Abstract
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.
Highlights
Cells from several of the hematopoietic cell lineages store large amounts of proteases within cytoplasmic granules [1]
Serine proteases belonging to this family have in mammals been identified in neutrophils, cytotoxic T cells and natural killer (NK) cells, as well as in mast cells and basophils but not in B cells or dendritic cells and only at relatively low levels in eosinophils
In almost all mammals studied except rodents, the chymase locus contains only one mast cell expressed chymase gene, which is positioned at one end of the locus, adjacent to the region of non-protease bordering genes (Figure 1)
Summary
Cells from several of the hematopoietic cell lineages store large amounts of proteases within cytoplasmic granules [1]. In almost all mammals studied except rodents, the chymase locus contains only one mast cell expressed chymase gene, which is positioned at one end of the locus, adjacent to the region of non-protease bordering genes (Figure 1). In the two amphibians analyzed, the American clawed frog and the Western clawed frog, we can find both the classical chymase locus and the related locus found in reptiles and birds (Figure 2) In these two amphibians, these two loci are located within the same chromosomal region relatively close to each other, indicating that they may have been part of the same original locus (Figure 2). None of the genes that cluster with the classical chymase locus genes in mammals, reptiles and amphibians were found in any of the fish species we have analyzed [19]
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