Coronavirus genomes carry the signatures of their habitats

Wei, Yulong; Silke, Jordan R.; Aris, Parisa; Xia, Xuhua

doi:10.1101/2020.06.13.149591

Cited by 16 publications

(21 citation statements)

References 62 publications

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“…Our CpG net gain analysis showed a decline, indicating that the number of total CpG losses overrides their gain (Figure S4), in agreement with recently published observations (Wang et al 2020; Wei et al 2020; Zhang et al 2020). Similar to other coronavirus genomes, SARS-CoV-2 has a low CpG frequency around 1.5%, while the expected frequency is 3.6% (Wang et al 2020).…”

Section: Resultssupporting

confidence: 92%

“…The remaining dinucleotides showed relative stability across the time period. Interestingly, recent reports showed the reduction of CpG dinucleotides in 5’-UTR and ORF1ab regions (Wang et al 2020; Wei et al 2020; Zhang et al 2020). When analyzing the context of genomic sites undergoing C>U changes we noticed an enrichment for 5’-UCG-3’ motifs (Table S2).…”

Section: Resultsmentioning

confidence: 99%

“…The conversion of C>U allows viral RNA to escape from ZAP-mediated RNA destruction. A recent study hypothesized that both ZAP and APOBEC provide selective pressure that drives the adaptation of SARS-CoV-2 to its host (Wei et al 2020). Here we provided one of the potential mechanisms that contribute to CpG reduction in SARS-CoV-2.…”

Section: Resultsmentioning

confidence: 99%

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Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction

Sadykov

Mourier

Guan

et al. 2020

Preprint

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RNA viruses use CpG reduction to evade the host cell defense, but the driving mechanism is still largely unknown. To address this, we used a rapidly growing genomic dataset of SARS-CoV-2 with relevant metadata information. SARS-CoV-2 genomes show a progressive increase of C-to-U substitutions resulting in CpG loss over just a few months. This is consistent with APOBEC-mediated RNA editing resulting in CpG reduction, thus allowing the virus to escape ZAP-mediated RNA degradation. Our results thus link the dynamics of target sequences in the viral genome for two known host molecular defense mechanisms, mediated by the APOBEC and ZAP proteins.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

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Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction

Sadykov

Mourier

Guan

et al. 2020

Preprint

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“…This finding supports our prediction that recognition of SARS-CoV-2 by ZAP imposes a significant fitness cost on the virus, as demonstrated by its early evolution to remove ZAP recognition motifs. Two other recent theoretical works [38,39], corroborate our results showing that at the single nucleotide level there is a net prevalence of C→U synonymous mutations (the most common nucleotide mutation which may cause a CpG loss) in the early evolution of SARS-CoV-2. Moreover a recent analysis of the immune profile of patients with moderate and severe disease revealed an association between early, elevated cytokines and worse disease outcomes identifying a maladapted immune response profile associated with severe COVID-19 outcome [40].…”

Section: Discussionsupporting

confidence: 90%

The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2

Gioacchino

Šulc

Komarova

et al. 2020

Preprint

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SARS-CoV-2 infection can lead to acute respiratory syndrome in patients, which can be due in part to dysregulated immune signalling. We analyze here the occurrences of CpG and UpA dinucleotides, which are putative pathogen-associated molecular patterns, along the viral sequence. Carrying out a comparative analysis with other ssRNA viruses and within the Coronaviridae family, we find the CpG content of SARS-CoV-2, while low compared to other betacoronaviruses, widely fluctuates along its primary sequence. While the CpG relative abundance and its associated CpG force parameter [1] are low for the spike protein (S) and comparable to circulating seasonal coronaviruses such as HKU1, they are much greater and comparable to SARS and MERS for the 3'-end of the viral genome. In particular, the nucleocapsid protein (N), whose transcripts are relatively abundant in the cytoplasm of infected cells and present in the 3'UTRs of all subgenomic RNA, has high CpG content. We speculate this dual nature of CpG content can confer to SARS-CoV-2 high ability to both enter the host and trigger pattern recognition receptors (PRRs) in different contexts. We then investigate the evolution of synonymous mutations since the outbreak of the COVID-19 pandemic. Using a new application of selective forces on dinucleotides to estimate context driven mutational processes, we find that synonymous mutations seem driven both by the viral codon bias and by the high value of the CpG force in the N protein, leading to a loss in CpG content. Sequence motifs preceding these CpG-loss-associated loci match recently identified binding patterns of the Zinc Finger anti-viral Protein (ZAP) protein.

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“…Regarding the NCBI reference genome (GenBank ID: NC_045512) 46 , this sample was collected on 26 December 2019 47 . The collection date for the GISAID reference genome (GenBank ID: MN908947) is listed as 31 December 2019 48 , although the patient was reported sick and admitted into the hospital on 26 December 2019 46 . Thus, in our analyses, we used the GISAID collection date of 31 December 2019 for the GISAID reference genome to be consistent with previous studies.…”

Section: Reference Genomes and Collection Datesmentioning

confidence: 99%

An evolutionary portrait of the progenitor SARS-CoV-2 and its dominant offshoots in COVID-19 pandemic

Kumar

Tao

Weaver

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, was quickly identified as the cause of COVID-19 disease soon after its earliest reports. The knowledge of the contemporary evolution of SARS-CoV-2 is urgently needed not only for a retrospective on how, when, and why COVID-19 has emerged and spread, but also for creating remedies through efforts of science, technology, medicine, and public policy. Global sequencing of thousands of genomes has revealed many common genetic variants, which are the key to unraveling the early evolutionary history of SARS-CoV-2 and tracking its global spread over time. However, our knowledge of fundamental events in the evolution and spread of this coronavirus remains grossly incomplete and highly uncertain. Here, we present the heretofore cryptic mutational history, phylogeny, and dynamics of SARS-CoV-2 from an analysis of tens of thousands of high-quality genomes. The reconstructed mutational progression is highly concordant with the timing of coronavirus sampling dates. It predicts the progenitor genome whose earliest offspring without any non-synonymous mutations were still spreading worldwide months after the report of COVID-19. Over time, mutations gave rise to seven major lineages that spread episodically, some of which arose in Europe and North America after the genesis of the ancestral lineages in China. Mutational barcoding establishes that North American coronaviruses harbor very different genome signatures than coronaviruses prevalent in Europe and Asia that have converged over time. These spatiotemporal patterns continue to evolve as the pandemic progresses and can be viewed live online.

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Coronavirus genomes carry the signatures of their habitats

Abstract: 9Coronaviruses such as SARS-CoV-2 regularly infect host tissues that express antiviral proteins 10

Cited by 16 publications

References 62 publications

Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction

Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction

The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2

An evolutionary portrait of the progenitor SARS-CoV-2 and its dominant offshoots in COVID-19 pandemic

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