engleski

Could codon usage influence HPV pathogenesis?

The standard genetic code has 61 sense codons coding for 20 amino acids during protein synthesis. This large degeneracy leads to several different codons standing for the same amino acid and during evolution different organisms have diverged in their codon preference for individual amino acids. In addition, mechanisms have evolved which utilize this codon information to finely tune protein expression for particular purposes by using different codons in specific context without changing the protein sequence. It is already known that HPV genome has different codon usage than the human genome, and it was experimentally shown that codon optimised HPV genes lead to greater protein expression in keratinocytes even though mRNA levels stay the same. One of the hypotheses to explain the different codon usage of HPV versus host was that HPV intentionally reduces its protein expression to avoid the immune system. Therefore, we conducted a bioinformatical analysis to determine whether there are significant differences in codon usage among high (HR) and low-risk (LR) HPV types to further strengthen the current hypothesis. To this end we have analysed coding sequences for all early and late genes of epidemiologically determined or phylogenetically associated HR, LR and undetermined risk alpha genus HPV types. Human codon usage information was taken from online codon usage database or determined from coding sequences of human ribosomal protein genes or genes of the epidermal differentiation complex. We have applied two different programme packages and measured several different measures of codon usage bias. Our results indicate that there is highly statistically significant difference (t-test, p<0.0001) in both the overall codon usage and individual gene codon usage among HR and LR alpha genus HPV types.

codon usage; human papillomavirus

nije evidentirano