Helping koalas to survive: world's largest koala pedigree genomic database aims to protect the population of the endangered species

An international research consortium with the participation of the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) is building the world's largest koala pedigree genomic database. This will help to improve the understanding and prevention of diseases, protect endangered koala populations, and thus ensure that koalas prosper everywhere in the long run. Among key challenges for these animals is the koala retrovirus (KoRV), which increases their susceptibility to bacterial infections, leukaemia and other types of cancer. All koalas in zoological gardens in North America and Europe as well as almost all free-ranging koalas in Australia carry this virus.

The San Diego Zoo Wildlife Alliance, the Californian research company Illumina, the University of Sydney, the Australian Museum Research Institute, the University of Nottingham, the Leibniz Institute for Zoo and Wildlife Research Berlin and the ZooParc de Beauval in France want to understand the health consequences of koala viruses and thus secure the long-term survival of the species. Almost all koalas – in their natural habitats in Australia as well as in zoological gardens – are naturally infected with one or more retroviruses, most notably the koala retrovirus (KoRV). In some koalas, these viral infections cause serious diseases such as cancer which endanger the entire population. Scientists from several biological and veterinary disciplines from around the world are working together to improve our understanding of KoRV. In order to know how retroviruses are transmitted and change from generation to generation, a research team led by the San Diego Zoo Wildlife Alliance in collaboration with the Leibniz-IZW investigated five generations of koalas at the San Diego Zoo and sequenced their genomes.

At the Leibniz-IZW, Prof Alex D. Greenwood, head of the Department of Wildlife Diseases, has been researching the retrovirus KoRV and its effects on the health of koalas for many years. “While we have learnt much about the integration of KoRV into the genomes of koala body cells and their impact on the health of wild koalas, we still don't really know how KoRV is transmitted from one generation to the next, how new integrations of KoRV into the koala genome arise and which integrations are most important for the health of koalas”, says Greenwood. Whole genomes of wild koalas have been sequenced, but information on both their ancestry and their health status is lacking. The San Diego Zoo Wildlife Alliance's Koala Genome Project aims to provide this new information.

The North American koala population in human care in zoological gardens was established between 1976 and 1981 with 14 koalas from Australia. More than 40 years later, the San Diego Zoo Wildlife Alliance cares for 30 koalas – the largest colony outside Australia. “The koalas in this investigation are part of one of the most comprehensive family trees in the world, with familial relationships reliably documented over decades of careful species maintenance and bio-banking”, says David Alquezar, Ph.D., Manager of the Australian Centre for Wildlife Genomics, Australian Museum Research Institute. “Interrogating KoRV integration data in this 'closed system' of related individuals provides a unique opportunity to explore KoRV mobility and to shed light on the impact of these integrations on disease occurrence and outcomes. This is particularly important for koala populations in human care, where there is a need to breed a reservoir of robust and healthy individuals on which to base future translocations.”

“Whether we can reduce the impact of KoRV-induced diseases on koala populations through testing and breeding programmes is a crucial question for the health and welfare of the animals”, says Dr Rachael Tarlinton from the University of Nottingham's School of Veterinary Medicine and Science. Most viruses are transmitted "horizontally" (between different individuals within a generation) by infection, so they are exogenous. They inject their genetic code into the somatic (non-reproductive) cells of the host organism and cause them to produce copies of the virus, which can then infect other host organisms. However, some viruses inject their genetic code directly into the germline cells of an organism, either sperm or egg cells. Once this happens, the viral DNA can become a permanent part of its host's genome: an endogenous virus that is not transmitted horizontally within a generation, but vertically from one generation to the next.

Vertical retrovirus transmission is a relatively common process, according to the scientists. All living organisms, including humans, have incorporated retroviral DNA as part of their own genome. For example, the remains of endogenous retroviruses make up eight per cent of the human genome. In most species, however, these viral integrations occurred millions of years ago and this part of their genome is now so degraded that it can no longer infect other hosts or cause health problems. The koala retrovirus – KoRV – is a special case. It has only begun its endogenization in the last 50,000 years. On an evolutionary timescale, this is practically yesterday, according to the scientists. Some of the KoRV subtypes are still exogenous and therefore far from being harmless. These subtypes sometimes cause serious health problems in koalas living in the wild and in human care.

“We don't know what happens to the host when a retrovirus is exogenous and initially becomes a relatively harmless fellow traveller”, says Alex Greenwood. “"We also don't know how the virus changes during this time to better adapt to the host, if it does at all.” Rachael Tarlinton adds: “In some cases these viruses are also beneficial for their hosts, changing gene expression and introducing new genetic diversity. We just don’t know how this process happens, or how quickly the changes to host and virus take to settle down.”

All koalas carry a high risk of cancer. Cora Singleton, head veterinarian at the San Diego Zoo Wildlife Alliance, explains: “Koalas are very good at hiding early stages of some cancers. They can appear normal one day and suddenly show a subtle change in behaviour the next. We examine their blood and bone marrow and then realize they have late-stage cancer, which progresses rapidly.” There is currently no adequate treatment for the affected koalas.

An international research consortium with the participation of the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) is building the world's largest koala pedigree genomic database. This will help to improve the understanding and prevention of diseases, protect endangered koala populations, and thus ensure that koalas prosper everywhere in the long run. Among key challenges for these animals is the koala retrovirus (KoRV), which increases their susceptibility to bacterial infections, leukaemia and other types of cancer. All koalas in zoological gardens in North America and Europe as well as almost all free-ranging koalas in Australia carry this virus.

The San Diego Zoo Wildlife Alliance, the Californian research company Illumina, the University of Sydney, the Australian Museum Research Institute, the University of Nottingham, the Leibniz Institute for Zoo and Wildlife Research Berlin and the ZooParc de Beauval in France want to understand the health consequences of koala viruses and thus secure the long-term survival of the species. Almost all koalas – in their natural habitats in Australia as well as in zoological gardens – are naturally infected with one or more retroviruses, most notably the koala retrovirus (KoRV). In some koalas, these viral infections cause serious diseases such as cancer which endanger the entire population. Scientists from several biological and veterinary disciplines from around the world are working together to improve our understanding of KoRV. In order to know how retroviruses are transmitted and change from generation to generation, a research team led by the San Diego Zoo Wildlife Alliance in collaboration with the Leibniz-IZW investigated five generations of koalas at the San Diego Zoo and sequenced their genomes.

At the Leibniz-IZW, Prof Alex D. Greenwood, head of the Department of Wildlife Diseases, has been researching the retrovirus KoRV and its effects on the health of koalas for many years. “While we have learnt much about the integration of KoRV into the genomes of koala body cells and their impact on the health of wild koalas, we still don't really know how KoRV is transmitted from one generation to the next, how new integrations of KoRV into the koala genome arise and which integrations are most important for the health of koalas”, says Greenwood. Whole genomes of wild koalas have been sequenced, but information on both their ancestry and their health status is lacking. The San Diego Zoo Wildlife Alliance's Koala Genome Project aims to provide this new information.

The North American koala population in human care in zoological gardens was established between 1976 and 1981 with 14 koalas from Australia. More than 40 years later, the San Diego Zoo Wildlife Alliance cares for 30 koalas – the largest colony outside Australia. “The koalas in this investigation are part of one of the most comprehensive family trees in the world, with familial relationships reliably documented over decades of careful species maintenance and bio-banking”, says David Alquezar, Ph.D., Manager of the Australian Centre for Wildlife Genomics, Australian Museum Research Institute. “Interrogating KoRV integration data in this 'closed system' of related individuals provides a unique opportunity to explore KoRV mobility and to shed light on the impact of these integrations on disease occurrence and outcomes. This is particularly important for koala populations in human care, where there is a need to breed a reservoir of robust and healthy individuals on which to base future translocations.”

“Whether we can reduce the impact of KoRV-induced diseases on koala populations through testing and breeding programmes is a crucial question for the health and welfare of the animals”, says Dr Rachael Tarlinton from the University of Nottingham's School of Veterinary Medicine and Science. Most viruses are transmitted "horizontally" (between different individuals within a generation) by infection, so they are exogenous. They inject their genetic code into the somatic (non-reproductive) cells of the host organism and cause them to produce copies of the virus, which can then infect other host organisms. However, some viruses inject their genetic code directly into the germline cells of an organism, either sperm or egg cells. Once this happens, the viral DNA can become a permanent part of its host's genome: an endogenous virus that is not transmitted horizontally within a generation, but vertically from one generation to the next.

Vertical retrovirus transmission is a relatively common process, according to the scientists. All living organisms, including humans, have incorporated retroviral DNA as part of their own genome. For example, the remains of endogenous retroviruses make up eight per cent of the human genome. In most species, however, these viral integrations occurred millions of years ago and this part of their genome is now so degraded that it can no longer infect other hosts or cause health problems. The koala retrovirus – KoRV – is a special case. It has only begun its endogenization in the last 50,000 years. On an evolutionary timescale, this is practically yesterday, according to the scientists. Some of the KoRV subtypes are still exogenous and therefore far from being harmless. These subtypes sometimes cause serious health problems in koalas living in the wild and in human care.

“We don't know what happens to the host when a retrovirus is exogenous and initially becomes a relatively harmless fellow traveller”, says Alex Greenwood. “"We also don't know how the virus changes during this time to better adapt to the host, if it does at all.” Rachael Tarlinton adds: “In some cases these viruses are also beneficial for their hosts, changing gene expression and introducing new genetic diversity. We just don’t know how this process happens, or how quickly the changes to host and virus take to settle down.”

All koalas carry a high risk of cancer. Cora Singleton, head veterinarian at the San Diego Zoo Wildlife Alliance, explains: “Koalas are very good at hiding early stages of some cancers. They can appear normal one day and suddenly show a subtle change in behaviour the next. We examine their blood and bone marrow and then realize they have late-stage cancer, which progresses rapidly.” There is currently no adequate treatment for the affected koalas.