Identification of Novel Missense Mutations in a Large Number of Recent SARS-CoV-2 Genome Sequences

Abstract

SARS-CoV-2 infection has spread to over 200 countries since it was first reported in December of 2019. Significant country-specific variations in infection and mortality rate have been noted. We performed a sequence analysis of 474 SARS-CoV-2 genomes submitted to GenBank up to April 11 and identified 5 recently emerged mutations in many the isolates (up to 40%). This finding was verified on a larger scale using the GISAID database with 8,008 SARS-CoV-2 sequences. Our analysis highlights 5 frequent new mutations that have emerged since late February 2020. These mutations are: one each missense (non-synonymous) mutation in orf1ab (C1059T), orf3 (G25563T) and orf8 (C27964T), one in 5’UTR (C241T), one in a non-coding region (G29553A). The final mutation (G29553A) was found to be almost exclusive to the US isolates. The first 3 mutations are non-synonymous, leading to amino acid substitutions in the viral protein sequence. Except for C241T, all the novel mutations identified are absent in the isolates from Italy and Spain. Although the clinical significance of these mutations is currently unclear, the findings lay the foundation for further study into the impact of SARS-CoV-2 mutations on disease incidence, severity, and host immune response. In addition, it may also provide insights into vaccine development and serological response detection for the virus.

Analysis of SARS-CoV-2 Genomes from Southern California Reveals Community Transmission Pathways in the Early Stage of the US COVID-19 Pandemic

“…Consistent with other studies, the combination of the four variants(C241T, C3037T, C14408T, A23403G) co-evolving and tracking together has been seen in other populations tracking in European isolates 18 . From our variant analysis, two of our highly mutated sites, G25563T (ORF3a) and C1059T (nsp2) have been reported exclusively in US isolated sequences collected since March 2020 25 , a timeline which corresponds to this study’s sample collection date. Moreover, these variants were found to be closely associated within a cluster containing mainly SARS-CoV-2 genomes from New York State, suggesting that these genomes were introduced from a strain that emerged from the US East Coast population.…”

Analysis of Genomic Characteristics and Transmission Routes of Patients With Confirmed SARS-CoV-2 in Southern California During the Early Stage of the US COVID-19 Pandemic

“…4 Assessing core genomic features across all global populations can be used for comparative analysis to identify features unique to SARS-CoV-2 as well as assist in epidemiologic and public health endeavors. 2,[5][6][7][8][9][10][11][12][13][14][15] SARS-CoV-2 is a coronavirus with a 29 903-base pair (bp) single-stranded RNA genome 16 containing 14 open reading frames and 27 estimated proteins. 17 Viral genome annotation can assess the conserved wild-type sequence across all patients with COVID-19.…”

Global analysis of more than 50,000 SARS-CoV-2 genomes reveals epistasis between eight viral genes

“…We find that eight predictions stand out between pairs of polymorphic sites located in genes nsp2 and ORF3a, in genes nsp4 and ORF8, and between genes nsp2, nsp6, nsp12, nsp13, nsp14 and ORF3a. Most of these sites have been documented in the literature when it comes to single-locus variations ( 22 – 27 ). The nsp4–ORF8 pair was additionally found to be strongly correlated, in an early study ( 28 ).…”