Is there codon usage bias for poly-Q stretches in the human proteome?

Area of Science:

• Genomics
• Proteomics
• Bioinformatics

Background:

• Poly-glutamine (poly-Q) stretches are protein regions rich in the amino acid glutamine.
• These regions are implicated in various human diseases and can adopt disordered structures.
• Understanding codon usage patterns in poly-Q stretches is crucial for deciphering protein function and disease mechanisms.

Purpose of the Study:

• To investigate codon usage patterns in poly-Q stretches of varying lengths within the human proteome.
• To determine the structural characteristics of long poly-Q stretches.
• To compare codon usage biases in poly-Q repeats between the general human proteome and disease-associated proteins.

Main Methods:

• Analysis of codon usage for poly-Q stretches from the Protein Data Bank (PDB) and the HraDis database.
• Identification and characterization of disordered regions associated with poly-Q stretches.
• Statistical analysis of codon bias and correlation with splicing sites.

Main Results:

• All long poly-Q stretches identified in the PDB are located within disordered protein regions.
• A significant bias towards the CAG codon for glutamine homo-repeats was observed in the human proteome.
• Disease-associated proteins showed a slightly lower frequency (22%) of identical codon usage in poly-Q repeats compared to the general human proteome (26%).
• Splicing sites were found to correspond to homo-repeats in 28 cases and at the N-terminal part of homo-repeats in 11 cases with statistical significance.

Conclusions:

• Poly-Q stretches in the human proteome are predominantly disordered and exhibit specific codon usage biases.
• The CAG triplet is the preferred codon for glutamine homo-repeats.
• Alterations in codon usage bias within poly-Q repeats may be associated with disease states.
• The association of splicing sites with poly-Q homo-repeats suggests a potential regulatory role in gene expression.