PUBLICATION
Dynamic evolutionary pattern of α2-macroglobulin in a model organism, the zebrafish (Danio rerio)
- Authors
- Padhi, A., Buchheim, M.A., and Verghese, B.
- ID
- ZDB-PUB-080527-2
- Date
- 2008
- Source
- Molecular immunology 45(11): 3312-3318 (Journal)
- Registered Authors
- Keywords
- α2-Macroglobulin, Zebrafish, Phylogeny, Evolution, Gene duplication, Positive selection
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Codon/genetics
- Evolution, Molecular*
- Likelihood Functions
- Molecular Sequence Data
- Phylogeny
- Sequence Alignment
- Zebrafish/genetics*
- alpha-Macroglobulins/chemistry
- alpha-Macroglobulins/genetics*
- PubMed
- 18485482 Full text @ Mol. Immunol.
Citation
Padhi, A., Buchheim, M.A., and Verghese, B. (2008) Dynamic evolutionary pattern of α2-macroglobulin in a model organism, the zebrafish (Danio rerio). Molecular immunology. 45(11):3312-3318.
Abstract
Studies of alpha-2-macroglobulin (alpha(2)M), a universal protease inhibitor, have indicated that it plays a unique and critical role in the innate immune system of vertebrate and invertebrate animals. The distinctive mechanism of pathogen inhibition - through physical entrapment of the pathogen-derived protease - makes alpha(2)M an ideal candidate for molecular evolutionary analysis. Furthermore, recent studies revealed that the Osteichthyes are characterized by levels of alpha(2)M diversification that exceed those recorded in other animal groups. Our study of Danio rerio (zebrafish) indicated that (1) two distinct lineages of alpha(2)M and alpha(2)M-like isoforms exist and (2) at least some codons in the functional domains of alpha(2)M have been subjected to positive Darwinian selection. The findings of several hot-spots for nonsynonymous substitutions in the two functional domains such as bait region and receptor binding domain, suggest that host-immune selection have played a dominant role in these two genomic regions of alpha(2)M. The presence of two, non-monophyletic alpha(2)M lineages in zebrafish provides compelling evidence of an ancient gene duplication event. The accelerated rate of nucleotide substitution in the functional domains of alpha(2)M is consistent with similar observations of other immune system components.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping