How to make a koala

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

Cosmos - - Digest -

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”.

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