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

Sadykov, Mukhtar; Mourier, Tobias; Guan, Qingtian; Pain, Arnab

doi:10.1101/2020.06.19.161687

Cited by 3 publications

(4 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This confirms previous results which suggested an elevated U C G→U U G mutation rate [ 32 , 16 , 5 ], attributed to either the context-specificity of APOBEC mutational targets, or to selection against CpG dinucleotides [ 15 ]. We discuss selection in the next section.…”

Section: Resultssupporting

confidence: 92%

“…Genomic SARS-CoV-2 data also allows us to investigate the evolutionary dynamics of the virus such as its mutational and selective pressures [ 5 ]. Understanding the contribution of mutation and selection in shaping SARS-CoV-2 genome evolution is important, for example, for drug and vaccine development [ 6 ], for predicting variants of clinical and epidemiological importance [ 7 , 8 , 9 , 10 , 11 ], for understanding the biological mechanisms underlying the virus’ genome evolution (such as recombination [ 12 ] and mutagenic immune system responses [ 13 , 14 , 15 , 16 ]), to improve the accuracy of phylogenetic approaches for epidemiological applications [ 17 , 18 , 19 ] and for inferring its origin [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mutation rates and selection on synonymous mutations in SARS-CoV-2

Maio

Walker

Turakhia

et al. 2021

Preprint

View full text Add to dashboard Cite

The COVID-19 pandemic has seen an unprecedented response from the sequencing community. Leveraging the sequence data from more than 140,000 SARS-CoV-2 genomes, we study mutation rates and selective pressures affecting the virus. Understanding the processes and effects of mutation and selection has profound implications for the study of viral evolution, for vaccine design, and for the tracking of viral spread. We highlight and address some common genome sequence analysis pitfalls that can lead to inaccurate inference of mutation rates and selection, such as ignoring skews in the genetic code, not accounting for recurrent mutations, and assuming evolutionary equilibrium. We find that two particular mutation rates, G→U and C→U, are similarly elevated and considerably higher than all other mutation rates, causing the majority of mutations in the SARS-CoV-2 genome, and are possibly the result of APOBEC and ROS activity. These mutations also tend to occur many times at the same genome positions along the global SARS-CoV-2 phylogeny (i.e., they are very homoplasic). We observe an effect of genomic context on mutation rates, but the effect of the context is overall limited. While previous studies have suggested selection acting to decrease U content at synonymous sites, we bring forward evidence suggesting the opposite.

show abstract

Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Mutation rates and selection on synonymous mutations in SARS-CoV-2

Maio

Walker

Turakhia

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…ZAP, along with Trim25 and PARP12 (discussed in the PARP12 section and below), directly bind SARS-CoV-2 RNA [ 83 ]. To counter ZAP targeting, SARS-CoV-2 shows evidence of CpG suppression over the course of a 5-month study [ 104 ]. Furthermore, phylogenetic mutation analysis suggests that C and G mutations are reflective of SARS-CoV-2's attempts to counter host defense systems such as ZAP targeting [ 105 ].…”

Section: The Roles Of Parps In Viral Infectionmentioning

confidence: 99%

NAD+-consuming enzymes in immune defense against viral infection

Shang

Smith

Anmangandla

et al. 2021

Biochemical Journal

View full text Add to dashboard Cite

The COVID-19 pandemic reminds us that in spite of the scientific progress in the past century, there is a lack of general antiviral strategies. In analogy to broad-spectrum antibiotics as antibacterial agents, developing broad spectrum antiviral agents would buy us time for the development of vaccines and treatments for future viral infections. In addition to targeting viral factors, a possible strategy is to understand host immune defense mechanisms and develop methods to boost the antiviral immune response. Here we summarize the role of NAD+-consuming enzymes in the immune defense against viral infections, with the hope that a better understanding of this process could help to develop better antiviral therapeutics targeting these enzymes. These NAD+-consuming enzymes include PARPs, sirtuins, CD38, and SARM1. Among these, the antiviral function of PARPs is particularly important and will be a focus of this review. Interestingly, NAD+ biosynthetic enzymes are also implicated in immune responses. In addition, many viruses, including SARS-CoV-2 contain a macrodomain-containing protein (NSP3 in SARS-CoV-2), which serves to counteract the antiviral function of host PARPs. Therefore, NAD+ and NAD+-consuming enzymes play crucial roles in immune responses against viral infections and detailed mechanistic understandings in the future will likely facilitate the development of general antiviral strategies.

show abstract

“…APOBEC, typically considered an antiviral mechanism against retroviruses, may also mediate antiviral functions against RNA viruses, since it catalyzes cytosine deamination to uracil in foreign ssDNA and RNA [ 22 ]. Extensive C-to-U mutations, the genomic context of which was enriched for APOBEC target sites [ 23 ], have been observed in SARS-CoV-2 since the early phases of the pandemic [ 24 , 25 ]. Interestingly, only viruses regularly infecting tissues with high expression of APOBEC and other antiviral proteins exhibited CpG-depletion and U-rich genomes [ 26 ].…”

Section: The Selection Pressure To Escape From Host Immune Responsesmentioning

confidence: 99%