A recent origin of Orf3a from M protein across the coronavirus lineage arising by sharp divergence.

Computational and Structural Biotechnology Journal
Christos A Ouzounis

Abstract

The genome of SARS-CoV-2, the coronavirus responsible for the Covid-19 pandemic, encodes a number of accessory genes. The longest accessory gene, Orf3a, plays important roles in the virus lifecycle indicated by experimental findings, known polymorphisms, its evolutionary trajectory and a distinct three-dimensional fold. Here we show that supervised, sensitive database searches with Orf3a detect weak, yet significant and highly specific similarities to the M proteins of coronaviruses. The similarity profiles can be used to derive low-resolution three-dimensional models for M proteins based on Orf3a as a structural template. The models also explain the emergence of Orf3a from M proteins and suggest a recent origin across the coronavirus lineage, enunciated by its restricted phylogenetic distribution. This study provides evidence for the common origin of M and Orf3a families and proposes for the first time a working model for the structure of the universally distributed M proteins in coronaviruses, consistent with the properties of both protein families.

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Citations

Apr 15, 2021·Expert Review of Molecular Diagnostics·Davide ZellaMassimo Ciccozzi

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Methods Mentioned

BETA
phylogenetic profiles

Software Mentioned

MView
Pro
PSI
FastTree
MicroReact
QMEAN
MAFFT
DALI
Origami
AlignmentViewer

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