Genetic drift of human coronavirus OC43 spike gene during adaptive evolution

Abstract

Coronaviruses (CoVs) continuously threaten human health. However, to date, the evolutionary mechanisms that govern CoV strain persistence in human populations have not been fully understood. In this study, we characterized the evolution of the major antigen-spike (S) gene in the most prevalent human coronavirus (HCoV) OC43 using phylogenetic and phylodynamic analysis. Among the five known HCoV-OC43 genotypes (A to E), higher substitution rates and dN/dS values as well as more positive selection sites were detected in the S gene of genotype D, corresponding to the most dominant HCoV epidemic in recent years. Further analysis showed that the majority of substitutions were located in the S1 subunit. Among them, seven positive selection sites were chronologically traced in the temporal evolution routes of genotype D, and six were located around the critical sugar binding region in the N-terminal domain (NTD) of S protein, an important sugar binding domain of CoV. These findings suggest that the genetic drift of the S gene may play an important role in genotype persistence in human populations, providing insights into the mechanisms of HCoV-OC43 adaptive evolution.

Figure 1. Relative genetic diversity dynamics of OC43 and each genotype.

Population size was determined using sequences of 96 OC43 S genes obtained from 2003 to 2012. The median estimates (g) are represented by the black lines and 95% high posterior densities are shown in the color regions.

Figure 2. Molecular clock analysis of OC43 genotype D.

The complete S gene sequences sampled from 2007 to 2012 were used to reconstruct the phylogeny. The calculated positive selection sites in each node are drawn on the MCC tree.