The San Diego Zoo is internationally renowned for its commitment to wildlife conservation and is home to the largest population of koalas outside of Australia. One significant challenge facing their koala community is the prevalence of koala retrovirus (KoRV), which is associated with various fatal conditions such as susceptibility to bacterial infections, leukemia, lymphoma, and other cancers. Surprisingly, 100% of koalas in North America, as well as those in the Australian states of Queensland and New South Wales, carry this virus. Even in Victoria, between 15% and 70% of koalas are affected.
The unique aspect of KoRV lies in its transmission. Unlike common horizontally transmitted viruses that infect organisms through infection, KoRV can become endogenous by integrating its genetic code into an organism's germline (reproductive) cells, such as sperm or eggs. This integration results in the viral DNA becoming a permanent part of the host's genome, transmitted vertically from one generation to the next.
While this may sound alarming, the presence of retroviral DNA in living organisms is not uncommon. In fact, all living organisms have accumulated retroviral DNA as a natural part of their genetic makeup. In most species, these viral integrations occurred millions of years ago, and the DNA has degraded to a point where it no longer poses a threat of infecting other hosts or causing health problems. This natural process ensures the elimination of viruses that could harm their hosts.
Despite this common occurrence, there is still much to learn about the transition of a retrovirus from being exogenous to becoming a relatively harmless part of a host's genome. The details of how the virus changes, if at all, during this transition and how it adapts to the host remain unknown. Researchers, such as Alex Greenwood from the Leibniz Institute for Zoo and Wildlife Research and Rachael Tarlinton from the University of Nottingham, emphasize the need to understand this process better, as some retroviruses may even be beneficial to their hosts by influencing gene expression and introducing new genetic diversity. However, the specific mechanisms and timelines of these changes remain elusive.
Koalas face potential threats due to the Koala Retrovirus (KoRV), a relatively recent phenomenon that began about 50,000 years ago in evolutionary terms. Unlike KoRV subtype A, which has become endogenous in koalas, subtypes B, C, and others remain exogenous, contributing to serious health issues. The San Diego Zoo has adapted its care and breeding practices to prevent the spread of these exogenous subtypes.
Utilizing the fact that koalas are naturally solitary and sleep extensively, the zoo manages genetic diversity through meticulous record-keeping of mean kinship. Female koalas are introduced to suitable males one at a time to control breeding. While they can have eight to 10 offspring during their 12 to 14-year lifespan, infertility due to chlamydia is a concern among wild koalas. The zoo's vigilant breeding management has successfully kept their population free of this infection.
Despite these efforts, koalas remain highly susceptible to cancer, which often progresses rapidly and is challenging to treat once detected. KoRV is linked to these health issues, although more genomic research is needed to establish a definitive connection. The iConserve koala retrovirus sequencing project, initiated in 2023, aims to address this gap by conducting longitudinal studies across multiple koala generations.
The San Diego Zoo's extensive genetic samples, spanning five generations and dating back to the 1970s, provide valuable data for the project. Illumina performed whole-genome sequencing on these samples, creating the largest pedigree of any koala genomic database to date. The information gathered through this project is expected to shed light on the genetic causation of koala health conditions, facilitating better management and conservation strategies for these iconic marsupials.
The research aims to correlate known causes of death in the zoo's pedigree with KoRV integration patterns identified in the sequencing data. This comparison will help determine the strength of the association between specific integration sites and adverse health outcomes in koalas. For instance, if certain KoRV integration patterns are linked to specific cancers in past koalas, it may enable predictions about which koalas in the future are at a higher risk of developing these cancers. Such insights are crucial for wildlife care specialists when planning optimal breeding pairs.
The findings from this study will not only guide breeding decisions within the zoo but will also influence management strategies for wild koala populations. With their natural habitat facing significant fragmentation, exacerbated by recent bushfires in Australia, disconnected koala populations experience reduced genetic diversity and increased vulnerability to diseases. Conservation efforts may involve strategically translocating specific animals to enhance genetic diversity and avoid introducing new KoRV subtypes to previously unaffected populations.
The potential discovery of associations between retroviral integration sites and immunological genes holds great promise for research. Understanding the mechanisms of KoRV endogenization and its impact on disease development is particularly intriguing given the rarity of such a virus undergoing this process. This knowledge could significantly contribute to koala health and play a vital role in their conservation efforts.
The scientific community has debated the intervention in the gradual and likely inevitable process of KoRV endogenization, considering the prevalence of retroviral DNA in animal genomes. However, participants in the iConserve study acknowledge a collective responsibility in this case, recognizing the importance of understanding and addressing the implications of KoRV endogenization for the well-being and conservation of koalas.
“Yes, it is a natural process,” said Higgins, “but it’s going on in an unnatural environment and context that humans are causing. It’s up to us to create an environment where that natural process can unfold. From an evolutionary perspective, it’s hard to adapt to something if you’ve got all these other pressures. We’re identifying which populations are most at risk and focusing on removing other risks to allow them to cope.”
“Over time, we expect the koala to adapt to this endogenizing virus. Until this happens, koalas are threatened by KoRV as well as by habitat loss and fragmentation. We can’t eliminate KoRV from koalas, but we can preserve and protect the healthy ecosystems that they need to survive,” said Singleton.
At the time of this update, the sequencing phase of the project has concluded, and Guilherme Neumann, a postdoctoral bioinformatician at the Leibniz Institute, has successfully identified over 1500 KoRV insertions within the 91 sequenced animals.
As anticipated for a relatively small zoo population, these koalas exhibit a higher degree of shared KoRV integration sites compared to their counterparts in the wild. According to Greenwood, the next intriguing phase will involve determining if these shared integrations predominantly occur in genome regions with minimal harm. If so, the focus will shift to the less widely shared integrations, which might harbor more problematic KoRV integrations. These specific sites could become potential targets for future management strategies.
Simultaneously, Singleton expresses optimism about the potential transformative impact of this research on koala conservation efforts.
“We’ve known for many years that we have something really special in the data from the North American koala population, but we haven’t been able to access the technology to analyze it,” she says. “Through our partnership with Illumina, we are achieving research objectives that seemed unreachable back in 2021. Bringing together this international team, learning from our koala population to help koalas in their native range, is a career pinnacle for me as a zoo veterinarian.”
The unique aspect of KoRV lies in its transmission. Unlike common horizontally transmitted viruses that infect organisms through infection, KoRV can become endogenous by integrating its genetic code into an organism's germline (reproductive) cells, such as sperm or eggs. This integration results in the viral DNA becoming a permanent part of the host's genome, transmitted vertically from one generation to the next.
While this may sound alarming, the presence of retroviral DNA in living organisms is not uncommon. In fact, all living organisms have accumulated retroviral DNA as a natural part of their genetic makeup. In most species, these viral integrations occurred millions of years ago, and the DNA has degraded to a point where it no longer poses a threat of infecting other hosts or causing health problems. This natural process ensures the elimination of viruses that could harm their hosts.
Despite this common occurrence, there is still much to learn about the transition of a retrovirus from being exogenous to becoming a relatively harmless part of a host's genome. The details of how the virus changes, if at all, during this transition and how it adapts to the host remain unknown. Researchers, such as Alex Greenwood from the Leibniz Institute for Zoo and Wildlife Research and Rachael Tarlinton from the University of Nottingham, emphasize the need to understand this process better, as some retroviruses may even be beneficial to their hosts by influencing gene expression and introducing new genetic diversity. However, the specific mechanisms and timelines of these changes remain elusive.
Koalas face potential threats due to the Koala Retrovirus (KoRV), a relatively recent phenomenon that began about 50,000 years ago in evolutionary terms. Unlike KoRV subtype A, which has become endogenous in koalas, subtypes B, C, and others remain exogenous, contributing to serious health issues. The San Diego Zoo has adapted its care and breeding practices to prevent the spread of these exogenous subtypes.
Utilizing the fact that koalas are naturally solitary and sleep extensively, the zoo manages genetic diversity through meticulous record-keeping of mean kinship. Female koalas are introduced to suitable males one at a time to control breeding. While they can have eight to 10 offspring during their 12 to 14-year lifespan, infertility due to chlamydia is a concern among wild koalas. The zoo's vigilant breeding management has successfully kept their population free of this infection.
Despite these efforts, koalas remain highly susceptible to cancer, which often progresses rapidly and is challenging to treat once detected. KoRV is linked to these health issues, although more genomic research is needed to establish a definitive connection. The iConserve koala retrovirus sequencing project, initiated in 2023, aims to address this gap by conducting longitudinal studies across multiple koala generations.
The San Diego Zoo's extensive genetic samples, spanning five generations and dating back to the 1970s, provide valuable data for the project. Illumina performed whole-genome sequencing on these samples, creating the largest pedigree of any koala genomic database to date. The information gathered through this project is expected to shed light on the genetic causation of koala health conditions, facilitating better management and conservation strategies for these iconic marsupials.
The research aims to correlate known causes of death in the zoo's pedigree with KoRV integration patterns identified in the sequencing data. This comparison will help determine the strength of the association between specific integration sites and adverse health outcomes in koalas. For instance, if certain KoRV integration patterns are linked to specific cancers in past koalas, it may enable predictions about which koalas in the future are at a higher risk of developing these cancers. Such insights are crucial for wildlife care specialists when planning optimal breeding pairs.
The findings from this study will not only guide breeding decisions within the zoo but will also influence management strategies for wild koala populations. With their natural habitat facing significant fragmentation, exacerbated by recent bushfires in Australia, disconnected koala populations experience reduced genetic diversity and increased vulnerability to diseases. Conservation efforts may involve strategically translocating specific animals to enhance genetic diversity and avoid introducing new KoRV subtypes to previously unaffected populations.
The potential discovery of associations between retroviral integration sites and immunological genes holds great promise for research. Understanding the mechanisms of KoRV endogenization and its impact on disease development is particularly intriguing given the rarity of such a virus undergoing this process. This knowledge could significantly contribute to koala health and play a vital role in their conservation efforts.
The scientific community has debated the intervention in the gradual and likely inevitable process of KoRV endogenization, considering the prevalence of retroviral DNA in animal genomes. However, participants in the iConserve study acknowledge a collective responsibility in this case, recognizing the importance of understanding and addressing the implications of KoRV endogenization for the well-being and conservation of koalas.
“Yes, it is a natural process,” said Higgins, “but it’s going on in an unnatural environment and context that humans are causing. It’s up to us to create an environment where that natural process can unfold. From an evolutionary perspective, it’s hard to adapt to something if you’ve got all these other pressures. We’re identifying which populations are most at risk and focusing on removing other risks to allow them to cope.”
“Over time, we expect the koala to adapt to this endogenizing virus. Until this happens, koalas are threatened by KoRV as well as by habitat loss and fragmentation. We can’t eliminate KoRV from koalas, but we can preserve and protect the healthy ecosystems that they need to survive,” said Singleton.
At the time of this update, the sequencing phase of the project has concluded, and Guilherme Neumann, a postdoctoral bioinformatician at the Leibniz Institute, has successfully identified over 1500 KoRV insertions within the 91 sequenced animals.
As anticipated for a relatively small zoo population, these koalas exhibit a higher degree of shared KoRV integration sites compared to their counterparts in the wild. According to Greenwood, the next intriguing phase will involve determining if these shared integrations predominantly occur in genome regions with minimal harm. If so, the focus will shift to the less widely shared integrations, which might harbor more problematic KoRV integrations. These specific sites could become potential targets for future management strategies.
Simultaneously, Singleton expresses optimism about the potential transformative impact of this research on koala conservation efforts.
“We’ve known for many years that we have something really special in the data from the North American koala population, but we haven’t been able to access the technology to analyze it,” she says. “Through our partnership with Illumina, we are achieving research objectives that seemed unreachable back in 2021. Bringing together this international team, learning from our koala population to help koalas in their native range, is a career pinnacle for me as a zoo veterinarian.”