An ancient viral epidemic involving host coronavirus interacting genes more than 20,000 years ago in East Asia
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Abstract
The current SARS-CoV-2 pandemic has emphasized the vulnerability of human populations to novel viral pressures, despite the vast array of epidemiological and biomedical tools now available. Notably, modern human genomes contain evolutionary information tracing back tens of thousands of years, which may help identify the viruses that have impacted our ancestors – pointing to which viruses have future pandemic potential. Here, we apply evolutionary analyses to human genomic datasets to recover selection events involving tens of human genes that interact with coronaviruses, including SARS-CoV-2, that likely started more than 20,000 years ago. These adaptive events were limited to the population ancestral to East Asian populations. Multiple lines of functional evidence support an ancient viral selective pressure, and East Asia is the geographical origin of several modern coronavirus epidemics. An arms race with an ancient coronavirus, or with a different virus that happened to use similar interactions as coronaviruses with human hosts, may thus have taken place in ancestral East Asian populations. By learning more about our ancient viral foes, our study highlights the promise of evolutionary information to better predict the pandemics of the future. Importantly, adaptation to ancient viral epidemics in specific human populations does not necessarily imply any difference in genetic susceptibility between different human populations, and the current evidence points toward an overwhelming impact of socioeconomic factors in the case of COVID-19.
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SciScore for 10.1101/2020.11.16.385401: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Genomes and sweeps summary statistics: To detect signatures of adaptation in various human populations, we used the 1,000 Genome Project phase 3 dataset which provides chromosome level phased data for 26 distinct human populations representing all major continental groups (1000 Genomes Project Consortium, 2015). 1000 Genomes Project Consortiumsuggested: NoneResults from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:An important limitation of our study is that some of our analyses rely upon …
SciScore for 10.1101/2020.11.16.385401: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Genomes and sweeps summary statistics: To detect signatures of adaptation in various human populations, we used the 1,000 Genome Project phase 3 dataset which provides chromosome level phased data for 26 distinct human populations representing all major continental groups (1000 Genomes Project Consortium, 2015). 1000 Genomes Project Consortiumsuggested: NoneResults from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:An important limitation of our study is that some of our analyses rely upon comparative datasets that were generated in contemporary human populations that have different ancestries than the East Asian populations where the selected CoV-VIP genes were detected. In particular, both of the eQTL and GWAS datasets come from large studies that are primarily focused on contemporary populations from Europe, and none of the five European populations in our study exhibit the selection signals observed in the genomes of East Asians. Accordingly, more direct confirmation of the causal role of 42 CoV-VIP genes in COVID-19 etiology will require the appropriate GWAS to be conducted in East Asian populations. The detection of genetic associations amongst the 42 CoV-VIPs in a GWAS on contemporary East Asians would provide further evidence that one or more coronaviruses, or another virus using similar interactions, comprised the selection pressure that drove the observed adaptive response. Moreover, a high-powered GWAS in East Asian populations would be required to identify the loci that currently impact individual variation in COVID-19 etiology in East Asian individuals. Because of these limitations, and because it would be extremely difficult to control for all the other factors that differ across the world (including socioeconomic factors), our results do not represent evidence for any difference in either increased or decreased genetic susceptibility in any human population. Insights into...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.11.16.385401: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources The proximity ratio is described in the STAR Methods. 2019) STARsuggested: (STAR, RRID:SCR_015899)(IntAct) The density of conserved segments (PhastCons) The density of regulatory elements du/goldenPath/hg19/encodeD CC/wgEncodeRegDnaseClus tered The recombination rate (Hinch et al., 2011) https://www.well.ox.ac.uk/~an jali/AAmap/ …IntActsuggested: (IntAct, RRID:SCR_006944)SciScore for 10.1101/2020.11.16.385401: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources The proximity ratio is described in the STAR Methods. 2019) STARsuggested: (STAR, RRID:SCR_015899)(IntAct) The density of conserved segments (PhastCons) The density of regulatory elements du/goldenPath/hg19/encodeD CC/wgEncodeRegDnaseClus tered The recombination rate (Hinch et al., 2011) https://www.well.ox.ac.uk/~an jali/AAmap/ IntActsuggested: (IntAct, RRID:SCR_006944)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
An important limitation of our study is that some of our analyses rely upon comparative datasets that were generated in contemporary human populations that have different ancestries than the East Asian populations where the selected CoV-VIP genes were detected. In particular, both of the eQTL and GWAS datasets come from large studies that are primarily focused on contemporary populations from Europe, and none of the five European populations in our study exhibit the selection signals observed in the genomes of East Asians. Accordingly, more direct confirmation of the causal role of 42 CoV-VIP genes in COVID-19 etiology will require the appropriate GWAS to be conducted in East Asian populations. The detection of genetic associations amongst the 42 CoV-VIPs in a GWAS on contemporary East Asians would provide further evidence that coronaviruses comprised the selection pressure that drove the observed adaptive response. Moreover, a high-powered GWAS in East Asian populations could also identify the putative causal loci that currently impact individual variation in COVID-19 etiology in East Asian individuals. Insights into ancient viral epidemics from modern human genomes A particularly salient feature of the adaptive response observed for the 42 CoV-VIPs is that selection appears to be acting continuously over a 20,000 year period. The activity of a viral pressure over such an extensive time period is not consistent with epidemics that started in recorded human history, which ten...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
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