Mol Biol Evol . Stepwise evolution and exceptional conservation of ORF1a/b overlap in coronaviruses

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Mol Biol Evol


. 2021 Sep 10;msab265.
doi: 10.1093/molbev/msab265. Online ahead of print.
Stepwise evolution and exceptional conservation of ORF1a/b overlap in coronaviruses


Han Mei ¹ , Sergei Kosakovsky Pond ² , Anton Nekrutenko ¹



Affiliations

• PMID: 34505896
• DOI: 10.1093/molbev/msab265

Abstract

The programmed frameshift element (PFE) rerouting translation from ORF1a to ORF1b is essential for propagation of coronaviruses. The combination of genomic features that make up PFE-the overlap between the two reading frames, a slippery sequence, as well as an ensemble of complex secondary structure elements-places severe constraints on this region as most possible nucleotide substitution may disrupt one or more of these elements. The vast amount of SARS-CoV-2 sequencing data generated within the past year provides an opportunity to assess evolutionary dynamics of PFE in great detail. Here we performed a comparative analysis of all available coronaviral genomic data available to date. We show that the overlap between ORF1a and ORF1b evolved as a set of discrete 7, 16, 22, 25, and 31 nucleotide stretches with a well defined phylogenetic specificity. We further examined sequencing data from over 1,500,000 complete genomes and 55,000 raw read datasets to demonstrate exceptional conservation and detect signatures of selection within the PFE region.