Escape of the BC200 gene to a human poxvirus reveals its persistent transposition in primates

Transposable elements mobilize within and occasionally between genomes, including from host to virus. We identified two insertions of the human BC200 noncoding RNA gene in the poxvirus molluscum contagiosum virus (MCV), which were likely acquired through long interspersed nuclear element 1 (LINE-1 or L1)–mediated retrotransposition during modern human history. Although BC200 was co-opted approximately 40 million years ago to regulate neuronal translation, we show that it never lost its mobilization capacity. Rather, BC200 functioned as a “master” source of L1-mediated germline retrotransposition events throughout anthropoid evolution, spawning hundreds of lineage-specific insertions. Additionally, BC200 has produced insertion polymorphisms segregating in the human population, including individual-specific insertions indicative of ongoing transposition activity. Thus, BC200 blurs the line between gene and transposon, combining stable function with persistent mobilization, including a recent escape into a human poxvirus.