Evolution of Mammalian Chitinase(-Like) Members of Family 18 Glycosyl Hydrolases

Abstract

Family 18 of glycosyl hydrolases encompasses chitinases and so-called chi-lectins lacking enzymatic activity due to amino acid substitutions in their active site. Both types of proteins widely occur in mammals although these organisms lack endogenous chitin. Their physiological function(s) as well as evolutionary relationships are still largely enigmatic. An overview of all family members is presented and their relationships are described. Molecular phylogenetic analyses suggest that both active chitinases (chitotriosidase and AMCase) result from an early gene duplication event. Further duplication events, followed by mutations leading to loss of chitinase activity, allowed evolution of the chi-lectins. The homologous genes encoding chitinase(-like) proteins are clustered in two distinct loci that display a high degree of synteny among mammals. Despite the shared chromosomal location and high homology, individual genes have evolved independently. Orthologs are more closely related than paralogues, and calculated substitution rate ratios indicate that protein-coding sequences underwent purifying selection. Substantial gene specialization has occurred in time, allowing for tissue-specific expression of pH optimized chitinases and chilectins. Finally, several family 18 chitinase-like proteins are present only in certain lineages of mammals, exemplifying recent evolutionary events in the chitinase protein family.

Accumulation of Ym1 and formation of intracellular crystalline bodies in alveolar macrophages lacking heparanase

“…Ym1 belongs to a group of chitinase-like proteins, including Ym2 and BRP-39 in mice, and YKL-40 in humans (Bussink et al, 2007). Increased expression of these proteins has been associated with inflammatory diseases, in particular with allergic asthma (reviewed in (Lee et al, 2008;Shuhui et al, 2009).…”

Bacterial chitinases and chitin-binding proteins as virulence factors

“…These families attain the triosephosphate isomerase (TIM) barrel and bilobal secondary structures, respectively, and differ in their reaction mechanisms, with family 18 enzymes operating with overall retention of the anomeric configuration at the cleavage point, and family 19 operating by inversion of the anomeric configuration (Henrissat, 1999). The two families most likely evolved from different ancestors (Bussink et al, 2007). Family 18 chitinases occur in viruses, bacteria, archaea and eukaryotes (Fig.…”

Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide-binding properties

“…Despite a relatively high sequence identity and predicted structural similarity to the family 18 chitinases such as chitotriosidase and AMCase, chitinase-like proteins lack glycosyl hydrolase activity [30]. The loss of enzymatic activity is attributed to the substitution of the catalytic residues of the DxxDxDxE motif, which characterizes the active site of family 18 chitinases [13,[31][32][33][34].…”