The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses

The small size of RNA virus genomes (2-to-32 kb) has been attributed to high mutation rates during replication, which is thought to lack proof-reading. This paradigm is being revisited owing to the discovery of a 3′-to-5′ exoribonuclease (ExoN) in nidoviruses, a monophyletic group of positive-strand...

Full description

Bibliographic Details
Main Authors:	Lauber, Chris, Goeman, Jelle J., Parquet, Maria del Carmen, Thi Nga, Phan, Snijder, Eric J., Morita, Kouichi, Gorbalenya, Alexander E.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715407/

id	pubmed-3715407
recordtype	oai_dc
spelling	pubmed-37154072013-07-19 The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses Lauber, Chris Goeman, Jelle J. Parquet, Maria del Carmen Thi Nga, Phan Snijder, Eric J. Morita, Kouichi Gorbalenya, Alexander E. Research Article The small size of RNA virus genomes (2-to-32 kb) has been attributed to high mutation rates during replication, which is thought to lack proof-reading. This paradigm is being revisited owing to the discovery of a 3′-to-5′ exoribonuclease (ExoN) in nidoviruses, a monophyletic group of positive-stranded RNA viruses with a conserved genome architecture. ExoN, a homolog of canonical DNA proof-reading enzymes, is exclusively encoded by nidoviruses with genomes larger than 20 kb. All other known non-segmented RNA viruses have smaller genomes. Here we use evolutionary analyses to show that the two- to three-fold expansion of the nidovirus genome was accompanied by a large number of replacements in conserved proteins at a scale comparable to that in the Tree of Life. To unravel common evolutionary patterns in such genetically diverse viruses, we established the relation between genomic regions in nidoviruses in a sequence alignment-free manner. We exploited the conservation of the genome architecture to partition each genome into five non-overlapping regions: 5′ untranslated region (UTR), open reading frame (ORF) 1a, ORF1b, 3′ORFs (encompassing the 3′-proximal ORFs), and 3′ UTR. Each region was analyzed for its contribution to genome size change under different models. The non-linear model statistically outperformed the linear one and captured >92% of data variation. Accordingly, nidovirus genomes were concluded to have reached different points on an expansion trajectory dominated by consecutive increases of ORF1b, ORF1a, and 3′ORFs. Our findings indicate a unidirectional hierarchical relation between these genome regions, which are distinguished by their expression mechanism. In contrast, these regions cooperate bi-directionally on a functional level in the virus life cycle, in which they predominantly control genome replication, genome expression, and virus dissemination, respectively. Collectively, our findings suggest that genome architecture and the associated region-specific division of labor leave a footprint on genome expansion and may limit RNA genome size. Public Library of Science 2013-07-18 /pmc/articles/PMC3715407/ /pubmed/23874204 http://dx.doi.org/10.1371/journal.ppat.1003500 Text en © 2013 Lauber et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Lauber, Chris Goeman, Jelle J. Parquet, Maria del Carmen Thi Nga, Phan Snijder, Eric J. Morita, Kouichi Gorbalenya, Alexander E.
spellingShingle	Lauber, Chris Goeman, Jelle J. Parquet, Maria del Carmen Thi Nga, Phan Snijder, Eric J. Morita, Kouichi Gorbalenya, Alexander E. The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses
author_facet	Lauber, Chris Goeman, Jelle J. Parquet, Maria del Carmen Thi Nga, Phan Snijder, Eric J. Morita, Kouichi Gorbalenya, Alexander E.
author_sort	Lauber, Chris
title	The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses
title_short	The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses
title_full	The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses
title_fullStr	The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses
title_full_unstemmed	The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses
title_sort	footprint of genome architecture in the largest genome expansion in rna viruses
description	The small size of RNA virus genomes (2-to-32 kb) has been attributed to high mutation rates during replication, which is thought to lack proof-reading. This paradigm is being revisited owing to the discovery of a 3′-to-5′ exoribonuclease (ExoN) in nidoviruses, a monophyletic group of positive-stranded RNA viruses with a conserved genome architecture. ExoN, a homolog of canonical DNA proof-reading enzymes, is exclusively encoded by nidoviruses with genomes larger than 20 kb. All other known non-segmented RNA viruses have smaller genomes. Here we use evolutionary analyses to show that the two- to three-fold expansion of the nidovirus genome was accompanied by a large number of replacements in conserved proteins at a scale comparable to that in the Tree of Life. To unravel common evolutionary patterns in such genetically diverse viruses, we established the relation between genomic regions in nidoviruses in a sequence alignment-free manner. We exploited the conservation of the genome architecture to partition each genome into five non-overlapping regions: 5′ untranslated region (UTR), open reading frame (ORF) 1a, ORF1b, 3′ORFs (encompassing the 3′-proximal ORFs), and 3′ UTR. Each region was analyzed for its contribution to genome size change under different models. The non-linear model statistically outperformed the linear one and captured >92% of data variation. Accordingly, nidovirus genomes were concluded to have reached different points on an expansion trajectory dominated by consecutive increases of ORF1b, ORF1a, and 3′ORFs. Our findings indicate a unidirectional hierarchical relation between these genome regions, which are distinguished by their expression mechanism. In contrast, these regions cooperate bi-directionally on a functional level in the virus life cycle, in which they predominantly control genome replication, genome expression, and virus dissemination, respectively. Collectively, our findings suggest that genome architecture and the associated region-specific division of labor leave a footprint on genome expansion and may limit RNA genome size.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715407/
_version_	1611995939840458752

The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses

Similar Items