FIGURE 2. Evolution of specificity-determining Ala¹⁸⁹ and Glu²²⁶ in human cathepsin G.

Codon sequence is shown below the corresponding residue. Mammalian consensus and predicted ancestral specificity determining Ser¹⁸⁹ (TCT) and Ala²²⁶ (GCA) sequence differ from human at both amino acids and at two nucleotides. Nucleotides and amino acids differing from predicted ancestral sequence are indicated in boldface and italics. Nucleotide changes in dog, cat, giant panda, cattle 2, rat, and mouse codons are synonymous. The likely evolutionary path (based on stepwise accumulation of missense mutations, as indicated) predicts that Ala¹⁸⁹ and Glu²²⁶ mutations in humans arose up to 7 million years ago (Mya) and between 31 and 43 Mya, respectively.