A universal nonmonotonic relationship between gene compactness and expression levels in multicellular eukaryotes.

Area of Science:

• Comparative genomics
• Gene regulation
• Molecular evolution

Background:

• Gene architecture, including length and compactness, is crucial for cellular function.
• The relationship between gene expression and its structural properties is not fully understood.
• Two main hypotheses, selection and genomic design, attempt to explain gene compactness.

Purpose of the Study:

• To investigate the universal relationship between gene expression level and gene compactness.
• To test the validity of the selection hypothesis versus the genomic design hypothesis.
• To explore the correlation between gene expression breadth and gene compactness.

Main Methods:

• Analysis of gene architecture and expression levels in four diverse organisms: Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, and Arabidopsis thaliana.
• Statistical analysis to determine the relationship between expression level, expression breadth, and gene compactness.
• Comparison of observed correlations with predictions from the selection and genomic design hypotheses.

Main Results:

• A non-monotonic, bell-shaped relationship was discovered between gene expression level and gene compactness.
• Highly expressed genes exhibit increased compactness, while moderately expressed genes are longer.
• Gene expression level showed a stronger correlation with gene compactness than expression breadth in humans.

Conclusions:

• The findings support the selection hypothesis, suggesting expression level is a primary driver of gene compactness.
• Gene elongation at lower expression levels may be due to regulatory element accumulation.
• Highly expressed genes likely become compact due to selection for efficient transcription, splicing, and translation.