Transmission of SARS-CoV-2 from humans to animals and potential host adaptation
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Abstract
SARS-CoV-2, the agent of the COVID-19 pandemic, can infect a wide range of mammals. Since its spread in humans, secondary host jumps of SARS-CoV-2 from humans to a variety of domestic and wild populations of mammals have been documented. The evolution of SARS-CoV-2 in different host species is of fundamental interest while also providing indication of how SARS-CoV-2 may have adapted to human hosts soon after the initial host jump, a time window for which there are no genome sequences available. Moreover, the study of SARS-CoV-2 circulating in animals is critical to assess the risk that the transmission of animal-adapted viral lineages back into humans (i.e., spillback) may pose. Here, we compared the genomic landscapes of SARS-CoV-2 isolated from animal species relative to that in humans, profiling the mutational biases indicative of potentially different selective pressures in animals. We focused on viral genomes collected in infected mink ( Neovison vison ) and white-tailed deer ( Odocoileus virginianus ) for which reports of multiple independent spillover events and subsequent animal-to-animal transmission are available. We identified six candidate mutations for animal-specific adaptation in mink (NSP9_G37E, Spike_F486L, Spike_N501T, Spike_Y453F, ORF3a_T229I, ORF3a_L219V), and one in deer (NSP3a_L1035F), though these mutations appear to confer minimal advantage for circulation in humans. Additionally, circulation of SARS-CoV-2 in mink and deer has not caused considerable changes to the evolutionary trajectory of SARS-CoV-2 thus far. Finally, our results suggest that minimal adaptation was required for human-to-animal spillover and subsequent onward transmission in mink and deer, highlighting the ‘generalist’ nature of SARS-CoV-2 as a pathogen of mammalian hosts.
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SciScore for 10.1101/2020.11.16.384743: (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 All genome assemblies were profile aligned to the SARS-CoV-2 reference genome Wuhan-Hu-1 (NC_045512.2) using MAFFT v7.20550. MAFFTsuggested: (MAFFT, RRID:SCR_011811)We constructured a maximum likelihood phylogenetic tree over the 55,030 included genomes using IQ-TREE v2.1.0 Covid release54 specifying the fast mode. IQ-TREEsuggested: (IQ-TREE, RRID:SCR_017254)Trees were queried and plotted using the R packages Ape v5.456 and ggtree v1.16.657 (see Figure 1). Apesuggested: (APE, RRID:SCR_009122)This was done by retrieving the amino acid changes corresponding to all SNPs at these positions using … SciScore for 10.1101/2020.11.16.384743: (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 All genome assemblies were profile aligned to the SARS-CoV-2 reference genome Wuhan-Hu-1 (NC_045512.2) using MAFFT v7.20550. MAFFTsuggested: (MAFFT, RRID:SCR_011811)We constructured a maximum likelihood phylogenetic tree over the 55,030 included genomes using IQ-TREE v2.1.0 Covid release54 specifying the fast mode. IQ-TREEsuggested: (IQ-TREE, RRID:SCR_017254)Trees were queried and plotted using the R packages Ape v5.456 and ggtree v1.16.657 (see Figure 1). Apesuggested: (APE, RRID:SCR_009122)This was done by retrieving the amino acid changes corresponding to all SNPs at these positions using a custom Biopython (v1.76) script (https://github.com/cednotsed/mink_homoplasies/blob/main/dnds/snp_to_sav_parser.py) with annotations reported in Table S3. Biopythonsuggested: (Biopython, RRID:SCR_007173)Assemblies were also uploaded to CoVSurver (https://www.gisaid.org/epiflu-applications/covsurver-mutations-app/) to report the prevalence of mutations and indels relative to SARS-CoV-2 assemblies available on the GISAID database48,49. GISAIDsuggested: (GISAID, RRID:SCR_018279)CpG dinucleotide frequencies for both SARS-CoV-2 alignments of genomes isolated from human and mink were also calculated using a custom R script (https://github.com/cednotsed/mink_homoplasies/blob/main/CpG/plot_CpG.R) (Figure S6). SARS-CoV-2suggested: (Active Motif Cat# 91351, RRID:AB_2847848)Identification of recurrent mutations: We screened for the presence of recurrent mutations in the mink SARS-CoV-2 masked alignment using HomoplasyFinder v0.0.0.960, as described in our previous work61,62. HomoplasyFindersuggested: (HomoplasyFinder, RRID:SCR_017300)We visualised this structure using PyMOL v2.4.166. PyMOLsuggested: (PyMOL, RRID:SCR_000305)We generated query–template alignments using HH-suite67 and predicted 3D models using MODELLER v.9.2468. MODELLERsuggested: (MODELLER, RRID:SCR_008395)Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.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.
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 10.1101/2020.11.16.384743: (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 All genome assemblies were profile aligned to the SARSCoV-2 reference genome Wuhan-Hu-1 (NC_045512.2) using MAFFT v7.20550. MAFFTsuggested: (MAFFT, RRID:SCR_011811)We constructured a maximum likelihood phylogenetic tree over the 55,030 included genomes using IQ-TREE v2.1.0 Covid release54 specifying the fast mode. …IQ-TREEsuggested: (IQ-TREE, RRID:SCR_017254)SciScore for 10.1101/2020.11.16.384743: (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 All genome assemblies were profile aligned to the SARSCoV-2 reference genome Wuhan-Hu-1 (NC_045512.2) using MAFFT v7.20550. MAFFTsuggested: (MAFFT, RRID:SCR_011811)We constructured a maximum likelihood phylogenetic tree over the 55,030 included genomes using IQ-TREE v2.1.0 Covid release54 specifying the fast mode. IQ-TREEsuggested: (IQ-TREE, RRID:SCR_017254)Trees were queried and plotted using the R packages Ape v5.456 and ggtree v1.16.657 (see Figure 1). Apesuggested: (APE, RRID:SCR_009122)This was done by retrieving the amino acid changes corresponding to all SNPs at these positions using a custom Biopython (v1.76) script (https://github.com/cednotsed/mink_homoplasies/blob/main/dnds/snp_to_sav_parser.py) with annotations reported in Table S3. Biopythonsuggested: (Biopython, RRID:SCR_007173)CpG dinucleotide frequencies for both SARS-CoV-2 alignments of genomes isolated from human and mink were also calculated using a custom R script (https://github.com/cednotsed/mink_homoplasies/blob/main/CpG/plot_CpG.R) (Figure S6). SARS-CoV-2suggested: (SARS-CoV-2-Sequences, RRID:SCR_018319)Identification of recurrent mutations We screened for the presence of recurrent mutations in the mink SARS-CoV-2 masked alignment using HomoplasyFinder v0.0.0.960, as described in our previous work61,62. HomoplasyFindersuggested: (HomoplasyFinder, RRID:SCR_017300)We generated query–template alignments using HH-suite67 and predicted 3D models using MODELLER v.9.2468. MODELLERsuggested: (MODELLER, RRID:SCR_008395)This figure was rendered using PyMOL (v2.4.1). PyMOLsuggested: (PyMOL, RRID:SCR_000305)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.
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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