PUBLICATION
The dystrotelin, dystrophin and dystrobrevin superfamily: new paralogues and old isoforms
- Authors
- Jin, H., Tan, S., Hermanowski, J., Bohem, S., Pacheco, S., McCaule, J.M., Greener, M.J., Hinits, Y., Hughes, S.M., Sharpe, P.T., Roberts, R.G.,
- ID
- ZDB-PUB-070125-1
- Date
- 2007
- Source
- BMC Genomics 8(1): 19 (Journal)
- Registered Authors
- Hinits, Yaniv, Hughes, Simon M.
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Drosophila
- Drosophila Proteins/chemistry*
- Dystrophin/chemistry*
- Dystrophin/genetics
- Dystrophin-Associated Proteins/chemistry*
- Expressed Sequence Tags
- Humans
- Membrane Proteins/chemistry*
- Mice
- Molecular Sequence Data
- Multigene Family
- Promoter Regions, Genetic
- Protein Isoforms*
- Sequence Homology, Amino Acid
- Zebrafish
- PubMed
- 17233888 Full text @ BMC Genomics
Citation
Jin, H., Tan, S., Hermanowski, J., Bohem, S., Pacheco, S., McCaule, J.M., Greener, M.J., Hinits, Y., Hughes, S.M., Sharpe, P.T., Roberts, R.G., (2007) The dystrotelin, dystrophin and dystrobrevin superfamily: new paralogues and old isoforms. BMC Genomics. 8(1):19.
Abstract
Dystrophins and dystrobrevins are distantly related proteins with important but poorly understood roles in the function of metazoan muscular and neuronal tissues. Defects in them and their associated proteins cause a range of neuromuscular disorders. Members of this superfamily have been discovered in a relatively serendipitous way; we set out to compile a comprehensive description of dystrophin- and dystrobrevin-related sequences from available metazoan genome sequences, validated in representative organisms by RT-PCR, or acquired de novo from key species. RESULTS: Features of the superfamily revealed by our survey include: a) Dystrotelin, an entirely novel branch of the superfamily, present in most vertebrates examined. Dystrotelin is expressed in the central nervous system, and is a possible orthologue of Drosophila DAH. We describe the preliminary characterisation of its function, evolution and expression. b) A novel vertebrate member of the dystrobrevin family, gamma-dystrobrevin, an ancient branch now extant only in fish, but probably present in our own ancestors. Like dystrophin, zebrafish gamma-dystrobrevin mRNA is localised to myosepta. c) The extent of conservation of alternative splicing and alternative promoter use in the dystrophin and dystrobrevin genes; alternative splicing of dystrophin exons 73 and 78 and alpha-dystrobrevin exon 13 are conserved across vertebrates, as are the use of the Dp116, Dp71 and G-utrophin promoters; the Dp260 and Dp140 promoters are tetrapod innovations. d) The evolution of the unique N-terminus of DRP2 and its relationship to Dp116 and G-utrophin. e) A C-terminally truncated common ancestor of dystrophin and utrophin in cyclostomes. f) A severely restricted repertoire of dystrophin complex components in ascidians. CONCLUSIONS: We have refined our understanding of the evolutionary history and isoform diversity of the five previously reported vertebrate superfamily members and describe two novel members, dystrotelin and gamma-dystrobrevin. Dystrotelins, dystrophins and dystrobrevins are roughly equally related to each other. Vertebrates therefore have a repertoire of seven superfamily members (three dystrophins, three dystrobevins, and one dystrotelin), with one lost in tetrapods. Most invertebrates studied have one member from each branch. Although the basic shared function which is implied by the common architecture of these distantly related proteins remains unclear, it clearly permeates metazoan biology.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping