AN ADAPTIVE WALK BY HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 THROUGH A FLUCTUATING FITNESS LANDSCAPE

The mutational landscape model of adaptive sequence evolution has been used to explain an unexpected strong positive linear relationship between marginal fitness and mean site-specific amino acid frequency in the functionally important HIV-1 gp120 V3 protein region. The model predicts a positive linear relationship between the probability that a particular beneficial allele, among several, is the next to spread to fixation during an adaptive walk, its transition probability, and the allele's selection coefficient. Here, stochastic simulation is used to confirm the intuition that the linear relationship between transition probabilities and selection coefficients, predicted by the model, should, under fluctuating selection, produce a linear relationship between allele frequency, averaged across populations, and fitness. In addition, these relationships hold for the effective population size and mutation rate of HIV-1 and for the moderately strong selection observed for V3. A survey of the strength of mutation for diverse organisms suggests that these relationships may be widely applicable.