Cytochrome P450 genes in coronary artery diseases: Codon usage analysis reveals genomic GC adaptation

• Cytochrome P450 (CYP) genes affecting coronary artery diseases (CAD) are GC rich at third codon position.
• Effective number of codons (Nc) showed negative correlation with GC3 content.
• Dinucleotides CG and TA are under-represented but TG and CA are over-represented in coding sequences.
• Both mutation pressure and natural selection are responsible for codon usage bias of CYP genes.
• Purifying selection has acted on 1st and 2nd position of codons.

Establishing codon usage biases are imperative for understanding the etiology of coronary artery diseases (CAD) as well as the genetic factors associated with these diseases. The aim of this study was to evaluate the contribution of 18 responsible cytochrome P450 (CYP) genes for the risk of CAD. Effective number of codon (Nc) showed a negative correlation with both GC3 and synonymous codon usage order (SCUO) suggesting an antagonistic relationship between codon usage and Nc of genes. The dinucleotide analysis revealed that CG and TA dinucleotides have the lowest odds ratio in these genes. Principal component analysis showed that GC composition has a profound effect in separating the genes along the first major axis. Our findings revealed that mutational pressure and natural selection could possibly be the major factors responsible for codon bias in these genes. The study not only offers an insight into the mechanisms of genomic GC adaptation, but also illustrates the complexity of CYP genes in CAD.