Adaptive evolution of KoRV-A  retroviral silencing in wild koalas [RNA-seq]
Koala Retrovirus-A is spreading through wild koalas in a north to south wave while transducing the germline, generating heritable genetic modifications as it transitions to an endogenous retrovirus.  In animals south of Brisbane, we previously found that KoRV-A is expressed in the germline, but the resulting unspliced genomic transcripts are processed into sense strand piRNAs, post-transcriptionally suppressing replication.   Here we show that this initial “innate” response is prevalent in animals south of the Brisbane River, but KoRV-A promoters are methylated and the virus is transcriptionally silenced in a subpopulation of animals north of the river.  Transcriptional silencing correlates with capture of an anti-sense KoRV-A provirus by the 3'UTR of the MAP4K4 gene.  The resulting hybrid transcripts are processed into anti-sense piRNAs, which transcriptionally silence established endogenous retroviruses in the germline.  This provirus is sweeping through northern koalas, supporting a direct role in adaptive evolution of KoRV-A transcriptional silencing. Overall design: To investigate the evolution of retroviral repression in the germline, we performed long- and short-read DNA-seq, RNA-seq, and small RNA-seq.