Evolutionary History of Hepatitis E Virus Coding Sequences

pigs in a farm
pigs in a farm

It appears that the common ancestor of the modern hepatitis E virus (HEV) strains emerged approximately 6800 years ago in the period following the domestication of pigs, and natural selection has played a major role in the evolution of the codon usage of HEV open reading frames (ORFs), according to study results published in BMC Genomics.

HEV comprises 8 genotypes with a diverse range of hosts including humans, pigs, deer, wild boar, and camels with a wide geographic distribution, making hepatitis E a global public health concern. Given the continuously growing number of reported HEV genome sequences, researchers performed a comprehensive analysis of the composition and codon usage features of HEV full genomes reported between 1982 and 2017, followed by Bayesian phylogenetics analysis to retrace the evolutionary history of HEV.

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They found that the common ancestor of the modern HEV strains emerged approximately 6800 years ago, in the period following the domestication of pigs and the intensification of agriculture. Under these domestication conditions, adaptive changes occurred in the common ancestor allowing the emergence of zoonotic and human HEV strains.

Although mutation pressure effects cannot be excluded in the evolutionary process, natural selection was identified as the major factor influencing the codon usage patterns in HEV ORFs, which may explain or could be explained by the wide range of HEV hosts. Of note, all of these factors together permitted the occurrence of significant adaptation changes in the ORF1 of genotype 1 to humans, making the ORF1 an evolutionary indicator of HEV host speciation.

The investigators concluded that, “further history or fossil record findings as well as the isolation of new HEV strains from more hosts are need[ed] for the determination of the accurate evolutionary history of HEV.”


Baha S, Behloul N, Liu Z, Wei W, Shi R, Meng J. Comprehensive analysis of genetic and evolutionary features of the hepatitis E virus. BMC Genomics. 2019;20(1):790.