Definition: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
Input: 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. Coronaviruses (CoVs) are widely found in humans as well as in mammalian and avian species, causing asymptomatic infections or respiratory tract disorders, and gastroenteritis of varying severity 1 . CoVs belong to the genus Coronavirus of family Coronaviridae, and are classified into four genera, Alphacoronavirus (α -CoV), Betacoronavirus (ß-CoV), Gammacoronavirus, and Deltacoronavirus based on phylogenetics and serology 1 . To date, α -CoV [including human CoV (HCoV)-229E and NL63] and ß-CoV [including HCoV-OC43, HKU1, Severe Acute Respiratory Syndrome CoV (SARS-CoV) and Middle East Respiratory Syndrome CoV (MERS-CoV)] are known to infect human beings 1 . Interspecies transmission is a common phenomenon for CoVs that may be responsible for generation of new CoV epidemics during viral evolution 2-5 . For instance, the feline CoV (FCoV) type II, a member of α -CoV, might be generated by a double recombination between FCoV type I and canine CoV 4 . Interestingly, porcine hemagglutinating encephalomyelitis virus, bovine CoV (BCoV) and HCoV-OC43 of ß-CoV are thought to have evolved from the same common ancestor 5 . During evolution, high frequencies of homologous RNA recombination and gene mutations are considered the main forces that push CoVs to adapt to specific hosts. Such events can lead to emergence of new strains or genotypes within a certain species, and even to new species, causing epidemic or zoonotic outbreaks that continuously threaten human health 2,3 . This phenomenon is exemplified by the recent emergence of SARS-CoV and MERS-CoV 6,7 . However, the detailed evolutionary mechanism of interspecies transmission and the persistence of CoVs in specific hosts have yet to be fully elucidated.

Genetic drift of human coronavirus OC43 spike gene during adaptive evolution OPEN