The relationship between enzyme connectivity in the yeast metabolic network and evolutionary constraint quantified by the Ka/Ks ratio. Spearman's rank correlation r = -0.20, P = 1.1 × 10-4; Pearson's correlation r = -0.18, P = 7 × 10-4. The connectivity of a metabolic enzyme is equal to the total number of other network enzymes producing or consuming the enzyme's reactants and products. Ka is the fraction of amino acid replacement substitutions per amino acid replacement site on DNA; Ks is the fraction of silent substitutions per silent site on DNA. The inset shows the histogram of binned enzyme connectivity versus median evolutionary constraint Ka/Ks (using the same data as in the main figure). The standard errors in each bin are also shown.