Adaptive evolution of KoRV-A retroviral silencing in wild koalas [DNA-seq]. Adaptive evolution of KoRV-A retroviral silencing in wild koalas [DNA-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.

考拉逆转录病毒A（Koala Retrovirus-A）以自北向南的波状扩散态势在野生考拉种群中传播，同时转导生殖系，并在转变为内源性逆转录病毒的过程中诱导可遗传的遗传修饰。此前我们在布里斯班以南的考拉个体中发现，KoRV-A可在生殖系中表达，其产生的未剪接基因组转录本会被加工为有义链piwi相互作用RNA（piRNA），从而在转录后水平抑制病毒复制。本研究证实，这种初始的"先天"免疫应答在布里斯班河以南的考拉种群中普遍存在，但在该河以北的部分考拉亚群中，KoRV-A的启动子发生了甲基化，病毒的转录过程被沉默。转录沉默现象与MAP4K4基因的3'非翻译区（3'UTR）捕获反义KoRV-A前病毒相关。由此产生的融合转录本会被加工为反义链piRNA，进而在转录水平沉默生殖系中已整合的内源性逆转录病毒。该前病毒正在北部考拉种群中快速扩散，这表明其在KoRV-A转录沉默的适应性进化中发挥了直接作用。实验设计：为探究生殖系中逆转录病毒抑制的进化机制，我们开展了长读长与短读长DNA测序（DNA-seq）、RNA测序（RNA-seq）以及小RNA测序（small RNA-seq）。