Identification of novel mammalian caspases reveals an important role of gene loss in shaping the human caspase repertoire

Leopold Eckhart, Claudia Ballaun, Marcela Hermann, John L. VandeBerg, Wolfgang Sipos, Aumaid Uthman, Heinz Fischer, Erwin Tschachler

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Proteases of the caspase family play central roles in apoptosis and inflammation. Recently, we have described a new gene encoding caspase-15 that 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 reverse transcriptase-polymerase chain reaction analyses, we identified 3 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 caspases-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 vertebrate evolution, we define 3 phylogenetic clades of caspase genes: caspases-1/-2/-4/-5/-9/-12/-14/-15/-16 (clade I), caspases-3/-6/-7/-17 (clade II), and caspases-8/-10/-18/CFLAR (clade III). We conclude that gene inactivations have occurred in each of the 3 caspase clades and that gene loss has been as critical as gene duplication in the evolution of the human repertoire of caspases.

Original languageEnglish (US)
Pages (from-to)831-841
Number of pages11
JournalMolecular Biology and Evolution
Volume25
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

Fingerprint

caspases
Caspases
Genes
gene
genes
Mammals
mammal
marsupial
caspase-1
Marsupialia
Caspase 3
Caspase 1
Gene Duplication
mammals
Caspase 10
Platypus
gene duplication
Metatheria
Opossums
caspase-8

Keywords

  • Caspase
  • Comparative genomics
  • Gene duplication
  • Gene loss
  • Mammals

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Biochemistry
  • Genetics(clinical)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences (miscellaneous)

Cite this

Eckhart, L., Ballaun, C., Hermann, M., VandeBerg, J. L., Sipos, W., Uthman, A., ... Tschachler, E. (2008). Identification of novel mammalian caspases reveals an important role of gene loss in shaping the human caspase repertoire. Molecular Biology and Evolution, 25(5), 831-841. https://doi.org/10.1093/molbev/msn012

Identification of novel mammalian caspases reveals an important role of gene loss in shaping the human caspase repertoire. / Eckhart, Leopold; Ballaun, Claudia; Hermann, Marcela; VandeBerg, John L.; Sipos, Wolfgang; Uthman, Aumaid; Fischer, Heinz; Tschachler, Erwin.

In: Molecular Biology and Evolution, Vol. 25, No. 5, 05.2008, p. 831-841.

Research output: Contribution to journalArticle

Eckhart, L, Ballaun, C, Hermann, M, VandeBerg, JL, Sipos, W, Uthman, A, Fischer, H & Tschachler, E 2008, 'Identification of novel mammalian caspases reveals an important role of gene loss in shaping the human caspase repertoire', Molecular Biology and Evolution, vol. 25, no. 5, pp. 831-841. https://doi.org/10.1093/molbev/msn012
Eckhart, Leopold ; Ballaun, Claudia ; Hermann, Marcela ; VandeBerg, John L. ; Sipos, Wolfgang ; Uthman, Aumaid ; Fischer, Heinz ; Tschachler, Erwin. / Identification of novel mammalian caspases reveals an important role of gene loss in shaping the human caspase repertoire. In: Molecular Biology and Evolution. 2008 ; Vol. 25, No. 5. pp. 831-841.
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