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Exploring weird Australian genomes

By Jenny Graves - posted Tuesday, 6 June 2006


The platypus is even more distantly related to humans than kangaroos. There is a huge amount of interest in the platypus because it has characteristics that seem rather reptile and bird-like: for example they lay eggs. There is a lot of international interest in how the platypus evolved.

The platypus genome is surprisingly small - somewhere between that of a bird and a placental mammal. The platypus has 26 chromosomes, many of which are small and hard to work with. We are able to clone platypus genes and map them to chromosomes. But when we line the chromosomes up we find something very strange. Most of the chromosomes are perfectly normal - two copies in both males and females - but 10 chromosomes don’t have a partner in males.

These chromosomes that don’t have pairs all turn out to be sex chromosomes, 5X chromosomes and 5 Y chromosomes. At male meiosis they form a big, long, strange-looking chain with alternating Xs and Ys. We have no idea how they make baby platypuses or how baby platypuses know what sex they are supposed to be. But we have some evidence that all five X chromosomes go into one sperm and all five Y chromosomes go into another sperm and that’s how sex is determined.

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The chain is also interesting because we find that the X chromosome at one end of the chain is homologous to the mammalian X and Y chromosome, and the X chromosome at the other end is homologous to the bird sex chromosomes. Scientists thought that mammalian and bird sex chromosomes were completely different and evolved separately, but we now think this is wrong. Humans probably started off with the same system that birds and reptiles had and evolved a new system by exchanging our sex chromosomes with other chromosomes. This has been quite a surprise in the sex chromosome world.

There are two reasons why weird Australian mammals are especially important. One is that they’re very distantly related to humans, as I mentioned before, and this gives us a good opportunity to discover genes and the sequences that control them. The other is they’re different enough to have unique traits that might be useful.

If we look at a map showing how animals are related, we see how different Australian mammals are. There are three groups of mammals and Australia has a monopoly on two of them - marsupials and monotremes. The important thing is they shared a common ancestor so long ago that there are lots of differences in gene sequence and arrangement that we can use.

One surprising use for these different genomes is the discovery of new genes. Our laboratory has actually discovered 13 new human genes, mostly by accident, when we were looking for something else. It turns out that looking for a homologue in marsupials is actually a jolly good way of finding new genes.

We first hit the headlines when we were looking at a gene that was supposedly the male-determining gene. Students in my laborstory discovered that this gene was not on the Y chromosome in kangaroos and other marsupials, where it should have been if it’s the correct male determining gene. So it was the wrong gene. That led my student, Andrew Sinclair in London, to isolate the SRY gene on the human Y chromosome - which is also found on the kangaroo Y chromosome - and this is the right gene. That finding led to the isolation of a gene on the X chromosome called SOX3 - the female partner of SRY - and this also turns out to be a very important gene.

Similarly, we were looking for a gene on the human Y chromosome that is important in making sperm. We searched for and found a kangaroo version of it. But unexpectedly we found it had a homologue on the X chromosome and we were able to clone the human version, which we call RBMX. It maps to a very interesting region which is deleted in families with mental retardation. Since then we have cloned this gene in a zebra fish, knocked it down - that is we made it express less - and those zebra fish have a brain that rots away. So we seem to have accidentally discovered yet another gene that is probably required for building a brain and making it work.

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Kangaroos do reproduction very well and this is one unique trait we hope to exploit. The female can switch on and off embryonic development and they have a very sophisticated milk system that we can possibly learn from.

At a very early stage the kangaroo embryo can go into a quiescent state and stay there for up to 11 months before the signal is given to resume development. Of course, we would love to know what genes are involved in turning off and then turning on embryonic development because it would mean we could better understand development and possibly manipulate it in domestic animals and maybe even humans.

The kangaroo is born at a very immature stage - about the size of a jellybean and with no back legs or gonads. It crawls up into the pouch, latches onto a teat and develops under the influence of factors in the milk.

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This is an edited version of the Macfarlane Burnet Lecture 2006 given on May 3, 2006 as part of Science at the Shine Dome at the Australian Academy of Science.



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About the Author

Professor Jenny Graves is the Research Director at the Australian Research Council’s Centre for Kangaroo Genomics and Head of the Comparative Genomics Research Group at the Research School of Biological Science at the Australian National University (ANU).

Creative Commons LicenseThis work is licensed under a Creative Commons License.

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