BACKGROUND Evolutionary changes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include indels in non-structural, structural, and accessory open reading frames (ORFs) or genes. OBJECTIVES We track indels in accessory ORFs to infer evolutionary gene patterns and epidemiological links between outbreaks. METHODS Genomes from Coronavirus disease 2019 (COVID-19) case-patients were Illumina sequenced using ARTIC_V3. The assembled genomes were analysed to detect substitutions and indels. FINDINGS We reported the emergence and spread of a unique 4-nucleotide deletion in the accessory ORF6, an interesting gene with immune modulation activity. The deletion in ORF6 removes one repeat unit of a two 4-nucleotide repeat, which shows that directly repeated sequences in the SARS-CoV-2 genome are associated with indels, even outside the context of extended repeat regions. The 4-nucleotide deletion produces a frameshifting change that results in a protein with two inserted amino acids, increasing the coding information of this accessory ORF. Epidemiological and genomic data indicate that the deletion variant has a single common ancestor and was initially detected in a health care outbreak and later in other COVID-19 cases, establishing a transmission cluster in the Uruguayan population. MAIN CONCLUSIONS Our findings provide evidence for the origin and spread of deletion variants and emphasise indels’ importance in epidemiological studies, including differentiating consecutive outbreaks occurring in the same health facility.
【저자키워드】 coronavirus, genetics, indels, accessory gene, repetitive sequence, 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, Coronavirus disease 2019, coronavirus, Health care, Genome, Transmission, severe acute respiratory syndrome Coronavirus, immune modulation, Spread, Protein, Outbreaks, Health, outbreak, SARS-CoV-2 genome, substitutions, amino acids, Cluster, Deletion, ORF6, indels, respiratory, information, Illumina, Care, ORFs, Evidence, Open reading frame, COVID-19 cases, open reading frames, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, epidemiological studies, genomic data, sequence, coding, epidemiological links, Substitution, INDEL, epidemiological link, Deletion variants, deletion variant, nucleotide deletion, repeat unit, Genes, regions, repeated, detect, sequenced, include, reported, analysed, ORF, changes in, unique, the SARS-CoV-2 genome, 【제목키워드】 SARS-CoV-2, Cluster, COVID-19 case,