Evolution of cysteine proteinases in eukaryotes.

Phylogenetic analyses of the major family of cysteine proteinases of eukaryotes revealed that this family has been characterized by numerous gene duplications, several of which occurred very early in eukaryote evolutionary history. For example, certain cysteine proteinases from plants and animals are homologous to each of the two cysteine proteinases of the protist Dictyostelium discoideum, indicating that these genes duplicated prior to the divergence of Dictyostelium, plants, and animals. All members of this gene family from metazoan parasites clustered in a well-defined subfamily with mammalian cathepsin B, whereas all those from protist parasites clustered outside this subfamily. Five members of this subfamily from Haemonchus contortus (a nematode parasite of sheep and other ruminants) evolved by gene duplications which were estimated to have occurred within the past 200 My. The proteins encoded by these five genes show a surprising number of residue charge differences from each other, particularly in helical regions in or near the substrate-binding cleft. Statistical analysis of DNA sequences showed that nonsynonymous nucleotide differences that cause amino acid residue charge changes have occurred in these regions at a greater rate than expected under random substitution, suggesting that these genes have diversified as a result of positive natural selection favoring such changes.