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Epistatic interactions can lower the cost of resistance

Michael Travisano¹, Brendan J. M. Bohannan², and Richard E. Lenski^3
1Department of Biology and Biochemistry, University of Houston, Houston TX 77204
²Department of Biological Sciences, Stanford University, Palo Alto, CA 94305
³Center for Microbial Ecology, Michigan State University, East Lansing, MI 48824

Evolutionary interactions between a virus and its host are strongly affected by the cost of resistance. The evolution of viral virulence, the persistence of susceptible hosts, and the commonality of resistance can all be affected by changes in the cost of resistance. The Œcost_ is the reduction in competitive ability of a virus resistant host relative to a susceptible host in the absence of virus. Such a cost is expected to arise if there is a trade-off in competitive ability and resistance.

However, it is actually unclear what factors determine the cost of resistance. Determining fitness (competitive ability) is impossible for many organisms, even without the complication of viral resistance. To avoid these difficulties, we have been using a bacteria and phage model system (E. coli B and phages T4 and lvir). Bacteria and bacteriophage provide an ideal system to examine the costs of resistance: environmental conditions are easily controlled, virus and host genotypes can be readily obtained, and abundant information is available on the mechanisms of resistance.

We demonstrated that epistasis between genes that confer resistance to phages T4 and lvir can alter the cost of resistance. Epistasis tended to reduce the costs of multiple resistance in this system, although the savings depended upon the environment and specific resistance mutations. In glucose-minimal medium, T4 and lvir resistant double mutants tended to have slightly higher fitness than expected based on the separate effects of the T4- and lvir- resistant mutations. However, this effect was not significant based on a two-tailed test. In trehalose-minimal medium, the difference between the expected and observed were more pronounced: 8 of 10 double mutants had extreme fitness values in comparison with that expected. Even so, there was no average trend for the extreme fitness, 6 had higher observed fitness while 2 had lower fitness values. Thus there is frequent epistasis among T4- and lvir- resistant mutations for fitness in the trehalose environment, but the epistatic effects are highly variable.

Our results indicate that the cost of resistance depends on the specific phenotype as well as the environment in which the cost is measured. Whether there are significant epistatic interactions among resistance mutations for fitness depends on the environment. The sign and strength of the epistasis also depends on subtle differences among mutations within a given resistance class. Overall, there is a tendency for the cost of multiple resistances to be less than expected.

Abstract - Presented at the Virus Evolution Workshop
Ardmore, OK
October 21 - 24th, 1999

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Dr. Marilyn Roossinck
Plant Biology Division
The Noble Foundation
P.O. Box 2180
Ardmore, OK 73402

phone: 580 224-6630