Abstract
Serine proteases are among the most abundant granule constituents of several hematopoietic cell lineages including mast cells, neutrophils, cytotoxic T cells and NK cells. These proteases are stored in their active form in the cytoplasmic granules and in mammals are encoded from four different chromosomal loci: the chymase locus, the met-ase locus, the T cell tryptase and the mast cell tryptase locus. In order to study their appearance during vertebrate evolution we have performed a bioinformatic analysis of related genes and gene loci from a large panel of metazoan animals from sea urchins to placental mammals for three of these loci: the chymase, met-ase and granzyme A/K loci. Genes related to mammalian granzymes A and K were the most well conserved and could be traced as far back to cartilaginous fish. Here, the granzyme A and K genes were found in essentially the same chromosomal location from sharks to humans. However in sharks, no genes clearly identifiable as members of the chymase or met-ase loci were found. A selection of these genes seemed to appear with bony fish, but sometimes in other loci. Genes related to mammalian met-ase locus genes were found in bony fish. Here, the most well conserved member was complement factor D. However, genes distantly related to the neutrophil proteases were also identified in this locus in several bony fish species, indicating that this locus is also old and appeared at the base of bony fish. In fish, a few of the chymase locus-related genes were found in a locus with bordering genes other than the mammalian chymase locus and some were found in the fish met-ase locus. This indicates that a convergent evolution rather than divergent evolution has resulted in chymase locus-related genes in bony fish.
Highlights
560 protease genes are present in primate genomes and around 150 of these encode proteases of the serine protease class
The Evolutionary History of Hematopoietic Serine Proteases trypsin/chymotrypsin related serine protease family making them one of the major protease families [1]. Serine proteases of this latter family are found at very high levels in the granules of cells of several hematopoietic cell lineages including mast cells, neutrophils, cytotoxic T cells and NK cells, where they can account for up to 35% of the total cellular protein [2]
Through a detailed analysis of the genes related to three of the four loci encoding the various hematopoietic serine proteases in mice and humans, we have been able to show that the first clearly identifiable members of this big class of proteases appeared with the cartilaginous fish
Summary
560 protease genes are present in primate genomes and around 150 of these encode proteases of the serine protease class. The Evolutionary History of Hematopoietic Serine Proteases trypsin/chymotrypsin related serine protease family making them one of the major protease families [1] Serine proteases of this latter family are found at very high levels in the granules of cells of several hematopoietic cell lineages including mast cells, neutrophils, cytotoxic T cells and NK cells, where they can account for up to 35% of the total cellular protein [2]. Members of this protease family take part in a large number of physiological processes including blood coagulation, clot resolution, complement activation, food digestion, fertilization, blood pressure regulation, tissue homeostasis, and immunity. Members of this gene family include thrombin, plasmin, tissue plasminogen activator (TPA), urokinase, coagulation factors VII, IX, X, XI, XII and protein C, complement components B, D, C2, C1r, C1s, factor I, the numerous tissue kallikreins, acrosin, leydin, testin, pancreatic trypsin, chymotrypsin, elastase, haptoglobin and all the different granule associated hematopoietic serine proteases that are the theme of this communication
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