The regulatory genome constrains protein sequence evolution: implications for the search for disease-associated genes.

Highly significant results on the effect of expression variance in each tissue on nonsynonymous substitution rate and evolutionary rate are obtained with human-mouse divergence (Spearman’s ρ ranges from −0.46 to −0.18, p < 2.20 × 10 −126 for dN and expression variance, and Spearman’s ρ ranges from −0.42 to −0.15, p < 5.20 × 10 −90 for dN/dS and expression variance).

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