Dynamic evolution of retroviral envelope-derived sequences in primates

It is known that several endogenous retroviruses, remnants of ancient retroviral integrations, retain envelope (env) genes encoding fusogenic proteins in primates. Whilst most env genes are degraded, a few have been co-opted by hosts, yet the entire evolutionary dynamics of env sequences remain poorly understood. To explore this, we screened and compared env open reading frames (ORFs) from 247 primate genomes. In total, 8683 nearly intact env-ORFs encoding 400 or more amino acids were identified, and their copy numbers ranged from 3 to 429 across primate species. Sequence similarity clustering revealed a clear evolutionary signature that distinguishes the small set of long-term co-opted env-derived genes, which are retained at low copy numbers across lineages, from the broader pool of rapidly turning-over env-ORFs. Applying this framework, we identified a previously unrecognized, single-copy env ortholog conserved across Tarsiiformes, named env-Tar1, and experimentally demonstrated its cell fusion activity in vitro, providing the first functional evidence of an env-derived gene co-opted in a tarsier lineage. Further, we found that certain co-opted env-derived genes may have lost their functions due to nonsense or indel mutations within specific primate lineages. Considering that many env genes tend to be maintained at low copy numbers and are reported to be under purifying selection, such dynamic evolutionary turnover of env-derived genes may be driven by host-virus arms races, as viruses and endogenous retroviruses often share cell-surface receptors.