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Koala genome sequenced for first time

3 July 2018
Antimicrobial peptides found in milk to help tiny joeys at birth
Sydney has led the world-first sequencing of the koala genome in a global consortium spanning 54 scientists in 29 organisations. It will inform conservation efforts - from diet to genetic diversity - of our iconic marsupial.

A team of Australian and international scientists led by Adjunct Professor and Australian Museum Research Institute director Rebecca Johnson and Professor Katherine Belov at the University of Sydney, has completed the world-first full sequencing of the koala genome.

Considered to be the most complete marsupial genome sequenced to date, it is in terms of quality, on par with the human genome. The highly accurate genomic data will provide scientists with new information that will inform conservation efforts, aid in the treatment of diseases and help to ensure the koala’s long-term survival.

The genetic blueprint has not only unearthed a wealth of data regarding the koalas unusual and highly specialised diet of eucalyptus leaves, but also provides important insights into their immune system, population diversity and the evolution of koalas.

The Australian-led consortium of scientists comprised 54 scientists from 29 different institutions across seven countries. They have sequenced over 3.4 billion base pairs and more than 26,000 genes in the koala genome, which makes it slightly larger than the human genome. 

The findings are published today in Nature Genetics.

Professor Katherine Belov and Adjunct Professor Rebecca Johnson and friend

Professor Katherine Belov and Adjunct Professor Rebecca Johnson

Co-lead author at the University of Sydney, Professor of Comparative Genomics, Katherine Belov said: “The genome provides a springboard for the conservation of this biologically unique species.”

Professor Belov, from the School of Life and Environmental Sciences, said an important discovery was the characterisation of the composition of koala milk. They are born without an immune system after 34-36 days gestation and spend about six months developing in the pouch.

“We characterised the main components of the mothers’ milk – which is crucial for koala joeys – born the size of a jellybean and weighing half of one gram,” Professor Belov said. 

"We identified genes that allow the koala to fine-tune milk protein composition across the stages of lactation, to meet the changing needs of their young.

“Thanks to the high-quality genome, the team was able to analyse and discover koala-specific milk proteins that are critical for various stages of development.

"It also appears these proteins may have an antimicrobial role, showing activity against a range of bacterial and fungal species, including Chlamydia pecorum, the strain known to cause ocular and reproductive disease in koalas,” she said.

Chlamydia, which causes infertility and blindness, has severely impacted koala populations in New South Wales and Queensland.  Using information gained from the koala genome, scientists hope to develop a vaccine to fight diseases like chlamydia.

University of the Sunshine Coast Professor Peter Timms said another major infection threatening the species was koala retrovirus (KoRV), however very little was known about it.

"The complete koala genome has been instrumental in showing that an individual koala can have many (more than a hundred) insertions of KoRV into its genome, including many versions of KoRV,” Professor Timms said.

Professor Jennifer Graves, AO, Distinguished Professor of Genetics, La Trobe University and winner of the 2017 Prime Minister's Prize for Science, said: “We could never have imagined, when we were pioneering koala genetics in the 1980s, that one day we’d have the entire koala genome sequence.”

The Koala Genome Consortium announced the establishment of the project in 2013 with its first unassembled draft genome. The collective aim was to steer their research towards ensuring the long-term survival of this important marsupial while simultaneously increasing Australia’s genomics capability.

Since then, researchers have worked tirelessly to assemble this genome into the most complete and accurate marsupial genome to date and annotate its 26,000 genes for analysis. The koala genome has been sequenced to an accuracy of 95.1 percent, which is comparable to that of the human genome.

The 3.4 billion base pairs of the published koala genome were sequenced at the Ramaciotti Centre for Genomics, at the University of New South Wales, using new sequencing technology.

UNSW Professor Marc Wilkins, director of the Ramaciotti Centre for Genomics, said: “We then assembled the genome with supercomputers, allowing the Consortium to then study the 20,000+ genes of this unique species.” 

Consortium members from the Earlham Institute (EI) in Norwich, United Kingdom, identified that koalas have two large expansions in a gene family known to be integral to detoxification, the Cytochrome P450 gene family of metabolic enzymes. They found these genes to be expressed in many koala tissues, particularly in the liver; indicating they have a very important function in detoxification and likely allowed koalas to become dietary specialists.

Dr Will Nash in the Haerty Group at Earlham Institute, said: “Gene duplication can lead to copies of genes associated with specific functions being retained in the genome. In the koala, the largest group of retained copies make an enzyme that breaks down toxins.

"This means the koala has evolved an excellent toolkit to deal with eating highly toxic eucalypts, one made up of lots of copies of the same (or very similar) tools.”

One of the most threatening processes to koala survival is loss of habitat through land clearing and urbanisation, which results in a reduction of habitat connectivity, reduced genetic diversity and puts koalas at high risk of inbreeding. The results of inbreeding can be highly detrimental to survival of those koala populations as it leads to reduced genetic diversity.

Professor Johnson, a University of Sydney alumnus BSc (Hons) Genetics 1995, said koala numbers had plummeted in northern parts of its range since European settlement but had increased in some southern parts.

"The uneven response of koala populations throughout their range is one of the major challenges facing broad scale management of the species,” she said.

“For the first time, using over 1000 genome linked markers, we are able to show that NSW and QLD populations show significant levels of genetic diversity and long-term connectivity across regions.” 

This genomic sequencing represents the new generation of science-based conservation policy as it has already been integrated as an important pillar into the NSW Koala Strategy 2018.

All of the sequence data generated by The Koala Genome Consortium has been deposited into public databases and made freely available to scientists around the world. 

The koala's unique and highly specific diet of eucalyptus (gum) tree leaves, has resulted in koalas being especially vulnerable to habitat loss due to the clearing of native vegetation for agriculture and urban development.  The federal government lists koala populations in Queensland, New South Wales and Australian Capital Territory as "Vulnerable" under national environment law.

Professor Johnson concluded: “Our next efforts must be in the application of these findings to genetically manage koala populations, advance the treatment of the diseases affecting koalas, with the goal of conserving this very important species."

Vivienne Reiner

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