CODON USAGE IN HUMAN MITOCHONDRIAL GENES IN THE CONTEXT OF CANCER
Objective: Mitochondria are the powerhouse of the cell. Mitochondrial DNA is more susceptible to oxidative damage due to the lack of histone protein and chromatin structure. The alteration in the level of gene expression in cytochrome c oxidase gene is associated with cancer. The expression of coxiii gene was found to be lower in human colonic carcinoma. However, a systematic analysis of codon usage in human mitochondrial protein-coding genes has not been reported yet. This study gives an insight into the understanding of the pattern of codon usage and expression in human mitochondrial genes.
Methods: We used a bioinformatics approach to analyse the codon usage parameters by using bioinformatics tools like an effective number of codons (ENC), codon adaptation index (CAI), relative synonymous codon usage (RSCU) etc.
Results: The comparison of codon usage pattern among different mitochondrial genes suggests that mitochondrial genes have a lower level of codon usage bias and high expression level. Highly significant positive correlation between ENC and GC3 (r=0.782**, p<0.01), nucleobases C and C3 (r=0.655*, p<0.05), GC and GC3 (r=0.690**, p<0.01) suggest that mutation pressure played an important role in codon usage bias. Highly significant positive correlation was found between ENC and CAI (r=0.762**, p<0.01). The over-represented codons are TCA, TCC, CTA, CTC, CAA, CGC, TGA, ATA, AAA, GTA, GCC, GAA and GGC while the under-represented codons are TCG, AGT, CTG, CCG, CAG, CGT, ACG, AAT, GTG, GAT, GGG and ATG.
Conclusion: Mutation pressure is found to play major roles in shaping the low bias in the protein-coding genes of human mitochondrial DNA, although codon usage bias is weak. The over-represented and under-represented codons are used to increase or decrease the expression level. In addition, codon usage bias has influenced the gene expression in human mitochondrial genes.
Keywords: Mitochondrial DNA, Synonymous codon usage bias, Gene expression
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