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Rapid Lineage-specific Diversification Of The Mast Cell Chymase Locus During Mammalian Evolution

Maike Gallwitz, L. Hellman
Published 2006 · Biology, Medicine

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Serine proteases constitute the major protein granule content of cells of several hematopoietic cell lineages. A subgroup of these proteases, including the mast cell chymases, neutrophil cathepsin G, and T cell granzymes B to F and N, are in all investigated mammals encoded in one locus, the chymase locus. It is interesting to note that this locus has diversified greatly during the last 95 Myr of mammalian evolution. This divergence is exemplified by the presence of Mcpt8-related genes and multiple β-chymases in the mouse and rat, which lack direct counterparts in primates and in seven functional granzyme genes in the mouse where the human locus has only two. To study the expansion of the locus during rodent evolution and to better understand the evolutionary origin of β-chymases and the Mcpt8-family, we have performed a detailed analysis of the chymase locus of four mammalian species, i.e., human, dog, mouse, and rat. As a result, we report here a second chymase-like gene in dog, Cma2, which clusters with β-chymases in phylogenetic analyses. This finding supports a duplication of the common ancestor for α- and β-chymases before the major radiation of placental mammals, and a loss of the ancestral β-chymase gene sometime during primate evolution. Moreover, we show that in the rat, the Mcpt8-family diversified relatively recently together with sequences related to the β-chymase Mcpt2. Eight novel genes were identified in the duplication region, four of which are predicted to be functional. Duplications of rat granzyme B- and C-like sequences occurred seemingly independently within a similar time frame, but did not give rise to functional genes. Due to the duplications in rat and deletions in the carnivore/primate lineage, the rat chymase locus is approximately 15 and 9 times larger than its counterparts in dog and human, respectively. These findings illustrate the importance of gene duplications in conferring rapid changes in mammalian genomes.
This paper references
10.1007/s00251-004-0703-0
Genomic organization and evolutionary analysis of Ly49 genes encoding the rodent natural killer cell receptors: rapid evolution by repeated gene duplication
Li Hao (2004)
10.1093/MOLBEV/MSG083
Adaptive diversification of bitter taste receptor genes in Mammalian evolution.
Peng Shi (2003)
Characterization and mast cell origin of a chymotrypsin-like proteinase isolated from intestines of mice infected with Trichinella spiralis.
G. Newlands (1987)
10.1172/JCI9997
A novel vascular smooth muscle chymase is upregulated in hypertensive rats.
C. Guo (2001)
Constitutive and inducible mechanisms for synthesis and release of cytokines in immune cell lines.
R. A. Baumgartner (1996)
10.1126/SCIENCE.276.5319.1687
Multiple and ancient origins of the domestic dog.
C. Vilà (1997)
Origins of functional diversity in mammalian mast cell peptidases. The Batsheva de Rothschild international workshop on mast cell signalling and function in health and disease
GH Caughey (2005)
Cloning of the cDNA for the serine protease homolog CAP37/azurocidin, a microbicidal and chemotactic protein from human granulocytes.
J. G. Morgan (1991)
10.1016/S0014-5793(97)00752-7
Induction of chymase that forms angiotensin II in the monkey atherosclerotic aorta
S. Takai (1997)
10.1006/GENO.1993.1115
The human mast cell chymase gene (CMA1): mapping to the cathepsin G/granzyme gene cluster and lineage-restricted expression.
G. Caughey (1993)
10.1002/JCB.240320105
The versatility of proteolytic enzymes
H. Neurath (1986)
10.1126/SCIENCE.1073906
Genetic Evidence for an East Asian Origin of Domestic Dogs
P. Savolainen (2002)
10.1042/BJ3110675
Cloning of the cDNA encoding a novel rat mast-cell proteinase, rMCP-3, and its expression in comparison with other rat mast-cell proteinases.
H. Ide (1995)
10.1021/BI00396A020
Amino acid sequence of rat mast cell protease I (chymase).
H. Le Trong (1987)
A chymotrypsin-type serine protease in rat basophilic leukemia cells: evidence for its immunologic identity with atypical mast cell protease.
H. Kido (1986)
10.1146/ANNUREV.BI.50.070181.002025
Organization and expression of eucaryotic split genes coding for proteins.
R. Breathnach (1981)
10.1101/GR.1946304
A genomic analysis of rat proteases and protease inhibitors.
X. S. Puente (2004)
10.1021/BI00427A054
Amino acid sequence of a mouse mucosal mast cell protease.
H. L. Trong (1989)
10.1074/jbc.M301512200
Extended Substrate Specificity of Rat Mast Cell Protease 5, a Rodent α-Chymase with Elastase-like Primary Specificity*
U. Karlson (2003)
10.1074/jbc.M308209200
Mouse Chromosome 17A3.3 Contains 13 Genes That Encode Functional Tryptic-like Serine Proteases with Distinct Tissue and Cell Expression Patterns*
G. W. Wong (2004)
10.1042/BST0330331
A genomic view of the complexity of mammalian proteolytic systems.
X. S. Puente (2005)
10.1074/JBC.274.28.19670
Human Tryptases α and β/II Are Functionally Distinct Due, in Part, to a Single Amino Acid Difference in One of the Surface Loops That Forms the Substrate-binding Cleft*
C. Huang (1999)
10.1016/S0952-7915(03)00099-2
The orphan granzymes of humans and mice.
W. Grossman (2003)
10.1002/1521-4141(200009)30:9<2660::AID-IMMU2660>3.0.CO;2-I
MMCP‐8, the first lineage‐specific differentiation marker for mouse basophils. Elevated numbers of potent IL‐4‐producing and MMCP‐8‐positive cells in spleens of malaria‐infected mice
M. Poorafshar (2000)
Cutting Edge – Cleavage Specificity and Biochemical Characterization of Mast Cell Serine Proteases
U. Karlson (2003)
10.1016/S0097-8485(96)80013-1
Censor - a Program for Identification and Elimination of Repetitive Elements From DNA Sequences
J. Jurka (1996)
PHYLIP—phylogeny interference package (version 3.2)
J Felsenstein (1989)
10.1007/BF00177823
Genes for mast-cell serine protease and their molecular evolution
R. Huang (2004)
10.1111/1523-1747.EP12264144
Angiotensin I conversion by human and rat chymotryptic proteinases.
B. Wintroub (1984)
10.1172/JCI117824
Effects of angiotensin II generated by an angiotensin converting enzyme-independent pathway on left ventricular performance in the conscious baboon.
B. Hoit (1995)
Angiotensin II generation by mast cell alpha- and beta-chymases.
G. Caughey (2000)
10.1038/nature02426
Genome sequence of the Brown Norway rat yields insights into mammalian evolution
R. Gibbs (2004)
10.1084/JEM.185.1.13
Secretory Granule Proteases in Rat Mast Cells. Cloning of 10 Different Serine Proteases and a Carboxypeptidase A from Various Rat Mast Cell Populations
C. Lützelschwab (1997)
10.1002/PRO.5560040301
Structural basis of substrate specificity in the serine proteases
J. Perona (1995)
10.1016/s0021-9258(19)40247-0
Identification and molecular cloning of a novel mouse mucosal mast cell serine protease.
W. Serafin (1990)
Genome sequence of the Brown Norway rat yields insights into mammalian
S Cawley (2004)
10.1126/science.271.5248.502
Angiotensin II-Forming Activity in a Reconstructed Ancestral Chymase
U. Chandrasekharan (1996)
10.1016/S0145-305X(03)00084-3
Cloning of IgE from the echidna (Tachyglossus aculeatus) and a comparative analysis of epsilon chains from all three extant mammalian lineages.
M. Vernersson (2004)
10.1093/bioinformatics/13.5.555
PAML: a program package for phylogenetic analysis by maximum likelihood
Z. Yang (1997)
10.1038/23481
Heparin is essential for the storage of specific granule proteases in mast cells
D. Humphries (1999)
10.1016/S0167-4838(00)00076-5
Angiotensin II generation by mast cell α- and β-chymases
G. Caughey (2000)
10.1016/s0021-9258(18)61198-6
Cloning of the mast cell protease, RMCP II. Evidence for cell-specific expression and a multi-gene family.
P. Benfey (1987)
10.1073/PNAS.0501589102
Dramatic variation of the vomeronasal pheromone receptor gene repertoire among five orders of placental and marsupial mammals.
W. Grus (2005)
10.1002/(SICI)1521-4141(199803)28:03<1022::AID-IMMU1022>3.0.CO;2-1
Characterization of mouse mast cell protease‐8, the first member of a novel subfamily of mouse mast cell serine proteases, distinct from both the classical chymases and tryptases
C. Lützelschwab (1998)
10.1074/jbc.272.46.29158
Mouse Mast Cell Protease 9, a Novel Member of the Chromosome 14 Family of Serine Proteases that is Selectively Expressed in Uterine Mast Cells*
J. Hunt (1997)
10.1002/EJI.1830210706
Cloning and structural analysis of MMCP‐1, MMCP‐4 and MMCP‐5, three mouse mast cell‐specific serine proteases
R. Huang (1991)
10.1002/eji.200425429
The genes and gene organization of the Ly49 region of the rat natural killer cell gene complex
Øyvind Nylenna (2005)
Interaction of heparin with rat mast cell protease 1.
G. Pejler (1994)
10.1073/pnas.0334222100
Placental mammal diversification and the Cretaceous–Tertiary boundary
M. Springer (2003)
10.1016/S0022-2836(02)00625-3
The crystal structure of human alpha1-tryptase reveals a blocked substrate-binding region.
U. Marquardt (2002)
10.1093/NAR/25.24.4876
The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools.
J. Thompson (1997)
10.1016/s0021-9258(18)82134-2
A closely linked complex of mouse mast cell-specific chymase genes on chromosome 14.
M. Gurish (1993)
10.1172/JCI114518
Azurocidin and a homologous serine protease from neutrophils. Differential antimicrobial and proteolytic properties.
D. Campanelli (1990)
10.1016/S0014-5793(02)02242-1
Evidence for diversity of substrate specificity among members of the chymase family of serine proteases
S. Solivan (2002)
Codon-substitution models for heterogeneous selection pressure at amino acid sites.
Z. Yang (2000)
10.1093/NAR/28.21.4364
Analysis of canonical and non-canonical splice sites in mammalian genomes.
M. Burset (2000)



This paper is referenced by
10.1007/s00251-010-0443-2
High degree of conservation of the multigene tryptase locus over the past 150–200 million years of mammalian evolution
J. Reimer (2010)
10.1016/j.bcp.2010.06.014
Potency variation of small-molecule chymase inhibitors across species.
J. Kervinen (2010)
10.1371/journal.pone.0154886
Asp-ase Activity of the Opossum Granzyme B Supports the Role of Granzyme B as Part of Anti-Viral Immunity Already during Early Mammalian Evolution
Zhirong Fu (2016)
10.1371/journal.pone.0145592
Correction: Granule Associated Serine Proteases of Hematopoietic Cells – An Analysis of Their Appearance and Diversification during Vertebrate Evolution
Srinivas Akula (2015)
10.1074/jbc.M710502200
Guinea Pig Chymase Is Leucine-specific
G. Caughey (2008)
10.1515/hsz-2014-0174
Analysis of the evolution of granule associated serine proteases of immune defence (GASPIDs) suggests a revised nomenclature
Jamshaid Ahmad (2014)
Mast cell recruitment and activation as measures of cyathostomin burden
Ruth Clements (2015)
10.1111/j.1600-065X.2007.00509.x
Mast cell tryptases and chymases in inflammation and host defense
G. Caughey (2007)
10.1038/ni.2036
Genetic analysis of basophil function in vivo
B. Sullivan (2011)
10.1186/s13059-016-1090-1
Extreme genomic erosion after recurrent demographic bottlenecks in the highly endangered Iberian lynx
F. Abascal (2016)
10.1111/imr.12548
Recent advances in understanding basophil‐mediated Th2 immune responses
Y. Yamanishi (2017)
10.1016/j.molimm.2008.01.012
Extended cleavage specificity of mMCP-1, the major mucosal mast cell protease in mouse-high specificity indicates high substrate selectivity.
M. Andersson (2008)
10.1093/intimm/dxy026
How do basophils contribute to Th2 cell differentiation and allergic responses?
H. Karasuyama (2018)
10.1111/j.1476-5381.2012.02055.x
Chymase inhibition as a pharmacological target: a role in inflammatory and functional gastrointestinal disorders?
S. Heuston (2012)
Cleavage Specificity of Mast Cell Chymases
M. Andersson (2008)
10.1073/pnas.0906372106
Mast cells regulate homeostatic intestinal epithelial migration and barrier function by a chymase/Mcpt4-dependent mechanism
K. Groschwitz (2009)
Production and cleavage specificity determination of serine proteases mMCP-4, mMCP-5, rMCP-2 and two platypus serine proteases of the chymase locus.
C. O. Sidibeh (2013)
10.1093/intimm/dxn128
The extended substrate specificity of the human mast cell chymase reveals a serine protease with well-defined substrate recognition profile.
M. Andersson (2009)
Expressão e caracterização das quimases recombinantes específicas de mastócitos de camundongos (mMCP4 e 5)
Programa de Pós-graduação (2014)
Peptidases in Ancestral Vertebrates-Like Transmembrane γ Evolved from Rapidly during Primate Speciation and Tryptases Changed
George H. Caughey (2007)
10.3390/ijms22010302
Mast Cell Chymase and Kidney Disease
S. Vibhushan (2020)
10.1074/jbc.M116.754648
The Basophil-specific Protease mMCP-8 Provokes an Inflammatory Response in the Skin with Microvascular Hyperpermeability and Leukocyte Infiltration*
Hidemitsu Tsutsui (2016)
10.1093/intimm/dxs081
Extended cleavage specificity of the mast cell chymase from the crab-eating macaque (Macaca fascicularis): an interesting animal model for the analysis of the function of the human mast cell chymase.
M. Thorpe (2012)
10.1093/intimm/dxq021
The extended substrate recognition profile of the dog mast cell chymase reveals similarities and differences to the human chymase.
Maike Gallwitz (2010)
10.3390/ijms20246340
Extended Cleavage Specificities of Rabbit and Guinea Pig Mast Cell Chymases: Two Highly Specific Leu-Ases
Yuan Zhongwei (2019)
10.1371/journal.pone.0195077
Extended cleavage specificity of human neutrophil cathepsin G: A low activity protease with dual chymase and tryptase-type specificities
M. Thorpe (2018)
The mast cell transcriptome and the evolution of granule proteins and Fc receptors
Srinivas Akula (2019)
10.1007/s00251-018-1062-6
Identification and annotation of bovine granzyme genes reveals a novel granzyme encoded within the trypsin-like locus
J. Yang (2018)
10.1074/jbc.M707157200
Structural Basis for Elastolytic Substrate Specificity in Rodent α-Chymases*
J. Kervinen (2008)
10.1515/hsz-2013-0211
Granule proteases of hematopoietic cells, a family of versatile inflammatory mediators - an update on their cleavage specificity, in vivo substrates, and evolution.
L. Hellman (2014)
Hematopoietic Serine Proteases from the Mast Cell Chymase and Tryptase Loci - a Functional and Evolutionary Analysis
J. Reimer (2008)
10.1016/j.ejphar.2015.04.045
Mast cell proteases as pharmacological targets.
G. Caughey (2016)
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