MBE Advance Access published online on February 14, 2008
Molecular Biology and Evolution, doi:10.1093/molbev/msn012
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Research Article |
Identification of novel mammalian caspases reveals an important role of gene loss in shaping the human caspase repertoire
1 Department of Dermatology, Medical University of Vienna, Vienna, Austria
2 Max F. Perutz Laboratories, Medical University of Vienna, Vienna, Austria
3 Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA
4 Department for Farm Animals and Herd Management, University of Veterinary Medicine Vienna, Vienna, Austria
5 College of Veterinary Medicine, University of Sulaimani, Sulaimani, Iraq
Corresponding author: Leopold Eckhart, Medical University of Vienna, Department of Dermatology, Waehringer Guertel 18-20, 1090 Vienna, Austria, Tel. 1-40400-5833; Fax: 43-1-40400-5167; E-mail: leopold.eckhart{at}meduniwien.ac.at
Received for publication December 5, 2007. Accepted for publication January 7, 2008.
Proteases of the caspase family play central roles in apoptosis and inflammation. Recently we have described a new gene encoding caspase-15 which has been inactivated independently in different mammalian lineages. To determine the dynamics of gene duplication and loss in the entire caspase gene family, we performed a comprehensive evolutionary analysis of mammalian caspases. By comparative genomics and RT-PCR analyses, we identified three novel mammalian caspase genes, which we tentatively named caspases-16 through 18. Caspase-16, which is most similar in sequence to caspase-14, has been conserved in marsupials and placental mammals, including humans. Caspase-17, which is most similar to caspase-3, has been conserved among fish, frog, chicken, lizard and the platypus, but is absent from marsupials and placental mammals. Caspase-18, which is most similar to caspase-8, has been conserved among chicken, platypus and opossum, but is absent from placental mammals. These gene distribution patterns suggest that, in the evolutionary lineage leading to humans, caspase-17 was lost after the split of protherian and therian mammals, and caspase-18 was lost after the split of marsupials and placental mammals. In the canine genome the number of caspases has been reduced by the fusion of the neighboring genes caspase-1 and 4, resulting in a single coding region. Further lineage-specific gene inactivations were found for caspase-10 in murine rodents, and caspase-12 in humans, rabbit and cow. Lineage-specific gene duplications were found for caspases-1, 3 and 12 in opossum and caspase-4 in primates. Other caspases were generally conserved in all mammalian species investigated. Using the positions of introns as stable characters during recent vertrebrate evolution, we define three phylogenetic clades of caspase genes: caspase-1/2/4/5/9/12/14/15/16 (clade I), caspase-3/6/7/17 (clade II), and caspase-8/10/18/CFLAR (clade III). We conclude that gene inactivations have occurred in each of the three caspase clades and that gene loss has been as critical as gene duplication in the evolution of the human repertoire of caspases.
Key Words: caspase • gene loss • gene duplication • comparative genomics • mammals