whole genome sequencing and evolutionary analysis of human papillomavirus type 16 in central china全基因组测序及进化分析人类乳头瘤病毒16型.pdf

Whole Genome Sequencing and Evolutionary Analysis of Human Papillomavirus Type 16 in Central China 1. 1. 1 1 1 1 1 1 Min Sun , Lei Gao , Ying Liu , Yiqiang Zhao , Xueqian Wang , Yaqi Pan , Tao Ning , Hong Cai , 3 2 1 Haijun Yang , Weiwei Zhai *, Yang Ke * 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital Institute, Beijing, China, 2 Center for Computational Biology and Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China, 3 Anyang Cancer Hospital, Anyang, Henan, China Abstract Human papillomavirus type 16 plays a critical role in the neoplastic transformation of cervical cancers. Molecular variants of HPV16 existing in different ethnic groups have shown substantial phenotypic differences in pathogenicity, immunogenicity and tumorigenicity. In this study, we sequenced the entire HPV16 genome of 76 isolates originated from Anyang, central China. Phylogenetic analysis of these sequences identified two major variants of HPV16 in the Anyang area, namely the European prototype (E(p)) and the European Asian type (E(As)). These two variants show a high degree of divergence between groups, and the E(p) comprised higher genetic diversity than the E(As). Analysis with two measurements of genetic diversity indicated that viral population size was relatively stable in this area in the past. Codon based likelihood models revealed strong statistical support for adaptive evolution acting on the E6 gene. Bayesian analysis identified several important amino acid positions that may be driving adaptiv