title: Phylogeny of antigen-processing enzymes: cathepsins of a cephalochordate, an agnathan and a bony fish.
abstract: Cathepsins are enzymes that have been cleaving peptide bonds of lysosomal proteins probably since lysosomes appeared in early eucaryotes. When the adaptive system emerged in gnathostomes, cathepsins were recruited to produce peptides for loading onto the major histocompatibility complex class II molecules and for degrading the class II-associated invariant chain just before the loading. The circumstances under which this recruitment took place are unclear because the knowledge about vertebrate cathepsins is limited largely to mammals. To shed light on the recruitment, 10 amphioxus, one lamprey and one cichlid fish cathepsin cDNA clone were characterized and analysed phylogenetically. Disregarding cathepsin O, whose phylogenetic position is uncertain, the analysis confirms the existence of two old lines of descent, the B and the L lineages of cathepsins, which diverged from each other early in the evolution of eucaryotes. The B lineage encompasses cathepsins B, C and Z (X). The L lineage splits off sublineages encompassing cathepsins F and W before the plant-animal separation and cathepsin H early in the evolution of the metazoa. The remaining cathepsins belonging to the L lineage diverged from one another during the evolution of vertebrates: S, K and L before the emergence of bony fishes, and the group of rodent placentally expressed cathepsins [J (P), M, Q, R, 3, 6, 7 and 8] as well as the testis/ova-expressed cathepsins (testins) probably after the divergence of rodents from primates. The part possibly played by the adaptive immune system in some of these divergences is discussed.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001483:Base Sequence; D002403:Cathepsins / Q000235:genetics*; D002816:Chordata, Nonvertebrate / Q000201:enzymology / Q000235:genetics*; D023681:Cichlids / Q000235:genetics*; D018076:DNA, Complementary; D007798:Lampreys / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment
chemical_list: D018076:DNA, Complementary; D002403:Cathepsins