Human pathogenic RNA viruses establish non-competing lineages by occupying independent niches

Mutz, Pascal; Rochman, Nash D.; Wolf, Yuri I.; Faure, Guilhem; Zhang, Feng; Koonin, Eugene V.

doi:10.1101/2021.12.10.472150

Cited by 3 publications

(5 citation statements)

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“…S6 ). Additionally, it has been shown that many human pathogenic RNA viruses exhibit heterogeneous coalescence times as a consequence of variation in selection over time ( 71 ). We have controlled for this by separately inferring pool recombination rates for individual SL-CoV sequence clusters or cluster pairs ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Correlated substitutions reveal SARS-like coronaviruses recombine frequently with a diverse set of structured gene pools

Steinberg

Silander

Kussell

2023

Proc. Natl. Acad. Sci. U.S.A.

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Quantifying SARS-like coronavirus (SL-CoV) evolution is critical to understanding the origins of SARS-CoV-2 and the molecular processes that could underlie future epidemic viruses. While genomic analyses suggest recombination was a factor in the emergence of SARS-CoV-2, few studies have quantified recombination rates among SL-CoVs. Here, we infer recombination rates of SL-CoVs from correlated substitutions in sequencing data using a coalescent model with recombination. Our computationally-efficient, non-phylogenetic method infers recombination parameters of both sampled sequences and the unsampled gene pools with which they recombine. We apply this approach to infer recombination parameters for a range of positive-sense RNA viruses. We then analyze a set of 191 SL-CoV sequences (including SARS-CoV-2) and find that ORF1ab and S genes frequently undergo recombination. We identify which SL-CoV sequence clusters have recombined with shared gene pools, and show that these pools have distinct structures and high recombination rates, with multiple recombination events occurring per synonymous substitution. We find that individual genes have recombined with different viral reservoirs. By decoupling contributions from mutation and recombination, we recover the phylogeny of non-recombined portions for many of these SL-CoVs, including the position of SARS-CoV-2 in this clonal phylogeny. Lastly, by analyzing >400,000 SARS-CoV-2 whole genome sequences, we show current diversity levels are insufficient to infer the within-population recombination rate of the virus since the pandemic began. Our work offers new methods for inferring recombination rates in RNA viruses with implications for understanding recombination in SARS-CoV-2 evolution and the structure of clonal relationships and gene pools shaping its origins.

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Section: Discussionmentioning

confidence: 99%

Correlated substitutions reveal SARS-like coronaviruses recombine frequently with a diverse set of structured gene pools

Steinberg

Silander

Kussell

2023

Proc. Natl. Acad. Sci. U.S.A.

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“…While related, these events are distinct from those features that emerge as a result of rapid adaptation following a host switch, and elucidating the requirements (conserved or speciesspecific) for human transmission will require commensurate sequencing efforts for non-human species (Box 1, Question 5). Sequences from intermediate hosts or early human infections are missing for all but one (H1N1) of the epidemic viruses discussed here (See Fig 1), and varying selection pressures over time (Mutz et al, 2022) or even strong, constant purifying selection, characteristic of viral evolution (Wertheim & Kosakovsky Pond, 2011), make it impossible to uncover many adaptations to human hosts from the comparative genomics of human viruses alone.…”

Section: Adaptations Beyond Cell Entrymentioning

confidence: 99%

“…Large populations, short generation times, and high mutation rates enable viruses to undergo extremely rapid, adaptive molecular evolution (Drake & Holland, 1999; Sanjuán, 2012). Even at the species level, variations in selective pressures over time (Mutz et al , 2022) and, in particular, the overwhelming effect of purifying selection (Wertheim & Kosakovsky Pond, 2011) can obfuscate evolutionary histories.…”

Section: Introductionmentioning

confidence: 99%

“…Unprecedented genomic sequencing efforts enabled the rapid identification and real‐time surveillance of the molecular evolution of SARS‐CoV‐2, with public data sharing facilitated by GenBank (Benson et al , 2012), the China National Center for Bioinformation (CNCB) (Zhao et al , 2020), and Gisaid (Elbe & Buckland‐Merrett, 2017). These efforts resulted in more sequences obtained for SARS‐CoV‐2 than any other virus by several orders of magnitude at the time of writing (Mutz et al , 2022). The SARS‐CoV‐2 genome is closely related to a bat coronavirus RaTG13, with a sequence identity of more than 96%.…”

Section: Introductionmentioning

confidence: 99%

“…These epidemiological factors are rapidly changing in many parts of the world as a result of modernization, globalization, and climate change. Phylodynamic analysis suggests that most human viruses form stable, noncompeting epidemiological niches marked by largely neutral evolution (Mutz et al , 2022) similar to the apparent landscape of Zika within Africa. The export of strains that have neutrally evolved within a small, stable epidemiological niche into a much larger community of susceptible hosts not only increases the epidemic potential in the short term but also introduces new selective pressures as a result of interstrain competition which can lead to more robust human adaptation.…”

Section: Introductionmentioning

confidence: 99%

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In 1977, the world witnessed both the eradication of smallpox and the beginning of the modern age of genomics. Over the following half-century, 7 epidemic viruses of international concern galvanized virologists across the globe and led to increasingly extensive virus genome sequencing. These sequencing efforts exerted over periods of rapid adaptation of viruses to new hosts, in particular, humans provide insight into the molecular mechanisms underpinning virus evolution. Investment in virus genome sequencing was dramatically increased by the unprecedented support for phylogenomic analyses during the COVID-19 pandemic. In this review, we attempt to piece together comprehensive molecular histories of the adaptation of variola virus, HIV-1 M, SARS, H1N1-SIV, MERS, Ebola, Zika, and SARS-CoV-2 to the human host. Disruption of genes involved in virus-host interaction in animal hosts, recombination including genome segment reassortment, and adaptive mutations leading to amino acid replacements in virus proteins involved in host receptor binding and membrane fusion are identified as the key factors in the evolution of epidemic viruses.

show abstract

Correlated substitutions reveal SARS-like coronaviruses recombine frequently with a diverse set of structured gene pools

Steinberg

Silander

Kussell

2022

Preprint

View full text Add to dashboard Cite

Quantifying SARS-like coronavirus (SL-CoV) evolution is critical to understanding the origins of SARS-CoV-2 and the molecular processes that could underlie future epidemic viruses. While genomic evidence implicates recombination as a factor in the emergence of SARS-CoV-2, few studies have quantified recombination rates among SL-CoVs. Here, we infer recombination rates of SL-CoVs from correlated substitutions in sequencing data using a coalescent model with recombination. Our computationally-efficient, non-phylogenetic method infers recombination parameters of both sampled sequences and the unsampled gene pools with which they recombine. We apply this approach to infer recombination parameters for a range of positive-sense RNA viruses. We then analyze a set of 191 SL-CoV sequences (including SARS-CoV-2) and find that ORF1ab and S genes frequently undergo recombination. We identify which SL-CoV sequence clusters have recombined with shared gene pools, and show that these pools have distinct structures and high recombination rates, with multiple recombination events occurring per synonymous substitution. We find that individual genes have recombined with different viral reservoirs. By decoupling contributions from mutation and recombination, we recover the phylogeny of non-recombined portions for many of these SL-CoVs, including the position of SARS-CoV-2 in this clonal phylogeny. Lastly, by analyzing 444,145 SARS-CoV-2 whole genome sequences, we show current diversity levels are insufficient to infer the within-population recombination rate of the virus since the pandemic began. Our work offers new methods for inferring recombination rates in RNA viruses with implications for understanding recombination in SARS-CoV-2 evolution and the structure of clonal relationships and gene pools shaping its origins.

show abstract

Human pathogenic RNA viruses establish non-competing lineages by occupying independent niches

Cited by 3 publications

References 72 publications

Correlated substitutions reveal SARS-like coronaviruses recombine frequently with a diverse set of structured gene pools

Correlated substitutions reveal SARS-like coronaviruses recombine frequently with a diverse set of structured gene pools

Molecular adaptations during viral epidemics

Correlated substitutions reveal SARS-like coronaviruses recombine frequently with a diverse set of structured gene pools

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