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 nem atode Haemonchus contortus was demonstrated. To assess potential functional diversity, multiple nematode CBL sequences were compared with known functi onal domains of cathepsin B. These domains included the occluding loop, S2' and S2 subsites, and the pro region. Four groups of CBLs were defined base d on variable characteristics in the occluding loop region, which incorpora tes a portion of the S2' subsite. Further diversity was observed in amino a cids expected to contribute to the S2 subsite. In addition, short signature sequences near the cysteinyl active site region characterized known CBLs o f parasites from the orders Strongylida and Rhabditida. The criteria establ ished were used to identify two predicted CBLs from parasitic (Ascaris suum ) and free-living (Caenorhabditis elegans) nematodes as potential orthologu es, and provided a basis to evaluate orthologue status of other CBLs. Varia bility 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 dif ferences in CBLs among species and groups of nematodes. Nutrient digestion is one potential factor promoting CBL diversification in these organisms. ( C) 1999 Elsevier Science B.V. All rights reserved.