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Experimental Test of Solitary Wave Theory in Viral Populations

by Dutta, Ranendra Nath

Abstract (Summary)
RNA viruses have a high mutation rate due to the absence of post replicative error correction machinery. This, coupled with high yield and a short replication interval leads to the generation of extensive genetic diversity that promotes rapid adaptation to novel environments. The fitness of a population determines the frequency of neutral, deleterious and beneficial mutations that arise during replication, with the latter increasing in frequency as viral fitness increases. This work shows that there is a direct correlation between fitness and log CBS with population size ranging over five orders of magnitude, and this correlation explains limits to fitness gains and drift in populations of very high fitness. Two theories of asexual evolution were tested. Solitary wave theory was shown to explain accurately the fitness changes of viral populations evolved under a variety of conditions. Furthermore, fit of experimental data to solitary wave allowed the determination of biologically-meaningful, important parameters relevant to the evolution of VSV strains, including number of sites under moderate selection, number of sites under positive selection with their average selective value, and diversity within the population. Clonal interference theory is a good predictor of DNA-based microbes, but is proved unsatisfactory as a descriptor of RNA virus evolution because of their high mutation rates and assumptions of the model that do not apply to these pathogens (e.g. populations are at mutation-selection balance). In particular, the results of determining the order of mutation accumulation clearly showed the ability of RNA viruses to generate secondary beneficial mutations before the primary beneficial mutation is fixed, or even dominant. This result clearly demonstrates that clonal interference theory is a poor descriptor of the evolutionary behavior of RNA viruses.
Bibliographical Information:

Advisor:

School:University of Toledo Health Science Campus

School Location:USA - Ohio

Source Type:Master's Thesis

Keywords:rna viruses clonal interference molecular evolution genetics vesicular stomatitis virus beneficial mutation

ISBN:

Date of Publication:01/01/2008

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