Abstract
The ongoing coronavirus disease 2019 (COVID-19) pandemic, putatively caused by the widespread transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in significant mortality worldwide. The highly varied epidemiology of the disease both temporally and geographically has garnered much attention. The present study aimed to gain a deeper understanding of the varied geospatial disease epidemiology during the first wave of the pandemic. The highly mutable spike (S) protein, which confers fitness to SARS-CoV-2 for its survival and spread was studied using representative sequences determined from the initial phase of the pandemic. Adaptive evolution and selection pressure analysis of 311 whole-genome sequences from across the world including Asia (n=105), Europe (n=101), and the United States (n=105) was performed. A high selection pressure at position 614 of the S protein with a dN/dS (non-synonymous/synonymous substitutions per site) ratio of 124.3 for Asia and 867.9 was predicted for Europe. This positively selected site (i.e. 614) was located in the S1 domain (amino acids 14-680), which acts in binding to the angiotensin-converting co-enzyme 2 (ACE2) receptor. The US strains did not exhibit significant positive selection at position 614. In addition, 10 sites (144, 241, 255, 262, 263, 276, 439,517, 528, and 557) in domain 1 and 19 sites (692, 709, 723, 752, 862, 864, 877, 892, 939, 951, 1015, 1060, 1076, 1114, 1116, 1128, 1176, 1235 and 1240) in domain 2 of the S protein mediating viral entry into host cells, exhibited significant negative selection among European strains of (SARS-CoV-2), however, no negative selection was observed in the Asian and US groups. The D614G spike protein variant has been correlated with fatal outcomes in European population and countries including Italy, France, Belgium, and Spain. D614G variants under high selective pressure in the Asian and European strains were also observed. In addition, the presence of 29 negatively selected codon sites under low selection pressure in the European group may imply improved viral fitness compared with strains circulating in other continents. In conclusion, selective pressure on the S protein, with maximum substitution rate, may have facilitated adaptive evolution of the virus and contributed to the worldwide spread of the virus.
Highlights
The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) in December 2019 in China, with its rapid international spread, has led to a global health emergency
By February 27, 2021, >113 million cases were confirmed with >2.5 million deaths attributed to coronavirus disease 2019 (COVID-19)
The present investigation studied differences among circulating strains and the adaptive evolutionary pressures on the SARS-CoV-2 across various geographical regions during the first wave of the pandemic using sequencing data obtained between January and June 2020
Summary
The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) in December 2019 in China, with its rapid international spread, has led to a global health emergency. By February 27, 2021, >113 million cases were confirmed with >2.5 million deaths attributed to coronavirus disease 2019 (COVID-19). During the first wave of the pandemic, before June 2020, the United States (US) had borne the greatest disease burden with >. 9.4 million cases and a mortality rate of 713 deaths per million population. Europe (~4 million cases) reported the highest mortality rate (11,793 deaths/million). The difference in disease burden and outcome across geographically distinct regions could have been due to either hostrelated factors or the circulating viral strain and its adaptation to the geographical locations and the population. The present investigation studied differences among circulating strains and the adaptive evolutionary pressures on the SARS-CoV-2 across various geographical regions during the first wave of the pandemic using sequencing data obtained between January and June 2020. The S protein exhibits the greatest variability and mutational rates; it is important to characterize this protein to delineate global and region-specific evolutionary trends
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