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A highly unexpected strong correlation between fixation probability of nonsynonymous mutations and mutation rate
Authors:Wyckoff Gerald J  Malcom Christine M  Vallender Eric J  Lahn Bruce T
Institution:Howard Hughes Medical Institute, Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Abstract: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.
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