Comparative Structural and Functional Analysis of E6 Oncogene of Human Papillomavirus Type 16.

ABSTRACT

Human papillomavirus (HPV) is an etiologic agent of the uterine cervix cancer and several other neoplasias in women globally. E6 protein of HPV type 16 is highly conserved and plays the key role in an inducing cancer via suppressing activity of P53. We have used different bioinformatics tools for generation of phylogenetic tree, modeling of RNA secondary structure, gene designing and codon optimization of HPV E6 gene. The size of E6 gene sequences of nine strains HPV type 16 was estimated to be 456 to 477 bp and G+C content was ranged between 37.06 to 37.94%. We used E6 gene sequences for construction of phylogenetic relationship and these divided into five groups. RNA secondary structures of E6 gene were modeled and analyzed that folding free energy of wild genes was -093.96, -106.21,-040.48, -090.76, - 072.68, -092.86, -039.32, -044.78, -047.88 kcal/mol and after codon optimization free energy was -122.70, -107.40, - 104.80, -121.40, -127.40, -110.80, -105.20, -122.30, -110.40 kcal/mol respectively. Moreover, gene designing and codon optimization have used to improve the heterologous expression in living organisms by increasing translational efficiency. All strains of HPV16 were used for codon optimization in E. coli. Codon adaptation index (CAI) and G+C contents of E6 gene in optimized DNA were enhanced by 3.6 (72.7%) and 1.3 (25.2%) fold, respectively. The present study provides useful insights into phylogenetic and evolution in the cervical cancer causing Human papillomavirus type 16. The optimized DNA can be chemically synthesized and over expressed in E. coli as compare to its wild type counterparts. Alternatively, the secondary structure and free energy of E6 were investigated that will be helpful to predict the evolution of primitive and genetically stable HPV type 16 strains. This finding provides new insight in better understanding of cervical cancer.