Why do RNA viruses recombine?

Abstract

Recombination occurs in many RNA viruses and can be of major evolutionary significance. However, rates of recombination vary dramatically among RNA viruses, which can range from clonal to highly recombinogenic. Here, we review the factors that might explain this variation in recombination frequency and show that there is little evidence that recombination is favoured by natural selection to create advantageous genotypes or purge deleterious mutations, as predicted if recombination functions as a form of sexual reproduction. Rather, recombination rates seemingly reflect larger-scale patterns of viral genome organization, such that recombination may be a mechanistic by-product of the evolutionary pressures acting on other aspects of virus biology.

Figure 1. Generation of recombinant and reassortant RNA viruses.

a | Co-infection of a cell by genetically distinct viral strains can lead to the generation of recombinant viruses. This process can occur in both non-segmented viruses (as shown here) or within a segment of a segmented virus. b | Co-infection of a cell by genetically distinct strains of a retrovirus can lead to the generation of 'heterozygous' virus particles, after which a template-switching event can lead to a recombinant provirus. c | Co-infection of a cell by genetically distinct strains of a segmented virus can generate different combinations of reassortant progeny.

Figure 2. Potential consequences of a disassociation event during viral transcription.

Following disassociation of the viral polymerase and the nascent nucleic acid from the template, the polymerase has to find a template or the transcription process will abort. This re-association event can take place on the same template (red), at the same genomic position or at a different position. Alternatively, the polymerase can associate with a homologous template (orange), again either at the same genomic position or at a different position. Finally, re-association can take place on a non-homologous template, such as a cellular RNA (blue). Of all these possible RNA recombination events, those occurring at the same position on a homologous template are the most likely to generate functional progeny.

Figure 3. Evolutionary consequences of recombination.

Depending on the acceptor and donor genotypes, and the position of the template switch, recombination can have several positive effects on the genome. Yellow circles indicate wild-type loci. a | Recombination can create advantageous combinations of mutations (blue circles) that increase the rate of adaptive evolution compared with mutation alone, or it can disassociate advantageous and deleterious mutations, allowing the former to spread. b | Recombination can remove deleterious mutations (red circles) and restore the wild-type (fit) genotype, which can lead to a selective advantage for recombination if deleterious mutations occur frequently enough and interact synergistically. c | Recombination can also generate a functional genome from damaged parental molecules. Genetic damage, such as strand breaks or oxidative base modifications, are represented by red lightning symbols.