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Review article - Peer-reviewed, 2021

The Evolutionary History of the Chymase Locus -a Locus Encoding Several of the Major Hematopoietic Serine Proteases

Akula, Srinivas; Fu, Zhirong; Wernersson, Sara; Hellman, Lars


Several hematopoietic cells of the immune system store large amounts of proteases in cytoplasmic granules. The absolute majority of these proteases belong to the large family of chymotrypsin-related serine proteases. The chymase locus is one of four loci encoding these granule-associated serine proteases in mammals. The chymase locus encodes only four genes in primates, (1) the gene for a mast-cell-specific chymotryptic enzyme, the chymase; (2) a T-cell-expressed asp-ase, granzyme B; (3) a neutrophil-expressed chymotryptic enzyme, cathepsin G; and (4) a T-cell-expressed chymotryptic enzyme named granzyme H. Interestingly, this locus has experienced a number of quite dramatic expansions during mammalian evolution. This is illustrated by the very large number of functional protease genes found in the chymase locus of mice (15 genes) and rats (18 genes). A separate expansion has also occurred in ruminants, where we find a new class of protease genes, the duodenases, which are expressed in the intestinal region. In contrast, the opossum has only two functional genes in this locus, the mast cell (MC) chymase and granzyme B. This low number of genes may be the result of an inversion, which may have hindered unequal crossing over, a mechanism which may have been a major factor in the expansion within the rodent lineage. The chymase locus can be traced back to early tetrapods as genes that cluster with the mammalian genes in phylogenetic trees can be found in frogs, alligators and turtles, but appear to have been lost in birds. We here present the collected data concerning the evolution of this rapidly evolving locus, and how these changes in gene numbers and specificities may have affected the immune functions in the various tetrapod species.


mast cell; tryptase; chymase; serine protease; evolution; granzyme

Published in

International Journal of Molecular Sciences
2021, volume: 22, number: 20, article number: 10975
Publisher: MDPI

Authors' information

Uppsala University
Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry (AFB)
Fu, Zhirong
Uppsala University
Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry (AFB)
Hellman, Lars
Uppsala University

UKÄ Subject classification

Evolutionary Biology

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