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Nonrandom intragenic variations in patterns of codon bias implicate a sequential interplay between transitional
1Institute of Molecular and Cell Biology, Bioinformatics Centre, National University of Singapore, 117609, Singapore.
Journal of Molecular Evolution
|January 24, 2004
Summary
Codon bias in human genes is not random. Guanine and cytosine content (GC3) varies within genes, reflecting domain function and amino acid properties, suggesting selection shapes DNA sequences.
Area of Science:
- Genomics and Molecular Biology
- Bioinformatics
- Protein Structure and Function
Background:
- Synonymous codons exhibit nonrandom distribution (codon bias) in human and other genes.
- The functional significance of codon third bases is often considered minimal, yet their distribution is nonrandom.
Purpose of the Study:
- To investigate intragenic codon bias in human transmembrane cell-surface receptor proteins.
- To determine if codon bias correlates with receptor domain type, amino acid properties, and receptor class.
Main Methods:
- Generated a database of DNA sequences for human transmembrane cell-surface receptor proteins.
- Analyzed guanine and cytosine content at codon third positions (GC3) across different receptor domains and amino acid types.
- Utilized nearest-neighbor analysis to examine base-pair preferences at specific sequence positions.
Main Results:
- GC3 content varied intragenically with receptor domain (transmembrane > extracellular > intracellular) and amino acid phenotype (hydrophobic > hydrophilic > neutral).
- GC3 declined within transmembrane domains as functionality became redundant with increasing hydrophobicity.
- Evidence suggests positive selection favors transitional mutations (XCG to XTG) for hydrophobic amino acids in transmembrane domains.
Conclusions:
- Intragenic codon bias patterns reflect a balance between negative and positive selection.
- Analysis of codon third-base usage can potentially predict the functional significance of encoded protein products.