Evolutionary trajectory of SARS-CoV-2 and emerging variants

Abstract

The emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more recently, the independent evolution of multiple SARS-CoV-2 variants has generated renewed interest in virus evolution and cross-species transmission. While all known human coronaviruses (HCoVs) are speculated to have originated in animals, very little is known about their evolutionary history and factors that enable some CoVs to co-exist with humans as low pathogenic and endemic infections (HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1), while others, such as SARS-CoV, MERS-CoV and SARS-CoV-2 have evolved to cause severe disease. In this review, we highlight the origins of all known HCoVs and map positively selected for mutations within HCoV proteins to discuss the evolutionary trajectory of SARS-CoV-2. Furthermore, we discuss emerging mutations within SARS-CoV-2 and variants of concern (VOC), along with highlighting the demonstrated or speculated impact of these mutations on virus transmission, pathogenicity, and neutralization by natural or vaccine-mediated immunity.

Keywords: Coronavirus; Evolution; Mutations; SARS-CoV-2; Selection; Variants.

Fig. 1

Speculated animal origins of known human coronaviruses. HCoV species are organized chronologically (top to bottom) by their speculated dates of spill over into humans. Intermediate hosts (top to bottom) shown are alpacas, cattle, civet cats, dromedary camels, pangolins, and unknown (denoted as a question mark). Genome similarity to humans (A) indicates percentage similarity of CoV genomes detected in reservoir species with corresponding human CoV. Genome similarity to humans (B) indicates percentage similarity of CoV genomes detected in intermediate species with corresponding human CoV. Non-human CoVs that are highly pathogenic in animals, such as PEDV and SADS-CoV, are not shown here. Genomic percentage similarities were extracted from existing primary studies [, , , , , –283]

Fig. 2

Mutations identified in human coronaviruses. Red dots within the genomes correspond to specific amino acid residues that have been strongly positively selected for such that a specific mutation has become dominant in the region where it emerged [, , –, –, –, , , , , , –, , , , , –, , –, , , , –293]. Genomic regions highlighted by red bars correspond to deletions that have been selected for, while purple bars correspond to regions with significant polymorphisms within a CoV species. Beta-CoV Lineage B (Sarbecovirus) is represented within the blue shaded area, beta-CoV Lineage C (Merbecovirus) is represented within the yellow shaded area, beta-CoV Lineage A (Embecovirus) is represented within the red shaded area, and alpha-CoVs are represented within the green shaded area. Genome length in kilobases (kb) is noted on top. See Table 2 for more details