Host-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process

The capacity of RNA viruses to adapt to new hosts and rapidly escape the host immune system is largely attributable to de novo genetic diversity that emerges through mutations in RNA. Although the molecular spectrum of de novo mutations—the relative rates at which various base substitutions occur—ar...

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Autores principales:	Ke-Jia Shan, Changshuo Wei, Yu Wang, Qing Huan, Wenfeng Qian
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	SARS-CoV-2 molecular spectrum de novo mutations mutational signature evolutionary origin mRNA mutation Science (General) Q1-390
Acceso en línea:	https://doaj.org/article/a0297591f49e4f3aa2ba6d3b93d4901b
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spelling	oai:doaj.org-article:a0297591f49e4f3aa2ba6d3b93d4901b2021-11-28T04:38:58ZHost-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process2666-675810.1016/j.xinn.2021.100159https://doaj.org/article/a0297591f49e4f3aa2ba6d3b93d4901b2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666675821000849https://doaj.org/toc/2666-6758The capacity of RNA viruses to adapt to new hosts and rapidly escape the host immune system is largely attributable to de novo genetic diversity that emerges through mutations in RNA. Although the molecular spectrum of de novo mutations—the relative rates at which various base substitutions occur—are widely recognized as informative toward understanding the evolution of a viral genome, little attention has been paid to the possibility of using molecular spectra to infer the host origins of a virus. Here, we characterize the molecular spectrum of de novo mutations for SARS-CoV-2 from transcriptomic data obtained from virus-infected cell lines, enabled by the use of sporadic junctions formed during discontinuous transcription as molecular barcodes. We find that de novo mutations are generated in a replication-independent manner, typically on the genomic strand, and highly dependent on mutagenic mechanisms specific to the host cellular environment. De novo mutations will then strongly influence the types of base substitutions accumulated during SARS-CoV-2 evolution, in an asymmetric manner favoring specific mutation types. Consequently, similarities between the mutation spectra of SARS-CoV-2 and the bat coronavirus RaTG13, which have accumulated since their divergence strongly suggest that SARS-CoV-2 evolved in a host cellular environment highly similar to that of bats before its zoonotic transfer into humans. Collectively, our findings provide data-driven support for the natural origin of SARS-CoV-2. Public summary: • The asymmetric de novo mutations in SARS-CoV-2 are induced by mutagenic mechanisms in the host cellular environment • De novo mutations determine the molecular spectrum of accumulated mutations during SARS-CoV-2 evolution • Molecular spectra of accumulated mutations in betacoronaviruses cluster according to the host species instead of the phylogenetic relationship • The mutations accumulated in SARS-CoV-2 prior to its transmission to humans are consistent with an evolutionary process in a bat hostKe-Jia ShanChangshuo WeiYu WangQing HuanWenfeng QianElsevierarticleSARS-CoV-2molecular spectrumde novo mutationsmutational signatureevolutionary originmRNA mutationScience (General)Q1-390ENThe Innovation, Vol 2, Iss 4, Pp 100159- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 molecular spectrum de novo mutations mutational signature evolutionary origin mRNA mutation Science (General) Q1-390
spellingShingle	SARS-CoV-2 molecular spectrum de novo mutations mutational signature evolutionary origin mRNA mutation Science (General) Q1-390 Ke-Jia Shan Changshuo Wei Yu Wang Qing Huan Wenfeng Qian Host-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process
description	The capacity of RNA viruses to adapt to new hosts and rapidly escape the host immune system is largely attributable to de novo genetic diversity that emerges through mutations in RNA. Although the molecular spectrum of de novo mutations—the relative rates at which various base substitutions occur—are widely recognized as informative toward understanding the evolution of a viral genome, little attention has been paid to the possibility of using molecular spectra to infer the host origins of a virus. Here, we characterize the molecular spectrum of de novo mutations for SARS-CoV-2 from transcriptomic data obtained from virus-infected cell lines, enabled by the use of sporadic junctions formed during discontinuous transcription as molecular barcodes. We find that de novo mutations are generated in a replication-independent manner, typically on the genomic strand, and highly dependent on mutagenic mechanisms specific to the host cellular environment. De novo mutations will then strongly influence the types of base substitutions accumulated during SARS-CoV-2 evolution, in an asymmetric manner favoring specific mutation types. Consequently, similarities between the mutation spectra of SARS-CoV-2 and the bat coronavirus RaTG13, which have accumulated since their divergence strongly suggest that SARS-CoV-2 evolved in a host cellular environment highly similar to that of bats before its zoonotic transfer into humans. Collectively, our findings provide data-driven support for the natural origin of SARS-CoV-2. Public summary: • The asymmetric de novo mutations in SARS-CoV-2 are induced by mutagenic mechanisms in the host cellular environment • De novo mutations determine the molecular spectrum of accumulated mutations during SARS-CoV-2 evolution • Molecular spectra of accumulated mutations in betacoronaviruses cluster according to the host species instead of the phylogenetic relationship • The mutations accumulated in SARS-CoV-2 prior to its transmission to humans are consistent with an evolutionary process in a bat host
format	article
author	Ke-Jia Shan Changshuo Wei Yu Wang Qing Huan Wenfeng Qian
author_facet	Ke-Jia Shan Changshuo Wei Yu Wang Qing Huan Wenfeng Qian
author_sort	Ke-Jia Shan
title	Host-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process
title_short	Host-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process
title_full	Host-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process
title_fullStr	Host-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process
title_full_unstemmed	Host-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process
title_sort	host-specific asymmetric accumulation of mutation types reveals that the origin of sars-cov-2 is consistent with a natural process
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/a0297591f49e4f3aa2ba6d3b93d4901b
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Host-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process

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