1. Quasi-species nature and differential gene expression of severe acute respiratory syndrome coronavirus 2 and phylogenetic analysis of a novel Iranian strain
- Author
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Mohammad Hadi Eskandari, Abozar Ghorbani, Jonathan R. Peters, Thomas P Karbanowicz, Samira Samarfard, Keramatollah Izadpanah, Alireza Afsharifar, and Amin Ramezani
- Subjects
0301 basic medicine ,Microbiology (medical) ,Gene Expression Regulation, Viral ,viruses ,030106 microbiology ,Population ,Inter-host ,Single-nucleotide polymorphism ,Biology ,Iran ,medicine.disease_cause ,Virus Replication ,Genome ,Microbiology ,Polymorphism, Single Nucleotide ,DNA sequencing ,Virus ,03 medical and health sciences ,Phylogenetic ,Viral Proteins ,Genetic variation ,medicine ,Genetics ,Humans ,education ,skin and connective tissue diseases ,Nucleocapsid ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Phylogeny ,Coronavirus ,education.field_of_study ,SARS-CoV-2 ,Sequence Analysis, RNA ,Gene Expression Profiling ,COVID-19 ,High-Throughput Nucleotide Sequencing ,Open reading frame ,Single nucleotide polymorphism ,body regions ,Quasispecies ,030104 developmental biology ,Infectious Diseases ,Pharynx ,Research Paper - Abstract
A novel coronavirus related to severe acute respiratory syndrome virus, (SARS-CoV-2) is the causal agent of the COVID-19 pandemic. Despite the genetic mutations across the SARS-CoV-2 genome being recently investigated, its transcriptomic genetic polymorphisms at inter-host level and the viral gene expression level based on each Open Reading Frame (ORF) remains unclear. Using available High Throughput Sequencing (HTS) data and based on SARS-CoV-2 infected human transcriptomic data, this study presents a high-resolution map of SARS-CoV-2 single nucleotide polymorphism (SNP) hotspots in a viral population at inter-host level. Four throat swab samples from COVID-19 infected patients were pooled, with RNA-Seq read retrieved from SRA NCBI to detect 21 SNPs and a replacement across the SARS-CoV-2 genomic population. Twenty-two RNA modification sites on viral transcripts were identified that may cause inter-host genetic diversity of this virus. In addition, the canonical genomic RNAs of N ORF showed higher expression in transcriptomic data and reverse transcriptase quantitative PCR compared to other SARS-CoV-2 ORFs, indicating the importance of this ORF in virus replication or other major functions in virus cycle. Phylogenetic and ancestral sequence analyses based on the entire genome revealed that SARS-CoV-2 is possibly derived from a recombination event between SARS-CoV and Bat SARS-like CoV. Ancestor analysis of the isolates from different locations including Iran suggest shared Chinese ancestry. These results propose the importance of potential inter-host level genetic variations to the evolution of SARS-COV-2, and the formation of viral quasi-species. The RNA modifications discovered in this study may cause amino acid sequence changes in polyprotein, spike protein, product of ORF8 and nucleocapsid (N) protein, suggesting further insights to understanding the functional impacts of mutations in the life cycle and pathogenicity of SARS-CoV-2., Highlights • RdRp, S proteins, ORF8, and nucleoprotein (N) of SARS-CoV-2 have undergone mutations at the inter-host level. • SARS-CoV-2 N gene is expressed abundantly during infection comparing to the 5′ terminal genes. • Single nucleotide polymorphisms in SARS-CoV-2 at Inter-host level cause amino acid changes in the virus genome. • Ancestor analysis of the SARS-CoV-2 isolates from different locations reveals shared Chinese ancestry.
- Published
- 2020