Figure WN22.9. (A) The proportion of amino acid substitutions in a nonhuman species that would cause disease if present in humans (i.e., the fraction of compensated pathogenic deviations [CPDs]) plotted against amino acid divergence. (B) An example of a CPD. Mutations that replace Val by Glu at position 20 in human β-hemoglobin are pathogenic and yet are present in several other species, including horse. Those species always have His at position 69, whereas humans have Gly at this position. It is thought that both Glu-His and Val-Gly can interact to maintain the hemoglobin structure. (A, Redrawn from Fig. 3B of Kondrashov et al. 2002; B, redrawn from Fig. 5B of Kondrashov et al. 2002.)

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