RNA Bacteriophage Φ6

Colorized electron microscope image of herpesviruses (yellow and green spheres) coinfecting a single cell. During coinfection, sexual reproduction can produce viral progeny that contain a mixture of genes found in the coinfecting parents.

Evolution of Thermotolerance and Life-History Trade-Offs

We are using phage Φ6 as a model to study how segmented RNA viruses evolve increased stability (survival) under various environmental stressors (McBride et al. 2008, BMC Evol Biol 8:231). Challenges such as elevated heat, increased salinity and lowered acidity can cause virus particles to quickly degrade, and to lose their ability to subsequently infect host cells. Ongoing projects merge experimental evolution and structural biology, to examine how changes in virus proteins such as lytic enzymes explain increased virion stability in the face of heat shock (Dessau et al. 2012, PLoS Genetics). This improved protein-stability may sometimes cause ‘life-history’ trade-offs, where increased virus survival evolves at the expense of reduced viral reproduction. We are studying whether compensatory mutations can alleviate trade-offs, and whether differences in genetic architecture among ancestor viruses affect the evolvability of their descendant lineages (Ogbunugafor et al. 2009, CSH Symp Quant Biol 74:109-118).

Evolution of Genetic Robustness and Evolvability

We use RNA phage Φ6 as a model to examine the evolution of mutational robustness: phenotypic constancy in the face of underlying mutational change. Our work showed that selection to maintain robustness was relaxed under virus co-infection, because complementation between virus genotypes was a ‘built-in’ mechanism that buffered mutational effects (Montville et al. 2005, PLoS Biology 3:1939). Additional results showed that lineages founded by robust viruses can adapt faster than those initiated by brittle (non-robust) viruses, demonstrating a positive link between robustness and evolvability (McBride et al. 2008, BMC Evol Biol 8:231). Our ongoing studies continue to examine the relationship between robustness and evolvability, and generalized effects of robustness in the evolution of infectious diseases (Ogbunugafor et al. 2010, Chaos 20:026108).

Evolution of sex and its consequences

We use the RNA bacteriophage Φ6 as a model to study the costs and benefits of genetic exchange (sex). When multiple viruses co-infect the same host cell, sex produces hybrid progeny containing a mixture of genetic information from the co-infecting parents.

Sex may benefit viruses by promoting genetic variation, which might allow sexual populations to evolve faster than asexual ones. In contrast, sex requires co-infection and may exert a cost because it increases competition between viruses for limited intracellular resources.

One experiment allowed replicate populations of Φ6 to evolve in the presence and absence of sex for hundreds of viral generations (Turner and Chao 1998, Genetics 150:523-532). Unexpectedly, sex was costly because sexually-evolved viruses became attenuated (weakened) in their ability to infect the host alone. This indicates that the cost of intra-host competition can outweigh any of the potential benefits associated with sex.

Ongoing projects examine whether sex is advantageous in purging epistatic (interacting) mutations from the virus genome, whether sex is costly in terms of breaking apart co-adapted loci, and how reproductive system (sexuality versus asexuality) influences the rate of molecular evolution and prevalence for epistasis to evolve.

Game theory and virus interactionsExpected fitness values for a game in which opponents utilize conflicting strategies of cooperation and defection. Entries in the payoff matrix represent the fitness to an individual adopting the strategy on the left, if the opponent adopts the strategy above. Defectors gain a fitness advantage (1 + s2) that allows them to invade a population of cooperators. If the cost of defection is too strong, (1 - c) < (1 - s1), cooperators may also invade and the two strategies are driven to a stable polymorphism. Prisoner's dilemma occurs if it always pays to be selfish, (1 - c) > (1 - s1); defection sweeps through the population despite the greater fitness payoff had all individuals cooperated.

“Name me somebody that is not a parasite, and I’ll go out and say a prayer for him”
– Bob Dylan (Visions of Johanna, 1966)

The manufacture of diffusible, and hence shared, intracellular products during virus co-infection allows for the conflicting strategies of cooperation and defection (selfishness). Whereas a viral genotype that synthesizes larger quantities of product is effectively a cooperator, a genotype that synthesizes less but specializes in sequestering a larger share of the products is a defector.

We use phage Φ6 to study the evolution of viral conflicts. One study showed that viruses cultured under high levels of co-infection evolve selfish strategies, but their fixation in the population causes mean fitness to decline (Turner and Chao 1999, Nature 398:441-443). These data conform to the prisoner’s dilemma of game theory, where selfishness evolves despite the greater fitness payoff if all players cooperate.

Ongoing projects examine the generality of the prisoner’s dilemma result in Φ6; for instance, evolved cooperator viruses can re-invade populations of defectors, allowing the two strategies to coexist in a stable polymorphism (Turner and Chao 2003, American Naturalist 161:497-505). Current research examines the molecular mechanism(s) that may afford selfish genotypes an advantage during intra-host competition. We are also examining whether viruses evolve specific mechanisms to exclude large numbers of viruses from co-infecting the same cell, in order to reduce intracellular competition (Turner et al. 1999, Journal of Virology 73:2420-2424).

Evolutionary ecology of host shifts

A virus’s ecological niche is governed in part by its host range, the hosts in which a virus can produce viable progeny. Viruses may expand their host range through mutations that facilitate entry into new host environments. Although host shifts allow a virus (or any other parasite) to expand its ecological niche, traits governing the infection of multiple host types can decrease fitness in the original or alternate host environments. We use phage Φ6 and Pseudomonas bacteria as a model to test basic questions relating to evolutionary ecology of host shifts. Ongoing projects include measuring the mutation spectrum associated with expanded host range, growth tradeoffs for host range mutants across host environments, and strength of selection resulting from simultaneous adaptation of viruses to multiple habitats.