Diminishing returns of population size in the rate of RNA virus adaptation

Whenever an asexual viral population evolves by adapting to new environment al conditions, beneficial mutations, the ultimate cause of adaptation, are randomly produced and then fixed in the population. The larger the populati on size and the higher the mutation rate, the more beneficial mutations can be produced per unit time, With the usually high mutation rate of RNA viru ses and in a large enough population, several beneficial mutations could ar ise at the same time but in different genetic backgrounds, and if the virus is asexual, they will never be brought together through recombination, Thu s, the best of these genotypes must outcompete each other on their way to f ixation, This competition among beneficial mutations has the effect of slow ing the overall rate of adaptation. This phenomenon is known as clonal inte rference. Clonal interference predicts a speed limit for adaptation as the population size increases. In the present report, by varying the size of ev olving vesicular stomatitis virus populations, we found evidence clearly de monstrating this speed limit and thus indicating that clonal interference m ight be an important factor modulating the rate of adaptation to an in vitr o cell system. Several evolutionary and epidemiological implications of the clonal interference model applied to RNA viruses are discussed.