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

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Summary

Introduction

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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