Identification of novel missense mutations in a large number of recent SARS-CoV-2 genome sequences

Abstract

Background. 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. Although country-specific differences in public health response have had a large impact on infection rate control, it is currently unclear as to whether evolution of the virus itself has also contributed to variations in infection and mortality rate. Previous studies on SARS-CoV-2 mutations were based on the analysis of ~ 160 SARS-CoV-2 sequences available until mid-February 2020. 2, 3, 4, 5 By mid-April, > 550 SARS-CoV-2 sequences had been deposited in GenBank, and over 8,200 in the GISAID database. Methods. We performed a sequence analysis on 474 SARS-CoV-2 genomes submitted to GenBank up to April 11, 2020 by multiple alignment using Map to a Reference Assembly and Variants/SNP identification. The results were verified on a larger scale, 8,126 hCoV-19 (SARS-CoV-2) sequences from GISAID database. Results. We identified 5 recently emerged mutations in many isolates (up to 40%). 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 in the SARS-CoV-2 genomes deposited in GenBank and GISAID. Conclusion. The results of current study indicate that new mutations are emerging as COVID-19 pandemic are spreading to different countries and that geography specific mutants exist. The findings of current study lay the foundation for further investigation 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 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

“…In this case series, consistent with other studies, the combination of the 4 variants (ie, C241T, C3037T, C14408T, and A23403G) coevolving together has been seen in other tracked populations in European isolates . From our variant analysis, 2 of our highly altered sites, G25563T(ORF3a) and C1059T(nsp2), have been reported exclusively in US isolated sequences collected since March 2020, a timeline that corresponds to this study’s sample collection date. These variants were found to be closely associated within a cluster containing mainly SARS-CoV-2 genomes from New York, suggesting that these genomes were introduced from a strain that emerged from the US East Coast population.…”

“…The SARS-CoV-2 genome sequences deposited in public databases are pivotal resources in understanding its virulence and for guiding approaches to therapeutics and vaccines . 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 …”

Unsupervised clustering analysis of SARS-Cov-2 population structure reveals six major subtypes at early stage across the world

“…The strains with this trinucleotide mutation were all in cluster F in the K-means clustering results. In addition to the trinucleotide mutation, many of the extracted substitutions were reported to be related to the evolution of SARS-CoV-2(38)(39)(40)(41). Tang et al(42) defined "L" type (defined as "L" type because T28,144 is in the codon of Leucine) and "S" type (defined as "S" type because C28,144 is in the codon of Serine) of SARS-CoV-2 through two genetically linked mutations C8782T and T28144C.…”

Adaptive trends of sequence compositional complexity over pandemic time in the SARS-CoV-2 coronavirus

“…In the brief time since the COVID-19 pandemic appeared, and despite viral genomic proofreading mechanism, recombinations have accumulated 19 over multiple rounds of mutations, many of which have increased viral fitness 8,[20][21][22] . Synonymous and non-synonymous mutations [23][24][25] , as well as mismatches and deletions in translated and untranslated regions 18 have been tracked. Of particular interest are those non-synonymous mutations provoking epitope loss and antibody escaping found mainly in evolved variants isolated from Europe and the Americas, which have critical implications for SARS-CoV-2 transmission, pathogenesis, and immune interventions 26 .…”

“…Noteworthy, RNA viruses can also accumulate high genetic variation during individual outbreaks (Pybus, Tatem, and Lemey 2015), showing mutation and evolutionary rates up to a million times higher than those of their hosts (Islam et al 2020). Synonymous and non-synonymous mutations (Banerjee et al 2020; Cai, Cai, and Li 2020), as well as mismatches and deletions in translated and untranslated regions (Islam et al 2020; Young et al 2020) have been tracked in the SARs-CoV-2 genome sequence.…”