A highly unexpected strong correlation between fixation probability of nonsynonymous mutations and mutation rate

Under prevailing theories, the nonsynonymous-to-synonymous substitution ratio (i.e. K-a/K-s), which measures the fixation probability of nonsynonymous mutations, is correlated with the strength of selection. In this article, we report that K-a/K-s is also strongly correlated with the mutation rate as measured by K-s, and that this correlation appears to have a similar magnitude as the correlation between K-a/K-s and selective strength. This finding cannot be reconciled with current theories. It suggests that we should re-evaluate the current paradigms of coding-sequence evolution, and that the wide use of K-a/K-s as a measure of selective strength needs reassessment.