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12:54
Transient Expression of Proteins by Hydrodynamic Gene Delivery in Mice
Published on: May 5, 2014
Mutational dynamics of murine angiogenin duplicates
Francisco M Codoñer1, Silvia Alfonso-Loeches, Mario A Fares
1Evolutionary Genetics and Bioinformatics Laboratory, Department of Genetics, Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin, Ireland.
BMC Evolutionary Biology
|October 19, 2010
Summary
Angiogenin (Ang) protein variability in mammals, particularly in mice, suggests functional divergence after gene duplication. This highlights Ang plasticity but cautions against using mouse models for human Ang mutation studies.
Area of Science:
- Evolutionary biology
- Genomics
- Biochemistry
Background:
- Angiogenin (Ang) is crucial for blood vessel formation and linked to cancer and neurodegenerative diseases.
- Despite evolutionary constraints, Ang shows significant sequence variability across species.
- The adaptive value of Ang variability and functional divergence in paralogs remains unclear.
Purpose of the Study:
- Investigate the evolutionary dynamics and functional divergence of Ang paralogs in mammals.
- Understand the relationship between mutations and Ang function, especially in mouse and rat.
- Test the hypothesis of adaptive value in Ang variability.
Main Methods:
- Phylogenetic analysis of Ang gene copies in mice and rats within vertebrate Ang phylogeny.
- Identification of amino acid sites under selection, focusing on signal localization and nucleotide binding.
- 3D structural modeling of murine Ang (mAng) paralogs.
Main Results:
- Evidence of accelerated evolution in some murine Ang (mAng) copies, without loss of function.
- Amino acid sites involved in Ang's signal localization and nucleotide binding evolved under diversifying selection.
- Mutations suggest functional divergence in mAng paralogs, supported by structural similarities indicating functional rather than non-functional changes.
Conclusions:
- Identified key evolutionary dynamics shaping Ang variability and plasticity post-gene duplication.
- Demonstrated functional divergence among mAng paralogs, making them a model for studying protein plasticity.
- Caution advised when extrapolating mouse Ang mutation effects to human single-copy Ang.
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