Codon usage bias and A+T content variation in human papillomavirus genomes.

We analyzed the codon usage bias of eight open reading frames (ORFs) across up to 79 human papillomavirus (HPV) genotypes from three distinct phylogenetic groups. All eight ORFs across HPV genotypes show a strong codon usage bias, amongst degenerately encoded amino acids, toward 18 codons mainly with T at the 3rd position. For all 18 degenerately encoded amino acids, codon preferences amongst human and animal PV ORFs are significantly different from those averaged across mammalian genes. Across the HPV types, the L2 ORFs show the highest codon usage bias (73.2+/-1.6% and the E4 ORFs the lowest (51.1+/-0.5%), reflecting as similar bias in codon 3rd position A+T content (L2: 76.1+/-4.2%; E4: 58.6+/-4.5%). The E4 ORF, uniquely amongst the HPV ORFs, is G+C rich, while the other ORFs are A+T rich. Codon usage bias correlates positively with A+T content at the codon 3rd position in the E2, E6, L1 and L2 ORFs, but negatively in the E4 ORFs. A general conservation of preferred codon usage across human and non-human PV genotypes whether they originate from a same supergroup or not, together with observed difference between the preferred codon usage for HPV ORFs and for genes of the cells they infect, suggests that specific codon usage bias and A+T content variation may somehow increase the replicational fitness of HPVs in mammalian epithelial cells, and have practical implications for gene therapy of HPV infection.