Get access

Recombination and natural selection in hepatitis E virus genotypes


  • Xiaoming Chen, Qian Zhang, Chao He, Lei Zhang, Jinghua Li, Weilu Zhang, Wei Cao, Yong-Gang Lv, and Zhengcai Liu contributed equally to this work.


To gain new insights into the evolutionary processes that created the genetic diversity of the hepatitis E virus (HEV), the Recombination Detection Program (RDP) and SimPlot program were employed to detect recombination events in the genome, then the fixed-effects likelihood (FEL) method was used to detect natural selection effects on viral proteins. Recombination analysis provided strong evidence for both intergenotype and intragenotype recombination events in the sequences analyzed. Recombination events were found to be distributed non-randomly, with the highest frequency in the X domain and the helicase. Strain DQ450072 was identified as intergenotype-recombinant. Natural selection analysis revealed that codons under both negative selection and positive selection were distributed non-randomly. ORF1 and ORF2 have experienced strong purifying selection across genotypes. Furthermore, potentially important sites were also found under positive selection in the N-terminal end of ORF2 and the C-terminal end of ORF3. No significant difference was found among the selective pressures on different genotypes. J. Med. Virol. 84:1396–1407, 2012. © 2012 Wiley Periodicals, Inc.