Viral Proteins Originated De Novo by Overprinting Can Be Identified by Codon Usage: Application to the “Gene Nursery” of Deltaretroviruses

Abstract

A well-known mechanism through which new protein-coding genes originate is by modification of pre-existing genes, e.g. by duplication or horizontal transfer. In contrast, many viruses generate protein-coding genes de novo, via the overprinting of a new reading frame onto an existing (“ancestral”) frame. This mechanism is thought to play an important role in viral pathogenicity, but has been poorly explored, perhaps because identifying the de novo frames is very challenging. Therefore, a new approach to detect them was needed. We assembled a reference set of overlapping genes for which we could reliably determine the ancestral frames, and found that their codon usage was significantly closer to that of the rest of the viral genome than the codon usage of de novo frames. Based on this observation, we designed a method that allowed the identification of de novo frames based on their codon usage with a very good specificity, but intermediate sensitivity. Using our method, we predicted that the Rex gene of deltaretroviruses has originated de novo by overprinting the Tax gene. Intriguingly, several genes in the same genomic region have also originated de novo and encode proteins that regulate the functions of Tax. Such “gene nurseries” may be common in viral genomes. Finally, our results confirm that the genomic GC content is not the only determinant of codon usage in viruses and suggest that a constraint linked to translation must influence codon usage.

Evolution of New Functions De Novo and from Preexisting Genes

“…This process has been documented in prokaryotes (Delaye et al 2008) and in eukaryotes (Neme and Tautz 2013) but appears to be uncommon. In contrast, this mechanism appears to be widely used in many groups of viruses (Sabath et al 2012;Pavesi et al 2013).…”

Evolutionary Origins of a Bioactive Peptide Buried within Preproalbumin

“…This involves the use of a different frame, but the original frame may also be used so that effectively there become two genes that overlap. Overprinting has been observed in several species but is especially well documented in viruses (Pavesi et al, 2013). For most examples of de novo evolution, the focus is on the gene with little attention paid to the event or events that permit the protein to become a stable component of an organism's proteome.…”

Discovery and Characterization of Auxiliary Proteins Encoded by Type 3 Simian T-Cell Lymphotropic Viruses

“…Thus, all deltaretroviruses seem to utilize convergent evolutionary strategies that allow coding of auxiliary proteins. As is the case for HTLV-1 and HTLV-2, these genes likely originated by overprinting of other viral proteins (100).…”