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Genome Size and the Evolution of New Genes

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Related Experiment Video

Updated: Dec 7, 2025

Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization

Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization

Published on: December 23, 2020

Dynamically evolving novel overlapping gene as a factor in the SARS-CoV-2 pandemic.

Chase W Nelson^1,2, Zachary Ardern³, Tony L Goldberg^4,5

¹Biodiversity Research Center, Academia Sinica, Taipei, Taiwan.

|October 1, 2020

Summary

A novel overlapping gene, ORF3d, was discovered in SARS-CoV-2, a virus linked to COVID-19. This gene, also found in pangolin coronaviruses, has been misidentified, impacting our understanding of viral evolution and pandemic threats.

Keywords:

ORF3d SARS-CoV-2 evolutionary biology genome annotation infectious disease microbiology natural selection overlapping genes pandemic virus

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Published on: November 5, 2021

Area of Science:

Virology
Genomics
Molecular Biology

Background:

Accurate viral genome annotation is crucial for understanding novel virus emergence.
Overlapping genes (OLGs) are prevalent in viruses, often linked to pandemics, yet frequently overlooked in genomic studies.

Purpose of the Study:

To identify and characterize a novel overlapping gene, ORF3d, within the SARS-CoV-2 genome.
To investigate the evolutionary significance and potential impact of ORF3d in SARS-CoV-2 and related coronaviruses.

Main Methods:

Bioinformatic identification and characterization of the ORF3d gene in SARS-CoV-2 and related coronaviruses.
Experimental validation of ORF3d translation and protein sequence analysis.
Evolutionary analysis of ORF3d across different taxa, human hosts, and within human host populations.

Main Results:

Discovery and characterization of ORF3d, a novel OLG in SARS-CoV-2, also present in Guangxi pangolin-CoVs.
Evidence of ORF3d translation and protein expression, with significant antibody response observed in COVID-19 patients.
Demonstration of ORF3d's independent identification and its misclassification as ORF3b, causing confusion in scientific literature.

Conclusions:

ORF3d represents a significant, previously overlooked component of the SARS-CoV-2 genome.
The evolutionary analysis of ORF3d provides insights into viral adaptation and host interactions.
Highlighting the importance of OLGs in emerging viruses, likening ORF3d to other accessory genes with potential roles in viral pathogenesis.