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.
Wyckoff
Gerald J
GJ
Howard Hughes Medical Institute, Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Malcom
Christine M
CM
Vallender
Eric J
EJ
Lahn
Bruce T
BT
D000818:Animals; D005075:Biological Evolution; D018899:CpG Islands; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D011336:Probability