Purging of deleterious retroviral integrations at the earliest stages of genomic invasion

• Applicant: Professor Alex Greenwood, Ph.D.
• Subject Area: Evolutionary Cell and Developmental Biology (Zoology) ; Evolution, Anthropology
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 429450856

• Final Report Year: 2024

Final Report Abstract

The project sought to determine if we could detect the accelerated effects of natural selection on an island population of koalas derived from very few starting individuals and with no exchange of individuals between the mainland and the island for over 100 years. The results suggest that the koala share exceptionally few koala retrovirus (KoRV) integrations with mainland populations and share many distinct integrations with other koalas on the island. The integration profiles in genes differ between St. Bees and the mainland suggesting integrations have been selected for those with less deleterious effects on the koalas. The statistical tests for this are underway as we search for evidence for deviation from Hardy-Weinberg Equilibrium showing either too many or too few heterozygous individuals on St. Bees compared to more outbread or other inbred (e.g. zoo koala) populations. We also clearly show that the main driving selective force on KoRV integrations is their preferential integration and dysregulation of oncogenes which lead to excessively high levels of neoplasia in koalas where KoRV is abundant in the genome.

Publications

• Retroviral integrations contribute to elevated host cancer rates during germline invasion. Nature Communications, 12(1).
  McEwen, Gayle K.; Alquezar-Planas, David E.; Dayaram, Anisha; Gillett, Amber; Tarlinton, Rachael; Mongan, Nigel; Chappell, Keith J.; Henning, Joerg; Tan, Milton; Timms, Peter; Young, Paul R.; Roca, Alfred L. & Greenwood, Alex D.
  
• Genome Reference Assembly for Bottlenecked Southern Australian Koalas. Genome Biology and Evolution, 15(1).
  Blanchard, Adam Mark; Emes, Richard David; Greenwood, Alex David; Holmes, Nadine; Loose, Matthew William; McEwen, Gail Katherine; Meers, Joanne; Speight, Natasha & Tarlinton, Rachael Eugenie
  
• The role of koala retrovirus integrations in promoting neoplasia in koalas (Phascolarctos cinereus). In Proceedings of the Second Koala Retrovirus Workshop, ed. D. E. Alquezar-Planas, D. P. Higgins, C. L. Singleton, and A. D. Greenwood. Technical Reports of the Australian Museum online, 38, 31-34.
  McEwen, Gayle & Greenwood, Alex D.
  
• Wildlife endogenous retroviruses: colonization, consequences, and cooption. Trends in Genetics, 40(2), 149-159.
  Jern, Patric & Greenwood, Alex D.