Unexpected Discovery and Expression of Amphibian Class II Endogenous Retroviruses

Endogenous retroviruses (ERVs) are the remnants of past retroviral infections. Fossil records of class II retroviruses have been discovered in a range of vertebrates, with the exception of amphibians, which are known only to possess class I and class III-like ERVs. Through genomic mining of all available amphibian genomes, we identified, for the first time, class II ERVs in amphibians. The class II ERVs were found only in Gymnophiona (caecilians) and not in the genomes of the other amphibian orders, Anura (frogs and toads) and Caudata (salamanders and newts), which are phylogenetically closely related. Therefore, the ERV endogenization occurred after the split of Gymnophiona, Anura, and Caudata (323 million years ago). Investigation of phylogenetic relationship and genomic structure revealed that the ERVs may originate from alpha- or betaretroviruses. We offer evidence that class II ERVs infiltrated amphibian genomes recently and may still have infectious members. Remarkably, certain amphibian class II ERVs can be expressed in diverse tissues. This discovery closes the major gap in the retroviral fossil record of class II ERVs and provides important insights into the evolution of class II ERVs in vertebrates.IMPORTANCE Class II retroviruses, largely distributed among mammals and birds, are of particular importance for medicine and economics. Class II ERVs have been discovered in a range of vertebrates, with the exception of amphibians, which are known only to possess class I and class III-like ERVs. Here, for the first time, we discovered class II ERVs in amphibians. We also revealed that the ERVs may originate from alpha- or betaretroviruses. We revealed that class II ERVs were integrated into amphibian genomes recently and certain amphibian class II ERVs can be expressed in diverse tissues. Our discovery closes the major gap in the retroviral fossil record of class II ERVs, and also indicates that amphibians may be still infected by class II retroviruses.