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  1. Article ; Online: Exploring the Natural Origins of SARS-CoV-2 in the Light of Recombination.

    Lytras, Spyros / Hughes, Joseph / Martin, Darren / Swanepoel, Phillip / de Klerk, Arné / Lourens, Rentia / Kosakovsky Pond, Sergei L / Xia, Wei / Jiang, Xiaowei / Robertson, David L

    Genome biology and evolution

    2022  Volume 14, Issue 2

    Abstract: The lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2, and the large geographical distance between Wuhan and where the closest evolutionary related coronaviruses circulating in horseshoe bats (members of the ...

    Abstract The lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2, and the large geographical distance between Wuhan and where the closest evolutionary related coronaviruses circulating in horseshoe bats (members of the Sarbecovirus subgenus) have been identified, is fueling speculation on the natural origins of SARS-CoV-2. We performed a comprehensive phylogenetic study on SARS-CoV-2 and all the related bat and pangolin sarbecoviruses sampled so far. Determining the likely recombination events reveals a highly reticulate evolutionary history within this group of coronaviruses. Distribution of the inferred recombination events is nonrandom with evidence that Spike, the main target for humoral immunity, is beside a recombination hotspot likely driving antigenic shift events in the ancestry of bat sarbecoviruses. Coupled with the geographic ranges of their hosts and the sampling locations, across southern China, and into Southeast Asia, we confirm that horseshoe bats, Rhinolophus, are the likely reservoir species for the SARS-CoV-2 progenitor. By tracing the recombinant sequence patterns, we conclude that there has been relatively recent geographic movement and cocirculation of these viruses' ancestors, extending across their bat host ranges in China and Southeast Asia over the last 100 years. We confirm that a direct proximal ancestor to SARS-CoV-2 has not yet been sampled, since the closest known relatives collected in Yunnan shared a common ancestor with SARS-CoV-2 approximately 40 years ago. Our analysis highlights the need for dramatically more wildlife sampling to: 1) pinpoint the exact origins of SARS-CoV-2's animal progenitor, 2) the intermediate species that facilitated transmission from bats to humans (if there is one), and 3) survey the extent of the diversity in the related sarbecoviruses' phylogeny that present high risk for future spillovers.
    MeSH term(s) Animals ; Chiroptera/virology ; Coronavirus/genetics ; Humans ; Pangolins/virology ; Phylogeny ; Phylogeography ; Recombination, Genetic
    Language English
    Publishing date 2022-02-11
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2495328-3
    ISSN 1759-6653 ; 1759-6653
    ISSN (online) 1759-6653
    ISSN 1759-6653
    DOI 10.1093/gbe/evac018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Conserved recombination patterns across coronavirus subgenera.

    de Klerk, Arné / Swanepoel, Phillip / Lourens, Rentia / Zondo, Mpumelelo / Abodunran, Isaac / Lytras, Spyros / MacLean, Oscar A / Robertson, David / Kosakovsky Pond, Sergei L / Zehr, Jordan D / Kumar, Venkatesh / Stanhope, Michael J / Harkins, Gordon / Murrell, Ben / Martin, Darren P

    Virus evolution

    2022  Volume 8, Issue 2, Page(s) veac054

    Abstract: Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of ... ...

    Abstract Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of recombination in coronaviruses are non-random and that this is likely attributable to a combination of sequence features that favour the occurrence of recombination break points at specific genomic sites, and selection disfavouring the survival of recombinants within which favourable intra-genome interactions have been disrupted. Here we leverage available whole-genome sequence data for six coronavirus subgenera to identify specific patterns of recombination that are conserved between multiple subgenera and then identify the likely factors that underlie these conserved patterns. Specifically, we confirm the non-randomness of recombination break points across all six tested coronavirus subgenera, locate conserved recombination hot- and cold-spots, and determine that the locations of transcriptional regulatory sequences are likely major determinants of conserved recombination break-point hotspot locations. We find that while the locations of recombination break points are not uniformly associated with degrees of nucleotide sequence conservation, they display significant tendencies in multiple coronavirus subgenera to occur in low guanine-cytosine content genome regions, in non-coding regions, at the edges of genes, and at sites within the Spike gene that are predicted to be minimally disruptive of Spike protein folding. While it is apparent that sequence features such as transcriptional regulatory sequences are likely major determinants of where the template-switching events that yield recombination break points most commonly occur, it is evident that selection against misfolded recombinant proteins also strongly impacts observable recombination break-point distributions in coronavirus genomes sampled from nature.
    Language English
    Publishing date 2022-06-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/veac054
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Conserved recombination patterns across coronavirus subgenera

    de Klerk, Arne / Swanepoel, Phillip Ivan / Lourens, Rentia Francis / Zondo, Mpumelelo / Abodunran, Isaac / Lytras, Spyros / MacLean, Oscar / Robertson, David L / Kosakovsky Pond, Sergei L / Zehr, Jordan D / Kumar, Venkatesh / Stanhope, Michael J / Harkins, Gordon / Murrell, Ben / Martin, Darren

    bioRxiv

    Abstract: Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of ... ...

    Abstract Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of recombination in coronaviruses are non-random and that this is likely attributable to a combination of sequence features that favour the occurrence of recombination breakpoints at specific genomic sites, and selection disfavouring the survival of recombinants within which favourable intra-genome interactions have been disrupted. Here we leverage available whole-genome sequence data for six coronavirus subgenera to identify specific patterns of recombination that are conserved between multiple subgenera and then identify the likely factors that underlie these conserved patterns. Specifically, we confirm the non-randomness of recombination breakpoints across all six tested coronavirus subgenera, locate conserved recombination hot- and cold-spots, and determine that the locations of transcriptional regulatory sequences are likely major determinants of conserved recombination breakpoint hot-spot locations. We find that while the locations of recombination breakpoints are not uniformly associated with degrees of nucleotide sequence conservation, they display significant tendencies in multiple coronavirus subgenera to occur in low guanine-cytosine content genome regions, in non-coding regions, at the edges of genes, and at sites within the Spike gene that are predicted to be minimally disruptive of Spike protein folding. While it is apparent that sequence features such as transcriptional regulatory sequences are likely major determinants of where the template-switching events that yield recombination breakpoints most commonly occur, it is evident that selection against misfolded recombinant proteins also strongly impacts observable recombination breakpoint distributions in coronavirus genomes sampled from nature.
    Keywords covid19
    Language English
    Publishing date 2021-11-23
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2021.11.21.469423
    Database COVID19

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  4. Article: Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function.

    Martin, Darren P / Lytras, Spyros / Lucaci, Alexander G / Maier, Wolfgang / Grüning, Björn / Shank, Stephen D / Weaver, Steven / MacLean, Oscar A / Orton, Richard J / Lemey, Philippe / Boni, Maciej F / Tegally, Houriiyah / Harkins, Gordon / Scheepers, Cathrine / Bhiman, Jinal N / Everatt, Josie / Amoako, Daniel G / San, James Emmanuel / Giandhari, Jennifer /
    Sigal, Alex / Williamson, Carolyn / Hsiao, Nei-Yuan / von Gottberg, Anne / De Klerk, Arne / Shafer, Robert W / Robertson, David L / Wilkinson, Robert J / Sewell, B Trevor / Lessells, Richard / Nekrutenko, Anton / Greaney, Allison J / Starr, Tyler N / Bloom, Jesse D / Murrell, Ben / Wilkinson, Eduan / Gupta, Ravindra K / de Oliveira, Tulio / Kosakovsky Pond, Sergei L

    bioRxiv : the preprint server for biology

    2022  

    Abstract: Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely ... ...

    Abstract Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any genomes within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.
    Language English
    Publishing date 2022-01-18
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2022.01.14.476382
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Selection Analysis Identifies Clusters of Unusual Mutational Changes in Omicron Lineage BA.1 That Likely Impact Spike Function.

    Martin, Darren P / Lytras, Spyros / Lucaci, Alexander G / Maier, Wolfgang / Grüning, Björn / Shank, Stephen D / Weaver, Steven / MacLean, Oscar A / Orton, Richard J / Lemey, Philippe / Boni, Maciej F / Tegally, Houriiyah / Harkins, Gordon W / Scheepers, Cathrine / Bhiman, Jinal N / Everatt, Josie / Amoako, Daniel G / San, James Emmanuel / Giandhari, Jennifer /
    Sigal, Alex / Williamson, Carolyn / Hsiao, Nei-Yuan / von Gottberg, Anne / De Klerk, Arne / Shafer, Robert W / Robertson, David L / Wilkinson, Robert J / Sewell, B Trevor / Lessells, Richard / Nekrutenko, Anton / Greaney, Allison J / Starr, Tyler N / Bloom, Jesse D / Murrell, Ben / Wilkinson, Eduan / Gupta, Ravindra K / de Oliveira, Tulio / Kosakovsky Pond, Sergei L

    Molecular biology and evolution

    2022  Volume 39, Issue 4

    Abstract: Among the 30 nonsynonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely ... ...

    Abstract Among the 30 nonsynonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (1) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (2) interactions of Spike with ACE2 receptors, and (3) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any virus within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and, in combination with other mutations, adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron overall previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.
    MeSH term(s) COVID-19/genetics ; Humans ; Mutation ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/genetics
    Chemical Substances Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2022-03-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 998579-7
    ISSN 1537-1719 ; 0737-4038
    ISSN (online) 1537-1719
    ISSN 0737-4038
    DOI 10.1093/molbev/msac061
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  6. Article ; Online: Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function

    Martin, Darren P / Lytras, Spyro / Lucaci, Alexander G / Maier, Wolfgang / Gruning, Bjorn / Shank, Stephen D / Weaver, Steven / MacLean, Oscar S / Orton, Richard J / Lemey, Philippe / Boni, Maciej F / Tegally, Houriiyah / Harkins, Gordon W / Scheepers, Cathrine / Bhiman, Jinal N / Everatt, Josie / Amoako, Daniel G / San, James Emmanuel / Giandhari, Jennifer /
    Sigal, Alex / NGS-SA / Williamson, Carolyn / Hsiao, Nei-yuan / von Gottberg, Anne / De Klerk, Arne / Shafer, Robert W / Robertson, David L / Wilkinson, Robert J / Sewell, Brian Trevor / Lessells, Richard / Nekrutenko, Anton / Greaney, Allison J / Starr, Tyler N / Bloom, Jesse D / Murrell, Ben / Wilkinson, Eduan / Gupta, Ravindra K / de Oliveira, Tulio / Kosakovsky Pond, Sergei L

    bioRxiv

    Abstract: Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely ... ...

    Abstract Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any virus within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and, in combination with other mutations, adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.
    Keywords covid19
    Language English
    Publishing date 2022-01-18
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2022.01.14.476382
    Database COVID19

    Full text online

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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