Multi-generational koala pedigree analysis reveals rapid changes in heritable provirus load associated with life history traits.

Retroviruses that colonize the host germline can be passed on as inherited genetic variants. The koala (Phascolarctos cinereus) is currently experiencing germline colonization by two retroviruses, the koala retrovirus (KoRV) and phaCin-β. We analyze the integration site segregation and diversity of endogenous KoRV, phaCin-β, and the related phaCin-β-like in 111 pedigreed koalas from the San Diego Zoo Wildlife Alliance and seven European Zoos. The use of multigenerational pedigrees and the inclusion of health information for each individual koala reveal elimination of retroviruses from proto-oncogenes and the generation and spread of new germline integrations. Seven-hundred-and-fourteen integrations do not persist in the living population. For the 55 triads examined, 21 unique integrations identified in individual koalas are absent in their parents. Retroviral integrations associated with leukemia, fertility, and longevity are used to estimate genetic risk scores and develop a longevity breeding index to minimize neoplasia risk in the captive koala population.