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Domain deletions and substitutions in the modular protein evolution.
January Weiner1, Francois Beaussart, Erich Bornberg-Bauer
1Division of Bioinformatics, School of Biological Sciences, The Westfalian Wilhelms University of Münster, Germany.
The FEBS Journal
|April 28, 2006
Summary
Protein domain loss, particularly at the ends, is a key evolutionary mechanism. This study reveals how terminal domain loss is facilitated by start/stop codons, influencing protein evolution.
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Bioinformatics
Background:
- Protein modularity arises from gene duplication, fusion, fission, recombination, and fragment loss.
- Previous research emphasized duplications and fusions, with less focus on domain loss mechanisms.
Purpose of the Study:
- To investigate the mechanisms and patterns of protein domain loss.
- To analyze the role of domain arrangement in protein evolution.
Main Methods:
- Utilized motif databases to study protein domain arrangements.
- Developed a protein similarity measure based on domain strings and dynamic alignment.
- Analyzed domain loss and duplication frequencies at different protein regions.
Main Results:
- Domain losses and duplications are more frequent at protein termini.
- Terminal domain loss is facilitated by start/stop codons, reducing negative selection.
- Domains also found as single-domain proteins are less prone to loss in N-terminal and middle regions.
- Domain substitutions are rare, especially in internal protein regions.
- Identified erroneous annotations as a source of apparent domain loss/substitution.
Conclusions:
- Fission/fusion events involving single-domain proteins primarily occur at the C-terminus.
- Domain loss is a significant evolutionary process, particularly at protein ends, driven by genetic mechanisms.
- Evolutionary trajectories of domain loss can be traced, as exemplified by bacterial formate dehydrogenases.