New paralogues and revised time line in the expansion of the vertebrate GH18 family

J Mol Evol. 2013 Apr;76(4):240-60. doi: 10.1007/s00239-013-9553-4. Epub 2013 Apr 5.


Chitinase enzymes hydrolyse the polysaccharide chitin, an abundant architectural component in invertebrates and fungi. Most mammals encode at least two endochitinases (CHIT1 and CHIA/AMCase), as well as several homologues encoding catalytically inactive chitinase-like proteins or chilectins (all GH18 family proteins). It is becoming increasingly apparent that chitinases and chilectins play an important role in inflammation and their over-expression is correlated with numerous pathological conditions. We have conducted a detailed phylogenomic study of this gene family in order to understand its evolutionary history and the selection forces at work. The family has undergone extensive expansion, initiating with a duplication event at the root of the vertebrate tree generating the ancestors of CHIT1 and CHIA. Our analyses indicate that two further duplications of ancestral CHIA predate the divergence of bony fishes, one leading to a newly identified paralogous group (we have termed CHIO). In fish these sequences fall into two clades bearing the hallmarks of the teleost-specific genome duplication (referred to as 3R). In tetrapods, additional duplications predate and postdate the amphibian/mammalian split and relics of some exist as pseudogenes in the human genome. Expansion and selection of chilectins is pronounced in mammals and CHI3L1 (with a proposed function in immunity) is found in most mammals but not other vertebrates, while CHI3L2 is also evident in reptiles. Notably oviductin (OVGP1) became basic and gained a glycosylated tail with its evolving role in the mammalian reproductive system. In each case, retention of the sugar-binding barrel structure has constrained positive selection to limited sites.

MeSH terms

  • Adipokines / genetics
  • Amphibians / genetics
  • Animals
  • Chitinase-3-Like Protein 1
  • Chitinases / genetics*
  • Data Mining
  • Evolution, Molecular*
  • Fishes / genetics
  • Gene Duplication
  • Genome, Human
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Glycosylation
  • Hexosaminidases / genetics
  • Humans
  • Lectins / genetics
  • Mammals / genetics
  • Multigene Family
  • Phylogeny*
  • Pseudogenes
  • Selection, Genetic
  • Serine Endopeptidases / genetics
  • Time Factors
  • Vertebrates / genetics*


  • Adipokines
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Glycoproteins
  • Lectins
  • OVGP1 protein, Bos taurus
  • Hexosaminidases
  • chitotriosidase
  • Chitinases
  • Serine Endopeptidases
  • oviductin