Studying the genetic makeup of Australian
animals, like the platypus, sheds new light on the
evolution of our own species.
Image: Ian Elton

Professor Jenny Graves has long believed the genomes of Australia’s native animals hold a wealth of scientific treasure worth of thorough investigation. And now, with the sequencing of the platypus genome, that view has been vindicated.

The release of the fully sequenced platypus genome was announced in the journal Nature earlier this year and marks an important leap forward in our understanding of the genetic evolution of vertebrate life.

Graves was first Australian author on that paper. She’s also the leader of the Comparative Genomics Laboratory in the Research School of Biological Sciences at ANU. She believes the platypus genome serves as an important key to understanding our own biology. And, of course, it also allows us to better understand the biology of the platypus.

Genomics is the study of an organism’s entire genome, which is sum total of all its genes. The human genome, for example, contains around 20,000 genes. It is the combination of the genes we have and how they are controlled that helps shape who we are. The first genome sequence was of a bacterium, and was completed in 1995. The human genome sequence was completed in 2003. In all, around 25 species of mammals have now been sequenced including the cat, dog, horse, cow, human and African elephant. While costs are coming down, deciphering genomes is an expensive business. Each species costs many tens of millions of dollars.

So, why the international focus on the platypus? It’s an egg-laying monotreme, part of an ancient group of mammals with few living representatives (in Australia the monotremes are represented by the platypus and few species of echidna). Given the high cost, shouldn’t scientists have targeted something a little more mainstream, not a mammal oddity?

“The platypus is a very ancient offshoot of the mammal tree,” Graves says. “It was 166 million years ago that we last shared a common ancestor with platypuses and the platypus genome shows ancient links with birds and reptiles, thereby providing vital clues on our own genetic origins.”

Human genomics tells us the sequences that make up our genetic information but we still need to work out what the genes are and how they operate. Comparative genomics (comparing DNA sequences of different species) is a powerful tool in this process.

“We can line up the genomes of different species and spot what’s the same and what’s different,” Graves explains. “And what’s the same gives us very good clues as to what’s important, because things that are very important don’t change very much in evolution.

“We can actually use this line up to spot genes that we didn’t even know were there. And, most importantly, we can spot some of the little DNA sequences that turn these genes on and off. And that is critical to understanding a genome.

“As the science of genomics has developed it’s become clear that most mammals have roughly the same set of genes. But, of course, we don’t look much like a platypus. Why is that? The secret is how and when those genes are turned on and off. These little control switches are what makes us human, and a platypus a platypus.

“So, you hold the human genome up against the platypus genome, and up against other species, and when you see sequences that have been the same for 200 million years you know there’s something important there.

“The gene sequences themselves we now know quite a bit about; we know what to expect, we know how they make protein, and we can make a pretty good guess at what that protein does by relating it to other proteins that are similar.

“However, we know very little about what the rest of the genome does, and that’s the bit that contains the important little control signals that are very hard to spot because we don’t know what we’re looking for. It’s like looking for needles in a haystack but we don’t know what the needles look like. Comparative genomics is a powerful method for pin pointing these control signals and spotting the bits that have been conserved.”

Graves has long championed the importance of understanding the genomes of Australia’s unique mammal fauna. In addition to leading the white paper proposals that kicked the platypus genome work off, she also led the push to sequence the first marsupial genome, and is the Director of The ARC Centre of Excellence for Kangaroo Genomics (KanGO) that aims to map the kangaroo genome. While the importance of this work is now increasingly understood and appreciated, there was a time when the Australian fauna was regarded more with humour than serious scientific interest.

 “In the early days of my career I remember people laughing when I discussed kangaroos at overseas conferences. And if I said ‘wallaroo’ or ‘wombat’ they almost fell off their chairs. That’s because these creatures were regarded as animal oddities. They were weird mammals and I became the ‘weird mammal lady’.

“At least they’re listening, I thought to myself at the time. But, as it’s turned out, nobody’s laughing any more because we now know genomes from Australian animals are very important. They tell us a lot about ourselves because they are so distantly related from people and mice. Using the genomes from platypuses and kangaroos you can actually go way back in evolution and find out how things started and how things work and what’s been retained and what’s been changed.”

Back in those early days Graves was warned off wasting any time on marsupial genomes as many scientists suspected they probably didn’t contain information of high value.

“When I began looking at the gene sequences in marsupials I quickly realised that even small things we discovered could be very significant,” she says. “Indeed, results from marsupial genomes were much more significant than sequences from a rat or a tiger because the marsupial genome was so far away from our own (and rats and tigers).

“Some scientists back then suggested that marsupial genomes will be so different that they’ll be worthless, that we won’t be able to make any meaningful comparisons. Ironically, other scientists suggested they would be too close, and that once again they wouldn’t be useful.

“However they were all wrong – the marsupial genome (and the platypus genome) are turning out to be ‘Goldilocks’ genomes. They’re not too close – for example, humans and mice are too close to make meaningful comparisons. And not too far away, humans and chickens are too far away to be usefully compared. But humans and kangaroos - and platypuses even more - are just the right distance apart from us to produce critically important insights on how the genomes work and have evolved.”

Graves’ passionate pursuit of the marsupial genome and the platypus genome has made her lab a world centre of comparative genomics, though she’s quick to point out they don’t limit themselves just to mammals.

“We’ve looked at the genomes of emus, snakes, frogs and even fish,” she says. “One area we’ve been following for a long time in comparing genomes is the genes connected with sex and sex chromosomes. This gives us a wonderful example of how genes can change in their function over time.

“One of the very exciting things to emerge from the platypus genome project is our finding that the platypus actually shares its sex chromosomes with birds. We think that’s probably what our sex chromosomes looked like 200 million years ago. But in the lineage that led to humans, we invented totally new sex chromosomes.”

Though Graves and her lab were part of the international effort to map the platypus genome, the actual sequencing work was funded and undertaken in the United States and paid for by the US National Institute of Health. She regrets that the first mapping of a genome of an Australian native animal was largely done overseas, and mourns Australia’s reluctance to invest in the expensive technologies of genome sequencing. As the technology becomes faster and cheaper hopefully this might change.

“Australia is really being left behind. This is a great time to be in comparative genomics, with many rich low hanging fruits to be harvested that will advance medical and agricultural advances, as well as fundamental understanding of genomes,” Graves says.

KanGO hopes to release results on the kangaroo genome later this year. As with the platypus, it’s expected there will be a wealth of new discoveries flowing from its release.

More information:

http://kangaroo.genomics.org.au