Transmission bottlenecks and the evolution of fitness in rapidly evolving RNA viruses.

We explored the evolutionary importance of two factors in the adaptation of RNA viruses to their cellular hosts, size of viral inoculum used to initiate a new infection, and mode of transmission (horizontal versus vertical). Transmission bottlenecks should occur in natural populations of viruses and their profound effects on viral adaptation have been previously documented. However, the role of transmission mode has not received the same attention. Here we used a factorial experimental design to test the combined effects of inoculum (bottleneck) size and mode of transmission in evolution of vesicular stomatitis virus (VSV) in tissue culture, and compared our results to the predictions of a recent theoretical model. Our data were in accord with basic genetic principles concerning the balance between mutation, selection and genetic drift. In particular, attenuation of vertically transmitted viruses was a consequence of the random accumulation of deleterious mutations, whereas horizontally transmitted viruses experiencing similar bottlenecks did not suffer the same fitness losses because effective bottleneck size was actually determined by the number of host individuals. In addition, high levels of viral fitness in horizontally transmitted populations were explained by competition among viral variants.