caa a22 4500 467907579 CHVBK 20180406152839.0 cr unu---uuuuu 170328e20060801xx s 000 0 eng 10.1007/s00251-006-0123-4 doi (NATIONALLICENCE)springer-10.1007/s00251-006-0123-4 Rapid lineage-specific diversification of the mast cell chymase locus during mammalian evolution [Elektronische Daten] [Maike Gallwitz, Lars Hellman] 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 95Myr 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. Springer-Verlag, 2006 Mammalian evolution nationallicence Gene duplication nationallicence Chymase locus nationallicence Mast cell nationallicence Gallwitz Maike Department of Cell and Molecular Biology, Program for Immunology, Uppsala University, Box 596, BMC, 75124, Uppsala, Sweden aut Hellman Lars Department of Cell and Molecular Biology, Program for Immunology, Uppsala University, Box 596, BMC, 75124, Uppsala, Sweden aut Immunogenetics Springer-Verlag 58/8(2006-08-01), 641-654 0093-7711 58:8<641 2006 58 251 https://doi.org/10.1007/s00251-006-0123-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00251-006-0123-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gallwitz Maike Department of Cell and Molecular Biology, Program for Immunology, Uppsala University, Box 596, BMC, 75124, Uppsala, Sweden aut NATIONALLICENCE 700 1- Hellman Lars Department of Cell and Molecular Biology, Program for Immunology, Uppsala University, Box 596, BMC, 75124, Uppsala, Sweden aut NATIONALLICENCE 773 0- Immunogenetics Springer-Verlag 58/8(2006-08-01), 641-654 0093-7711 58:8<641 2006 58 251 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer