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Why do RNA viruses recombine?

Nature Reviews Microbiology volume 9, pages 617–626 (2011)Cite this article

Subjects

Key Points

  • RNA viruses are able to undergo two forms of recombination: RNA recombination, which (in principle) can occur in any type of RNA virus, and reassortment, which is restricted to those viruses with segmented genomes.

  • Rates of RNA recombination vary markedly among RNA viruses. Some viruses, particularly those with negative-sense single-stranded genomes, exhibit such low rates of recombination that they are effectively clonal. By contrast, some positive-sense single-stranded RNA viruses and some retroviruses such as HIV exhibit high rates of recombination that can exceed the rates of mutation when measured per nucleotide.

  • Although recombination is often argued to represent a form of sexual reproduction, there is little evidence that recombination in RNA viruses evolved as a way of creating advantageous genotypes or removing deleterious mutations. In particular, there is no association between recombination frequency and the burden of a deleterious mutation. Similarly, there is little evidence that recombination could have been selected as a form of genetic repair.

  • The strongest association for rates of recombination in RNA viruses is with genome structure. Hence, negative-sense single-stranded RNA viruses may recombine at low rates because of the restrictive association of genomic RNA in a ribonucleoprotein complex, as well as a lack of substrates for template switching, whereas some retroviruses recombine rapidly because their virions contain two genome copies and template switching between these copies is an inevitable part of the viral replication cycle.

  • We therefore hypothesize that recombination in RNA viruses is a mechanistic by-product of the processivity of the viral polymerase that is used in replication, and that it varies with genome structure.

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.

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Figure 1: Generation of recombinant and reassortant RNA viruses.
Figure 2: Potential consequences of a disassociation event during viral transcription.
Figure 3: Evolutionary consequences of recombination.

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Acknowledgements

E.C.H. is supported in part by US National Institutes of Health grant R01GM080533.

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Authors and Affiliations

  1. Department of Biology, Center for Infectious Disease Dynamics, Mueller Laboratory, The Pennsylvania State University, University Park, 16802, Pennsylvania, USA

    Etienne Simon-Loriere & Edward C. Holmes

  2. Fogarty International Center, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Edward C. Holmes

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  1. Etienne Simon-Loriere
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Correspondence to Edward C. Holmes.

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Glossary

Genomic segment

An independently replicating RNA molecule. RNA viruses can possess either a single segment (such that they are unsegmented) or multiple segments. Those with multiple segments may experience reassortment.

Defective interfering particles

Defective viruses (usually possessing long genome deletions) that compete, and hence interfere, with fully functional viruses for cellular resources.

Virions

The final mature virus particles containing the RNA genome and the full set of proteins.

Processivity

A measure of the average number of nucleotides added by a polymerase enzyme per association–disassociation with the template during replication.

Packaging

The process by which the nucleic acid genome and other essential virion components are inserted in the structural core or shell of a virus particle.

Complementation

The process by which a defective virus can parasitize a fully functional virus that is infecting the same cell; the defective virus 'steals' the proteins of the functional virus to restore its own fitness.

Multiplicity of infection

(MOI). The ratio of viruses to the number of cells that are infected.

Breakpoint

The site in the genome sequence at which a recombination event has occurred. Phylogenetic trees are incongruent on either side of the breakpoint.

Linkage disequilibrium

(LD). The nonrandom association between alleles at two or more loci, being indicative of a lack of recombination. Recombination reduces LD.

Clonal interference

The process by which beneficial mutations compete, and hence interfere, with each other as they proceed toward fixation.

Epistasis

An interaction between mutations such that their combined effect on fitness is different to that expected from their stand-alone effects. Depending on the nature of the deviation, epistasis can be either antagonistic (positive) or synergistic (negative).

Genetic redundancy

The situation in which a specific phenotype is determined by more than one gene, such as members of multigene families.

Robustness

The constancy of a phenotype in the face of pressure from a deleterious mutation.

Provirus

The DNA form of a retroviral genome that is integrated into the genetic material of a host cell.

Genome dimerization

A non-covalent process by which retroviruses carry two RNA genomes in the virion.

Sequence space

All possible mutational combinations that are present in DNA or amino acid sequence data.

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Simon-Loriere, E., Holmes, E. Why do RNA viruses recombine?. Nat Rev Microbiol 9, 617–626 (2011). https://doi.org/10.1038/nrmicro2614

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