How to make a koala

The koala genome provides clues to its evolution and will aid efforts to save it.

Yes the koala is cute. But it’s also evolved a bizarre survival strategy. Twenty million years ago when marsupial lions roamed the undergrowth, its ancestor sought refuge in the canopy of gum trees, spent most of its time sleeping and became the world’s only animal to survive solely on a diet of toxic gum leaves. Now the secret to this survival strategy has been revealed by reading its genome, an instruction manual written in 3.42 million letters of DNA and over 26,000 genes. The Australian-led international team reported the findings last July in Nature Genetics.

It’s not just Aussies who adore the cuddly koala. Phascolarctos cinereus, which translates to ‘ash grey pouched bear’, regularly makes the top 20 list of the world’s cutest animals. But it wasn’t always so. In the mid-19th century, an estimated 2.5 to 3 million were killed for the fur trade.

Now protected, the current population of about 329,000 animals ranges from Queensland down to NSW and Victoria, as well as the introduced populations of southeast Australia and its islands in Port Phillip Bay. The northern populations are considered at risk as the Eucalyptus forests they depend on are vulnerable to clearing, fragmentation and fire. On the other hand the population around Victoria is at risk from low genetic diversity since it was largely restored from small numbers of island animals. When genetic diversity is low, populations can be decimated by an infectious agent, a scenario dramatically playing out for Tasmanian devils as they battle devil facial tumour disease.

Reading the koala genome raised particular challenges. For starters, there was a problem sourcing high quality DNA. Koala blood proved unsuitable because it carried Dna-damaging chemicals such as phenolics. The only option was to use post-mortem tissue supplied by wildlife hospitals and zoos. But acquiring the tissue was just the first hurdle in this five year marathon.

Rebecca Johnson, a geneticist at the Australian museum who co-led the project, likens the task of reading the koala genome to shredding eight volumes of an encyclopaedia written in ancient Sanskrit and putting them back together again. Shredding is needed to feed bits of DNA code into sequencing machines. Putting it back together is tough because most of the bits look similar. However, the longer the shreds, the more confidence that the final assembly is correct. The team were able to use longer shreds thanks to state-of-theart ‘third generation’ DNA sequencing machines which can tolerate being fed ‘longer reads’. The koala genome is the first to be sequenced in Australia using this technology. So how does a genome help koalas? First, the genome has allowed researchers to assess the diversity of the country wide population. The good news is the northern population is more diverse than thought. Furthermore, even though northern koalas are smaller, paler and fluffier than the southerners, the population shows small continuous variations, defining it as a single species. And that should reopen the debate about mixing the inbred southern populations with fresh northern blood. “It’s time to have tough conversations,” says Katherine Belov, the University of Sydney geneticist who co-led the project.

Revealing the secrets of the koala’s weird biology will also be good for their health. Koalas are ravaged by chlamydia, a sexually transmitted disease that can be passed to offspring and causes blindness and infertility.

Vets treating the disease with common antibiotics like chloramphenicol find they need to use massive doses. Now thanks to a collaboration with researchers at the Earlham Institute in Norwich in the UK, they know why.

Compared to other animals, koalas are kitted out with a huge and diverse set of detoxifying ‘ P450’ genes. They are vital to the koala’s ability to survive solely on gum leaves which are packed with toxic terpenes. But P450 genes also break down antibiotics. Understanding how koalas detoxify chemicals should help inform which kinds of drugs will work best for them.

Koalas are also notorious for being picky eaters, a great challenge for zoo keepers who need to supply each one with over one kg of eucalyptus leaves each day. That pickiness has now been traced to their large collection of genes for smelling and tasting bitter chemicals.

Another revelation from the koala genome sheds light on their distinctly marsupial type of immune system. Like all marsupials, koalas are born at an extremely early stage of development. About the size of a kidney bean, the newborn is devoid of organs or an immune system. Immunity is provided by peptide molecules secreted in the mother’s milk. They are so effective, koala joeys do not suffer infections after surgery, says Belov. While other marsupials contain only two sets of these genes, the koala genome boasts five. Belov plans to test the antimicrobial activity of the newly identified genes by making the peptides in a test tube. So far, one of them fights golden staph and with the rise of antibiotic resistance, she says “it’s a great opportunity to develop new drugs”.

Indeed no letter of this ancient text will go unscrutinised. For La Trobe University geneticist Jenny Graves, the koala genome will help in her quest to trace the evolution of sex chromosomes. And she says: “I would still like to find the gene for cuteness”.