When two viruses infect a single host cell, they interact in ways that influence their evolution and pathogenesis. I will investigate two such interactions: 1) complementation, the masking of an allele carried by one virus by the homologous allele carried by the other virus, and 2) selfishness, the exploitation of a shared resource by one allele at a cost to the homologous allele. These interactions allow the persistence of mutations that reduce fitness (i.e. deleterious and selfish mutations), and slow the fixation of beneficial mutations. Although complementation and selfishness have been observed to affect the evolution of drug resistance and virulence in particular cases, the general nature of these interactions and the frequency with which they arise in viruses has not been studied. I will conduct evolution experiments to examine the causes and fitness consequences of complementation and selfishness in the bacteriophage 96.
Specific Aim 1. Determine whether the physiological theory of dominance accurately predicts the effects of complementation in viruses. I will perform two sets of experiments to test this. The first will examine the relationship between dominance and selection coefficients of deleterious mutations to determine whether, as predicted by the physiological theory of dominance, they are negatively correlated. The second will examine this relationship for beneficial mutations accumulated in populations where viruses are haploid.
Specific Aim 2 : Determine whether the genetic basis of adaptation differs between haploid and diploid populations. I will examine this in two ways. First, I will determine whether adaptive mutations accumulated in diploid populations are more often selfish than those accumulated in haploid populations. Second, I will measure the dominance coefficients of beneficial mutations accumulated in populations where viruses are effectively diploid (i.e. host cells are typically infected by two viruses). I will then use data from this second experiment to test whether adaptive mutations accumulated in diploid populations are, as predicted by Haldane's Sieve, more dominant that mutations accumulated in haploid populations. Relevance: Interactions between viruses during dual infections may affect the virulence of infections and the evolution of drug resistance. As a result, understanding these interactions in bacteriophage may provide insights into the evolution and pathogenesis of viral pathogens of humans. ? ? ?

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F08-G (20))
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Portnoy, Matthew
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University of North Carolina Chapel Hill
Schools of Arts and Sciences
Chapel Hill
United States
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Joseph, S B; Kirkpatrick, M (2008) Effects of the [PSI+] prion on rates of adaptation in yeast. J Evol Biol 21:773-80