MRC National Institute for Medical Research, London
Science for Health
Opossums and X-inactivation
27 August 2009
Male and female mammals differ in several fundamental respects, but one of the most striking is their sex chromosome make-up: males have one X chromosome while females have two. This causes a potential problem because females have twice the dose of X chromosomal genes that males have. In order to overcome this imbalance in X chromosome dosage, females inactivate the genes on one of their two X chromosomes. In mice, X-inactivation occurs in the early female embryo and is mediated by a gene called Xist. However marsupials, another mammal that diverged from mice some 145 million years ago during evolution, have no Xist gene although female marsupials are still able to undergo X-inactivation. How they do this remains the subject of debate.
For a long time it has been believed that X-inactivation in marsupials occurs by a fundamentally different mechanism, in which the X chromosome is silenced in the father’s germ line during development of the sperm and is then passed to the daughter at fertilisation in an already inactive state. This model, called the ‘pre-inactivated X chromosome’ hypothesis, has also been proposed to be the evolutionarily ancient form of X-inactivation in mammals.
In order to test this hypothesis, James Turner (pictured) and his group in NIMR's Division of Stem Cell Biology and Developmental Genetics have systematically studied the activity of many genes along the marsupial X chromosome during male germ line development and have compared it with that seen in female tissues. Contrary to the ‘pre-inactivated X chromosome’, they have found that all of the X-linked genes studied are active during sperm development in the male and that these genes are subsequently inactivated in the female.
Our findings are surprising because they suggest that the timing of initiation of X-inactivation in marsupials is very similar to that of mice. This overturns a model that has been around since the 1970s. The next important question will be how female marsupials inactivate one of their X chromosomes when they have no Xist gene.
James Turner
Original Article
The research findings are published in full in:
Shantha K. Mahadevaiah, Helene Royo, John L. VandeBerg, John R. McCarrey, Sarah Mackay, and James M.A. Turner (2009) Key features of the X inactivation process are conserved between marsupials and eutherians Current Biology, epub ahead of print. Publisher abstract
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