Evolution and Genetic Diversity of the Retroviral Envelope in Anamniotes

Abstract Retroviruses are widely distributed in all vertebrates, as are their endogenous form, endogenous retrovirus (ERV), which serves as “fossil” evidence to trace the ancient origins and history of virus-host interactions over millions of years. The retroviral envelope (Env) plays a significant role in host range determination, but major information on genetic diversification in anamniotes is lacking. Here, by incorporating multiple-round in silico similarity search and phylogenomic analysis, 25498 ERVs with gamma-type Env (GTE), covalently associated Env, were discovered by searching against all 974 available fish and 19 amphibian genomes, but no beta-type Env (BTE), noncovalently associated Env, were found. Furthermore, a nine-type classification system of anamniote GTE was proposed by combining phylogenetic and domain/motif analyses. The elastic genomic organization and overall phylogenetic incongruence between anamniotic Env and its neighboring polymerase (Pol) implied that early retroviral diversification in anamniotic vertebrates was facilitated by frequent recombination. At last, host opioid growth factor receptor (OGFr) gene capturing by anamniotic ERVs with GTE was reported for the first time. Overall, our findings overturn traditional Pol genotyping and reveal a complex evolutionary history of anamniotic retroviruses inferred by Env evolution. Author summary Although the retroviral envelope (Env) protein in amniotes has been well studied, its evolutionary history in anamniotic vertebrates is ambiguous. By analyzing more than 25000 ERVs with gamma-type Env (GTE) in anamniotes, several important evolutionary features were identified. First, GTE were found to be widely distributed among different amphibians and fish. Second, nine types of GTE were discovered, revealing the great genetic diversity. Third, GTE-containing ERVs have rampantly proliferated in certain amphibians such as Ambystoma mexicanum , and the copy number was found to be markedly higher than 10000. Fourth, the incongruence between the Env and Pol phylogenies suggested that frequent recombination shaped the early evolution of anamniote retroviruses. Fifth, an ancient horizontal gene transfer event was discovered from anamniotes to ERVs with GTE. These findings reveal a complex evolution pattern for retroviral Env in anamniotes.