Abstract
Identification of the full complement of genes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a crucial step towards gaining a fuller understanding of its molecular biology. However, short and/or overlapping genes can be difficult to detect using conventional computational approaches, whereas high-throughput experimental approaches – such as ribosome profiling – cannot distinguish translation of functional peptides from regulatory translation or translational noise. By studying regions showing enhanced conservation at synonymous sites in alignments of SARS-CoV-2 and related viruses (subgenus Sarbecovirus) and correlating the results with the conserved presence of an open reading frame (ORF) and a plausible translation mechanism, a putative new gene – ORF3c – was identified. ORF3c overlaps ORF3a in an alternative reading frame. A recently published ribosome profiling study confirmed that ORF3c is indeed translated during infection. ORF3c is conserved across the subgenus Sarbecovirus, and encodes a 40–41 amino acid predicted transmembrane protein.
Highlights
Identification of the full complement of genes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a crucial step towards gaining a fuller understanding of its molecular biology
The 5′ two-thirds of the genome contain two long open reading frames (ORFs), ORF1a and ORF1b, which are translated from the viral genomic RNA
ORFs 1a and 1b encode the polyproteins pp1a and pp1ab, where translation of pp1ab depends on a proportion of ribosomes making a programmed −1 nt ribosomal frameshift near the end of ORF1a to enter ORF1b
Summary
Identification of the full complement of genes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a crucial step towards gaining a fuller understanding of its molecular biology. The 5′ two-thirds of the genome contain two long open reading frames (ORFs), ORF1a and ORF1b, which are translated from the viral genomic RNA (gRNA). The 3′ third of the genome contains a number of ORFs that encode the viral structural and accessory proteins.
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