Widespread distribution and structural diversity of Type IV IRESs in members of Picornaviridae.

Picornavirus genomes contain internal ribosomal entry sites (IRESs) that promote end-independent translation initiation. Five structural classes of picornavirus IRES have been identified, but numerous IRESs remain unclassified. Here, previously unrecognized Type IV IRESs were identified in members of three proposed picornavirus genera (Limnipivirus, Pasivirus, Rafivirus) and four recognized genera (Kobuvirus, Megrivirus, Sapelovirus, Parechovirus). These IRESs are ~230-420 nucleotides long, reflecting heterogeneity outside a common structural core. Closer analysis yielded insights into evolutionary processes that have shaped contemporary IRESs. The presence of related IRESs in diverse genera supports the hypothesis that they are heritable genetic elements that spread by horizontal gene transfer. Recombination likely also accounts for the exchange of some peripheral subdomains, suggesting that IRES evolution involves incremental addition of elements to a pre-existing core. Nucleotide conservation is concentrated in ribosome-binding sites, and at the junction of helical domains, likely to ensure orientation of subdomains in an active conformation.