Population Genetics
The most recent common ancestor of Hepatitis E evolved between 536 and 1344 years ago. It diverged into two clades - an anthropotropic and an enzootic form - which subsequently evolved into genotypes 1 and 2 and genotypes 3 and 4 respectively. The divergence dates for the various genotypes are as follows: Genotypes 1/2 367 – 656 years ago; Genotypes 3/4 417 – 679 years ago. For the most recent common acestor of the various viruses themselves: Genotype 1 between 87 and 199 years ago; Genotype 3 between 265 and 342 years ago; and Genotype 4 between 131 and 266 years ago. The anthropotropic strains (genotype 1 and 2) have evolved more recently than the others suggesting that this virus was originally a zooenosis.
The use of an avian strain confirmed the proposed topology of the genotypes 1-4 and suggested that the genus may have evolved 1.36 million years ago (range 0.23 million years ago to 2.6 million years ago). The use of a rat sequence also confirmed this topology and estimated date of divergence from the swine/human strains was 7.44×104 years ago (range 2.1×104 to 1.4×105 years ago) Since this date is approximately coincident with the advent of agriculture it may be that this virus originally infected rats and subsequently spread to pigs and then to humans. Additional work is required to support or refute this possibility as very few sequences have been isolated from species other than humans and suids.
Genotypes 1,3 and 4 all increased their effective population sizes in the 20th century. The population size of genotype 1 increaded noticeably in the last 30–35 years. Genotypes 3 and 4 population sizes began to increase in the late 19th century up to 1940-1945. Genotype 3 underwent a subsequent increase in population size until the 1960s. Since 1990 both genotypes' population sizes have been reduced back to levels last seen in the 19th century.
The overall mutation rate for the genome has been estimated at ~1.4 x 10−3 substitutions/site/year.
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