both copies of a gene have an equal chance of being inherited. When transmission distortion affects genes on the X or Y chromosomes, this results in more female or male offspring.
The study was carried out by Julie Cocquet and Paul Burgoyne of the MRC's National Institute for Medical Research (now part of the Francis Crick Institute) along with Peter Ellis at the Cambridge University Department of Pathology. Dr Cocquet is now based in Paris at the Cochin Institute where she did the latter parts of the work.
To demonstrate the existence of an intragenomic conflict, Dr Cocquet and Dr Ellis studied genes called Slx/Slxl1 and Sly, which are related to each other. There are around 50 to 100 copies of Slx/Slxl1 on the mouse X chromosome and a similar number of copies of Sly on the Y chromosome. The proteins coded for by these genes change the expression of many other genes on the sex chromosomes (X and Y) in developing sperm. Slx turns on these genes, which skews the offspring sex ratio in favour of females. Sly has the opposite effect, switching off the same set of genes and skewing the ratio in favour of males. Collectively, Slx and Sly act as a 'thermostat', regulating sex chromosome expression and altering sex ratio one way or the other.
The scientists found that deficiency of either gene leads to severe fertility problems as well as a sex ratio skew, but that fertility is improved (and a normal sex ratio is restored) when both genes are deficient. They suggest that the conflict between Slx/Slxl1 and Sly is probably to blame for the amplification - or increase in number of copies - of genes on the mouse X and Y chromosomes, and may even have played a role in the evolution of separate subspecies of mice.
Dr Burgoyne explained: "Male mice that have lost part of their Y chromosome - and thus some copies of the Sly gene - produce more than 50 percent female offspring and show over-activation of multiple genes on their X chromosome. This provides strong evidence for transmission distortion."
He added: "To the best of our knowledge, this work is the first demonstration of a competition occurring between X and Y related genes in mammals. It also provides a biological basis for the idea that intragenomic conflict is an important evolutionary force, which impacts on individual genes, whole chromosomes and even the evolution of new species."
The paper, A genetic basis for a postmeiotic X versus Y chromosome intragenomic conflict in the mouse, was published inPLOS Genetics.
