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Classic human astroviruses (HAstV) are major global viral agents for gastroenteritis, but the molecular characteristics of classic HAstVs are not well understood. Here, we presented the molecular evolution of all classic HAstV serotypes by the analysis of the capsid protein sequences. Our results show that classic HAstVs can be divided into four groups with the most recent common ancestor (TMRCA) of 749. The overall evolutionary rate of classic HAstVs on the capsid gene was 4.509×10 -4 substitutions/site/year, and most of the serotypes present a clock-like evolution with an amino acid accumulation of mutations over time. The mean effective population size of classic HAstVs is in a downward trend, and some positive and more than 500 negative selection sites were determined. Taken together, these results reveal that classic HAstVs evolve at the intra-serotype level with high genetic heterogeneity and are driven by strong purifying selection. Long-term surveillance of classic HAstVs are needed to enrich the genomic data for further analysis.

Molecular Evolution of Classic Human Astrovirus, as Revealed by the Analysis of the Capsid Protein Gene