XIST, not as important as previously thought

May 1, 2007 11:19 GMT  ·  By

Kangaroos hit again on one of the myths of the sex genetics.

When it was discovered in the early '90s, the XIST gene was regarded as essential in the process of inactivating the supplementary X chromosome in females. The gene has been believed to switch off the extra X chromosome during embryonic development and an entire field of research focused on this gene in an attempt of getting detailed information on how genes control the normal development, and how they lose it in various genetic disorders or cancer.

The switching off of one X chromosome is crucial in getting the right gene dosage in females (which have one more X chromosome than males do).

It is present in both placental mammals (most current mammals, which give birth to more or less developed offspring) and marsupials (pouched mammals, like kangaroos and possums), which split off from a common ancestor 180 million years ago.

The hit has come when Professor Jennifer Graves, the Head of the Comparative Genomics Group at the ANU Research School of Biological Sciences (RSBS) and director of the multi-university ARC Centre for Kangaroo Genomics, and RSBS PhD student Tim Hore, discovered that the marsupials lack the XIST gene, exactly like platypus (which split off from the rest of mammals even earlier).

Thus, XIST evolved later in the placental mammals, after they split off from marsupials and its importance in the development and X inactivation is not as important as previously thought. "We thought that if XIST really was so critical, we should have been able to find a copy of this gene in kangaroos. We've been looking since 1995, but found no trace of it. But this wasn't absolutely convincing because we could never be sure that it wasn't hiding out somewhere, or had changed so much in evolution we couldn't recognise it," said Graves.

The researchers analyzed isolated kangaroo and platypus genes located on the correspondent situs for XIST in placental genome. "To my surprise, these genes mapped far apart on the marsupial X. I sequenced the DNA containing these flanking genes and found neither contained anything like the gene XIST. XIST just does not exist in marsupials", said Hore. "The research indicates that XIST evolution may correlate to some of the molecular changes regarded as slight evolutionary improvements in stabilizing the X inactivation process," said Graves.

"Just like our work of two decades ago showing that the favored candidate for sex determination was the wrong gene, this finding challenges a favored hypothesis and shows us how complex control systems are built up out of simpler elements of evolution."