Viruses infecting a host cell can interact in ways that influence their evolution and pathogenesis. Bacteriophage provide unique opportunities for examining two of these interactions: complementation and selfishness. Complementation occurs when an allele carried by one virus masks the effects of an allele carried by another virus and selfishness occurs when an allele carried by one virus receives a fitness advantage while reducing the fitness of homologous alleles. These interactions can allow mutations that reduce populations mean fitness (deleterious and selfish alleles) to persist in populations and slow the fixation of beneficial alleles. We are proposing a series of experimental evolution studies examining the causes and fitness consequences of complementation and selfishness in the bacteriophage, Phi6. AIM 1: Determine whether the physiological theory of dominance accurately predicts the effects of complementation. In this aim we will examine whether the physiological theory of dominance can explain the relationship be selection and dominance coefficients associated with deleterious and beneficial mutations. The deleterious mutations generated examined in this aim will be generated by site-directed mutagenesis in three functional regions: an enzymatic gene, a structural gene, and regulatory regions. The use of site-directed mutagenesis allows us to explicitly test this model for mutations with different functional effects. In the second half of this aim we will test the physiological theory’s prediction that dominance and selection coefficients associated with beneficial mutations are positively correlated. AIM 2: Determine whether the genetic basis of adaptation differs between haploid and diploid populations. We will accomplish this by measuring the examining beneficial mutations accumulated in haploid (i.e. host cells are typically infected by one virus) are effectively diploid (i.e. host cells are typically infected by two viruses) populations. We will then test whether adaptive mutations accumulated in diploid populations are, as predicted by Haldane’s Sieve, more dominant that mutations accumulated in haploid populations. We will then examine whether adaptive mutations accumulated in diploid populations are more selfish than those accumulated in haploid populations.
|Effective start/end date||7/1/07 → 6/30/09|
- NIH National Institute of General Medical Sciences (NIGMS)
Nucleic Acid Regulatory Sequences