Extended Data Fig. 5: Mechanisms underlying coding mutations’ fitness effects.
From: Synonymous mutations in representative yeast genes are mostly strongly non-neutral
a–b, Box plots showing similar absolute fractional changes in the mRNA level induced by nonsynonymous (a) or synonymous (b) mutations within and outside TF-binding sites. The lower and upper edges of a box represent the first (qu1) and third (qu3) quartiles, respectively, the horizontal line inside the box indicates the median (md), the whiskers extend to the most extreme values inside inner fences, md ± 1.5(qu3-qu1), and the dots show outliers. P-values are from two-tailed Wilcoxon rank-sum test (n = 1191, 4736, 367, and 1411, respectively, for the four bars from left to right). c–d. Positive correlation between rCAI and rescaled fitness among nonsynonymous (c) and synonymous (d) mutants, respectively. e, Fraction of synonymous mutations lowering CAI increases with the expression level of the gene. f, Fraction of synonymous mutations lowering the expression level increases with the expression level of the gene. g, Fraction of nonsynonymous mutations lowering CAI increases with the expression level of the gene. h, Fraction of nonsynonymous mutations lowering the expression level increases with the expression level of the gene. i, Mean rescaled fitness of synonymous mutants declines with the expression level of the gene. j, Mean rescaled fitness of nonsynonymous mutants declines with the expression level of the gene. Because deleting a more highly expressed gene tends to cause a greater fitness reduction60, the finding in panel j means that the mean fitness reduction caused by a nonsynonymous mutation should rise with the expression level of the gene. In e-j, each dot represents a gene. k–l, positive correlation between the relative mRNA folding strength (rMFS) of a nonsynonymous (k) or synonymous (l) mutant and its rescaled fitness when rMFS is below 1. The rMFS of a mutant is its mRNA folding strength (i.e., the absolute value of its minimal folding energy) divided by that of the wild-type. In each panel, the correlation is separately computed for mutants with rMFS < 1 and those with rMFS > 1. In c-l, rank correlations (ρ) and associated P-values are shown
