Pandemic-Scale Phylogenomics Reveals Elevated Recombination Rates in the SARS-CoV-2 Spike Region

Turkahia, Y; Thornlow, Bryan; Hinrichs, Angie S; McBroome, Jakob; Ayala, Nicolás; C, Ye; Maio, Nicola De; Haussler, David; Lanfear, Robert; Corbett-Detig, Russell

doi:10.1101/2021.08.04.455157

Cited by 45 publications

(42 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, studying the dynamics of the mutations, rather than the variants, can provide greater insight. For example, as recombination is common in coronaviruses [75], including SARS-CoV-2 [e.g., [76][77][78], one pressing question is whether it will produce a variant that is both highly transmissible/virulent and exhibits vaccineescape [76,79]. Although this is a worrisome possibility, our mutation-centered analysis emphasizes that such a variant need not be 'fitter': depending upon the vaccine protections, these two adaptations (mutations) may produce negative epistasis and so be disfavoured in combination.…”

Section: Discussionmentioning

confidence: 99%

Multilocus adaptation to vaccination

McLeod

Gandon

2021

Preprint

View full text Add to dashboard Cite

Pathogen adaptation to public health interventions, such as vaccination, may take tortuous routes and involve a multitude of genetic mutations acting on distinct phenotypic traits. For example, pathogens can escape the vaccine-induced immune response, or adjust their virulence so as to increase transmission in vaccinated hosts. Despite its importance for public health and vaccine efficacy, how these two adaptations jointly evolve is poorly understood. Taking a trait-centered, rather than variant-centered perspective, here we elucidate the role played by epistasis and recombination, with an emphasis on the different protective effects of vaccination. Vaccines reducing transmission and/or increasing clearance generate positive epistasis between the vaccine-escape and virulence alleles, favouring strains that carry both mutations. Vaccines reducing virulence mortality generate negative epistasis, favouring strains that carry either mutation, but not both. If epistasis is positive, recombination can lead to the sequential fixation of the two mutations and prevent the transient build-up of more virulent escape strains. If epistasis is negative, recombination between loci can create an evolutionary bistability between alternative routes of adaptation, such that whichever adaptation is more accessible tends to be favoured in the long-term. More generally, our model provides a valuable framework for studying pathogen adaptation from a trait-centered view, shifting the focus away from variants.

show abstract

Section: Discussionmentioning

confidence: 99%

Multilocus adaptation to vaccination

McLeod

Gandon

2021

Preprint

View full text Add to dashboard Cite

show abstract

“…24 Recombination between SARS-CoV-2 lineages in the context of simultaneous co-infection has been observed, with particularly high recombination rates seen in the Spike protein sequence. 22,25 The ins214EPE could have been acquired by template switching involving the genomes of SARS-CoV-2, other viruses that infect the same host cells as SARS-CoV-2, or the human transcriptome of host cells infected with SARS-CoV-2. Indeed, there have been clinical reports of COVID-19 patients also being infected with seasonal coronaviruses such as HCoV-229E 26 .…”

Section: Origin Of Insepe In Omicron Potentially Due To Template Switching Using Genome Of Co-infecting Viruses or Hostmentioning

confidence: 99%

Omicron variant of SARS-CoV-2 harbors a unique insertion mutation of putative viral or human genomic origin

Venkatakrishnan¹,

Anand²,

Lenehan³

et al. 2021

Preprint

View full text Add to dashboard Cite

The emergence of a heavily mutated SARS-CoV-2 variant (B.1.1.529, Omicron) and it’s spread to 6 continents within a week of initial discovery has set off a global public health alarm. Characterizing the mutational profile of Omicron is necessary to interpret its shared or distinctive clinical phenotypes with other SARS-CoV-2 variants. We compared the mutations of Omicron with prior variants of concern (Alpha, Beta, Gamma, Delta), variants of interest (Lambda, Mu, Eta, Iota and Kappa), and all 1523 SARS-CoV-2 lineages constituting 5.4 million SARS-CoV-2 genomes. Omicron’s Spike protein has 26 amino acid mutations (23 substitutions, two deletions and one insertion) that are distinct compared to other variants of concern. Whereas the substitution and deletion mutations have appeared in previous SARS-CoV-2 lineages, the insertion mutation (ins214EPE) has not been previously observed in any SARS-CoV-2 lineage other than Omicron. The nucleotide sequence encoding for ins214EPE could have been acquired by template switching involving the genomes of other viruses that infect the same host cells as SARS-CoV-2 or the human transcriptome of host cells infected with SARS-CoV-2. For instance, given recent clinical reports of co-infections in COVID-19 patients with seasonal coronaviruses (e.g. HCoV-229E), single cell RNA-sequencing data showing co-expression of the SARS-CoV-2 and HCoV-229E entry receptors (ACE2 and ANPEP) in respiratory and gastrointestinal cells, and HCoV genomes harboring sequences homologous to the nucleotide sequence that encodes ins214EPE, it is plausible that the Omicron insertion could have evolved in a co-infected individual. There is a need to understand the function of the Omicron insertion and whether human host cells are being exploited by SARS-CoV-2 as an ‘evolutionary sandbox’ for host-virus and inter-viral genomic interplay.

show abstract

“…Detecting recombination from viral genomes is so computationally demanding that prior tools could only handle up to a few thousand viral sequences – a far cry from the scale of millions that is needed to study SARS-CoV-2 recombination comprehensively. We show here how our tools UShER and RIPPLES ( Turakhia, Thornlow, A Hinrichs, et al, 2021 ) empower individual research labs to provide a real-time response, not only in incorporating their sequences onto a global phylogeny, but also in uncovering evidence for recombination from a massive search space. RIPPLES can also be used in an HPC setting to comprehensively detect recombination events from the entire SARS-CoV-2 phylogeny within a few hours.…”

Section: Overview Of the Problemmentioning

confidence: 99%

Pandemic-scale phylogenetics

Cheng

Thornlow

Krämer

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Phylogenetics has been central to the genomic surveillance, epidemiology and contact tracing efforts during the COVD-19 pandemic. But the massive scale of genomic sequencing has rendered the pre-pandemic tools inadequate for comprehensive phylogenetic analyses. Here, we discuss the phylogenetic package that we developed to address the needs imposed by this pandemic. The package incorporates several pandemic-specific optimization and parallelization techniques and comprises four programs: UShER, matOptimize, RIPPLES and matUtils. Using high-performance computing, UShER and matOptimize maintain and refine daily a massive mutation-annotated phylogenetic tree consisting of all SARS-CoV-2 sequences available in online repositories. With UShER and RIPPLES, individual labs -- even with modest compute resources -- incorporate newly-sequenced SARS-CoV-2 genomes on this phylogeny and discover evidence for recombination in real-time. With matUtils, they rapidly query and visualize massive SARS-CoV-2 phylogenies. These tools have empowered scientists worldwide to study the SARS-CoV-2 evolution and transmission at an unprecedented scale, resolution and speed.

show abstract

Pandemic-Scale Phylogenomics Reveals Elevated Recombination Rates in the SARS-CoV-2 Spike Region

Cited by 45 publications

References 35 publications

Multilocus adaptation to vaccination

Multilocus adaptation to vaccination

Omicron variant of SARS-CoV-2 harbors a unique insertion mutation of putative viral or human genomic origin

Pandemic-scale phylogenetics

Contact Info

Product

Resources

About