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Published on: July 14, 2015
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Reassessing the "duon" hypothesis of protein evolution
1State Key Laboratory of Biocontrol, Cooperative Innovation Center for High Performance Computing, College of Ecology and Evolution, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China xingk@mail.sysu.edu.cn.
Molecular Biology and Evolution
|January 14, 2015
Summary
The "duon" hypothesis suggested protein-coding DNA sequences regulate gene expression. Our reanalysis found no evidence of extra selection on these codons, challenging this idea.
Area of Science:
- Genomics
- Molecular Biology
- Evolutionary Biology
Background:
- Genomes contain coding and regulatory DNA sequences.
- A recent hypothesis proposed protein-coding sequences also regulate gene expression via transcription factor (TF) occupancy.
- This
- duon
- hypothesis suggested up to 15% of human gene codons are constrained by TF binding.
Purpose of the Study:
- To reanalyze data supporting the
- duon
- hypothesis.
- To investigate the evolutionary constraints on codons occupied by transcription factors.
Main Methods:
- Reanalyzed existing transcription factor occupancy data from human cells.
- Conducted an unbiased comparison of codon conservation, separating G/C and A/T sites.
- Assessed purifying selection on TF-bound versus TF-depleted codons.
Main Results:
- Identified ascertainment bias related to base composition in the original study.
- Revealed similar conservation levels between TF-bound and TF-depleted codons.
- Found no significant extra purifying selection on codons due to TF occupancy.
Conclusions:
- The
- duon
- hypothesis is not supported by unbiased analysis.
- Transcription factor occupancy on protein-coding sequences appears largely passive and evolutionarily neutral.
- The functional role of TF occupancy on coding sequences requires further investigation.
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