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The trajectory of KoRV-A Evolution Indicates Initial Integration into the Koala Germline Genome Near Coffs Harbour [Adelaide DNA-seq]

ABSTRACT: Koala Retrovirus-A is a gamma-retrovirus sweeping wild koalas via a combination of horizontal and vertical transfer, contributing substantial genomic diversity across and even within koala populations. While studies have estimated KoRV-A's integration into the koala genome occurred 120–50,000 years ago, the origin and spread patterns of its endogenization remain unclear. Here, we analyze KoRV-A germline insertions using whole-genome sequencing data from 405 wild koalas, encompassing nearly the full koala habitat range. We map a trajectory of KoRV-A evolution and propose that KoRV-A first entered the koala germline genome near Coffs Harbour. As KoRV-A spread, replication-competitive subtypes emerged, two of which recombined with an ancient endogenous retrovirus, PhER, resulting in distinct recombination variants across northern and southern koala populations. Additionally, we identified a geographic barrier north of Sydney, which has slowed the southward spread of KoRV-A into Sydney and beyond.

ORGANISM(S): Phascolarctos cinereus

PROVIDER: GSE282117 | GEO | 2025/01/15

REPOSITORIES: GEO

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Project description:Production of milk is a key characteristic of mammals, but the features of lactation vary greatly between monotreme, marsupial and eutherian mammals. Marsupials have a short gestation followed by a long lactation period, and the milk constituents vary greatly across lactation to meet the changing needs of the developing young. Marsupials are born immunologically naïve and rely on their mother’s milk for immunological protection. The koala is an iconic Australian species and many are increasingly threatened by disease. Here we use a mammary transcriptome, two milk proteomes and the koala genome to comprehensively characterise the protein components of the milk of the koala, with a key focus on the immune constituents during early and late lactation. We have characterised the most abundant peptides present in milk, examined key differences between early and late lactation, and determined differences between the koala and other marsupial species. The most abundant proteins were well characterised mammalian and marsupial-specific milk proteins including β-lactoglobulin, lactotransferrin, caseins and early lactation protein. We have generated a list of 851 immune compounds identified in the mammary transcriptome and examined a range of immune proteins that were highly abundant in the milk proteomes. These include immunoglobulins, complement components and immune receptors. A host of antimicrobial peptides were identified including cathelicidins, lysozyme, WAP four-disulfide core domain protein 2, Mucin-1 and Peptidoglycan recognition protein. We discovered that the previously described marsupial milk protein Very Early Lactation Protein is an ortholog of the eutherian gene Glycam1 (PP3) and likely has an antimicrobial role in milk. We also identified highly abundant koala endogenous retrovirus sequences in the mammary and milk transcriptome and proteomes, identifying a potential route for retroviral transmission from mother to young. Identifying and characterising the immune components of milk is key to understanding how marsupial young are protected throughout lactation and the novel immune compounds identified may have applications in clinical research.

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The trajectory of KoRV-A Evolution Indicates Initial Integration into the Koala Germline Genome Near Coffs Harbour [Adelaide DNA-seq]

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