Affiliation:
1. Department of Zoology and Genetics, Center for Bioinformatics and Biological Statistics, Iowa State University, Ames, Iowa 50011
Abstract
Abstract
In this article, we explore the pattern of type I functional divergence (i.e., altered functional constraints or site-specific rate difference) in the caspase gene family that is important for apoptosis (programmed cell death) and cytokine maturation. By taking advantage of substantial experimental data from caspases, the functional/structural basis of our posterior predictions from sequence analysis was extensively studied. Our results are as follows: (1) Phylogenetic analysis shows that the evolution of major caspase-mediated pathways has been facilitated by gene duplications, (2) type I functional divergence (altered functional constraints) is statistically significant between two major subfamilies, CED-3 and ICE, (3) 4 of 21 predicted amino acid residues (for site-specific rate difference between CED-3 and ICE) have been verified by experimental evidence, and (4) we found that some CED-3 caspases may inherit more ancestral functions, whereas other members may employ some recently derived functions. Our approach can be cost effective in functional genomics to make statistically sound predictions from amino acid sequences.
Publisher
Oxford University Press (OUP)
Reference41 articles.
1. The domains of death: evolution of the apoptosis machinery;Aravind;Trends Biochem. Sci.,1999
2. Defects in regulation of apoptosis in caspase-2-deficient mice;Bergeron;Genes Dev.,1998
3. Biochemical pathways of caspase activation during apoptosis;Budihardjo;Annu. Rev. Cell. Dev. Biol.,1999
4. A method to predict functional residues in proteins;Casari;Nat. Struct. Biol.,1995
5. B cell apoptosis triggered by antigen receptor ligation proceeds via a novel caspase-dependent pathway;Chen;J. Immunol.,1999
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