Evolution of KoRV-A transcriptional silencing in wild koalas.

Koala retrovirus-A (KoRV-A) is spreading through wild koalas in a north-to-south wave while transducing the germ line, modifying the inherited genome as it transitions to an endogenous retrovirus. Previously, we found that KoRV-A is expressed in the germ line, but unspliced genomic transcripts are processed into sense-strand PIWI-interacting RNAs (piRNAs), which may provide an initial "innate" form of post-transcriptional silencing. Here, we show that this initial post-transcriptional response is prevalent south of the Brisbane River, whereas KoRV-A expression is suppressed, promoters are methylated, and sense and antisense piRNAs are equally abundant in a subpopulation of animals north of the river. These animals share a KoRV-A provirus in the MAP4K4 gene's 3' UTR that is spreading through northern koalas and produces hybrid transcripts that are processed into antisense piRNAs, which guide transcriptional silencing. We speculate that this provirus triggers adaptive transcriptional silencing of KoRV-A and is sweeping to fixation.