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. Ka/Ks), which measures the fixation probability of nonsynonymous mutations, is correlated with the strength of selection. In this article, we report that Ka/Ks is also strongly correlated with the mutation rate as measured by Ks, and that this correlation appears to have a similar magnitude as the correlation between Ka/Ks 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 Ka/Ks as a measure of selective strength needs reassessment.