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

## TL;DR

This study tracks retrovirus integration in koalas over generations, linking it to health traits and informing breeding strategies to reduce cancer risk.

## Contribution

The study introduces a genetic risk scoring system for retrovirus-related traits in koalas using multigenerational pedigree data.

## Key findings

- Retroviral integrations associated with leukemia, fertility, and longevity were identified.
- 21 unique integrations in koalas were absent in their parents, indicating new germline integrations.
- A longevity breeding index was developed to minimize neoplasia risk in captive koalas.

## Abstract

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.

Koala retroviruses are models of transposable element colonization of germlines. By mapping their integration sites in koala pedigrees, this study provides genetic risk scoring for breeding decisions and documents rates of acquisition and loss of retroviral integrations across generations.