Defined characteristics of cathepsin B-like proteins from nematodes: inferred functional diversity and phylogenetic relationships.

Numerous cathepsin B-like protein sequences (CBLs) have been reported from nematodes. However, the relationships among these proteins remain unclear. Here, expression of several CBL transcripts in the gut of the parasitic nematode Haemonchus contortus was demonstrated. To assess potential functional diversity, multiple nematode CBL sequences were compared with known functional domains of cathepsin B. These domains included the occluding loop, S2' and S2 subsites, and the pro region. Four groups of CBLs were defined based on variable characteristics in the occluding loop region, which incorporates a portion of the S2' subsite. Further diversity was observed in amino acids expected to contribute to the S2 subsite. In addition, short signature sequences near the cysteinyl active site region characterized known CBLs of parasites from the orders Strongylida and Rhabditida. The criteria established were used to identify two predicted CBLs from parasitic (Ascaris suum) and free-living (Caenorhabditis elegans) nematodes as potential orthologues, and provided a basis to evaluate orthologue status of other CBLs. Variability in the domains analyzed suggests substantial functional diversity in enzymatic properties of nematode CBLs. Results suggest that the selective amplification and evolution of distinct CBL lineages has contributed to differences in CBLs among species and groups of nematodes. Nutrient digestion is one potential factor promoting CBL diversification in these organisms.