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Updated: Aug 30, 2025
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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
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Similar protein segments shared between domains of different evolutionary lineages
Kaiyu Qiu1, Nir Ben-Tal1, Rachel Kolodny2
1Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Protein Science : a Publication of the Protein Society
|August 30, 2022
Summary
Novel protein evolution may occur through reused segments, not just domain duplication. Researchers found nearly 500 "bridging themes" linking ancient protein domains, suggesting flexible segments aid evolutionary innovation.
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Biochemistry
Background:
- The origin of novel protein domains is a key question in molecular evolution.
- While domain duplication and recombination are known mechanisms, the emergence of entirely new protein structures is less understood.
- De novo emergence from random sequences is improbable due to the low likelihood of functional folding.
Purpose of the Study:
- To investigate the hypothesis that novel proteins arise from the duplication and fusion of pre-existing polypeptide segments.
- To identify and characterize short, shared segments (bridging themes) within proteins that may represent remnants of ancient evolutionary events.
- To expand the catalog of identified bridging themes, particularly those linking ancient protein folds.
Main Methods:
- Employed a specialized search strategy to detect short, shared sequence segments (themes) between protein domains.
- Explicitly searched for themes where flanking sequence segments (before and after the theme) exhibit significant sequence and structural dissimilarity.
- Expanded upon a previously developed search methodology to discover additional bridging themes.
Main Results:
- Discovered nearly 500 new bridging themes, significantly expanding the known instances of such segments.
- These themes link protein domains, often those belonging to ancient folds.
- The identified themes, averaging 53 residues, demonstrate substantial sequence identity (37% on average) but do not consistently retain their structure, suggesting conformational flexibility.
Conclusions:
- Bridging themes provide evidence for the emergence of novel proteins through the reuse and recombination of smaller polypeptide segments.
- Conformational flexibility of these themes may be an evolutionary advantage, allowing them to integrate into diverse protein environments.
- The findings offer insights into the evolutionary pathways of protein domain emergence and diversification.
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