PUBLICATION
Functional divergence in teleost cardiac troponin paralogs guides variation in the interaction of TnI switch region with TnC
- Authors
- Genge, C.E., Stevens, C.M., Davidson, W.S., Singh, G., Tieleman, D.P., Tibbits, G.F.
- ID
- ZDB-PUB-160317-10
- Date
- 2016
- Source
- Genome biology and evolution 8(4): 994-1011 (Journal)
- Registered Authors
- Keywords
- functional divergence, molecular co-evolution, protein interaction, regulatory sub-functionalization, structural sub-functionalization, troponin
- MeSH Terms
-
- Acclimatization
- Amino Acid Sequence
- Animals
- Cold Temperature
- Evolution, Molecular*
- Gene Expression Profiling
- Models, Molecular
- Phylogeny
- Protein Interaction Maps
- Selection, Genetic
- Troponin C/analysis
- Troponin C/genetics*
- Troponin C/metabolism
- Troponin I/analysis
- Troponin I/genetics*
- Troponin I/metabolism
- Zebrafish/genetics*
- Zebrafish/physiology
- PubMed
- 26979795 Full text @ Genome Biol. Evol.
Citation
Genge, C.E., Stevens, C.M., Davidson, W.S., Singh, G., Tieleman, D.P., Tibbits, G.F. (2016) Functional divergence in teleost cardiac troponin paralogs guides variation in the interaction of TnI switch region with TnC. Genome biology and evolution. 8(4):994-1011.
Abstract
Gene duplication results in extra copies of genes that must co-evolve with their interacting partners in multimeric protein complexes. The cardiac troponin (Tn) complex, containing TnC, TnI and TnT, forms a distinct functional unit critical for the regulation of cardiac muscle contraction. In teleost fish, the function of the Tn complex is modified by the consequences of differential expression of paralogs in response to environmental thermal challenges. In this paper, we focus on the interaction between TnI and TnC, coded for by genes that have independent evolutionary origins, but the co-operation of their protein products has necessitated coevolution. In this study we characterize functional divergence of TnC and TnI paralogs, specifically the inter-related roles of regulatory sub-functionalization and structural sub-functionalization.We determined that differential paralog transcript expression in response to temperature acclimation results in three combinations of TnC and TnI in the zebrafish heart: TnC1a/TnI1.1; TnC1b/TnI1.1 and TnC1a/TnI1.5. Phylogenetic analysis of these highly conserved proteins identified functionally divergent residues in TnI and TnC. The structural and functional effect of these Tn combinations was modeled with molecular dynamics simulation to link divergent sites to changes in interaction strength. Functional divergence in TnI and TnC were not limited to the residues involved with TnC/TnI switch interaction, which emphasizes the complex nature of Tn function. Patterns in domain-specific divergent selection and interaction energies suggest that substitutions in the TnI switch region are crucial to modifying TnI/TnC function to maintain cardiac contraction with temperature changes. This integrative approach introduces Tn as a model of functional divergence that guides the co-evolution of interacting proteins.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping