RNA Virus Evolution via a Fitness-Space Model

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THE RELATION OF RECOMBINATION TO MUTATIONAL ADVANCE.

J. Müller (1964)

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Smoothness within ruggedness: the role of neutrality in adaptation.

M Huynen, P. Stadler, W Fontana (1996)

RNA secondary structure folding algorithms predict the existence of connected networks of RNA sequences with identical structure. On such networks, evolving populations split into subpopulations, which diffuse independently in sequence space. This demands a distinction between two mutation thresholds: one at which genotypic information is lost and one at which phenotypic information is lost. In between, diffusion enables the search of vast areas in genotype space while still preserving the dominant phenotype. By this dynamic the success of phenotypic adaptation becomes much less sensitive to the initial conditions in genotype space.

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Exponential increases of RNA virus fitness during large population transmissions.

I S Novella, Greg J. Holland, Isabel S. Novella … (1995)

The great adaptability shown by RNA viruses is a consequence of their high mutation rates. Here we investigate the kinetics of virus fitness gains during repeated transfers of large virus populations in cell culture. Results always show that fitness increases exponentially. Low fitness clones exhibit regular increases observed as biphasic periods of exponential evolutionary improvement, while neutral clones show monophasic kinetics. These results are significant for RNA virus epidemiology, optimal handling of attenuated live virus vaccines, and routine laboratory procedures.