scholarly journals Evolution of Nucleotide Composition in the SARS-CoV-2 Lineage: Implications for Vaccine Design

Author(s):  
Sankar Subramanian

The worldwide outbreak of a novel coronavirus, SARS-CoV-2 has caused a pandemic of respiratory disease. Due to this emergency, researchers around the globe have been investigating the evolution of the genome of SARS-CoV-2 in order to design vaccines. Here I examined the evolution of GC content of SARS-CoV-2 by comparing the genomes of the members of the group Betacoronavirus. The results of this investigation revealed a highly significant positive correlation between the GC contents of betacoronaviruses and their divergence from SARS-CoV-2. The betacoronaviruses that are distantly related to SARS-CoV-2 have much higher GC contents than the latter. Conversely, the closely related ones have low GC contents, which are only slightly higher than that of SARS-CoV-2. This suggests a systematic reduction in the GC content in the SARS-CoV-2 lineage over time. The declining trend in this lineage predicts a much-reduced GC content in the coronaviruses that will descend/evolve from SARS-CoV-2 in the future. Due to the three consecutive outbreaks (MERS-CoV, SARS-CoV and SARS-CoV-2) caused by the members of the SARS-CoV-2, the scientific community is emphasizing the need for universal vaccines that are effective across many strains including those, that will inevitably emerge in the near future. The reduction in GC contents implies an increase in the rate of GC→AT mutations than that the mutational changes in the reverse direction. Therefore, understanding the evolution of base composition and mutational patterns of SARS-CoV-2 could be useful in designing broad-spectrum vaccines that could identify and neutralize the present and future strains of this virus.

2008 ◽  
Vol 4 (4) ◽  
pp. 438-441 ◽  
Author(s):  
Penelope R Haddrill ◽  
Brian Charlesworth

The nature of the forces affecting base composition is a key question in genome evolution. There is uncertainty as to whether differences in the GC contents of non-coding sequences reflect differences in mutational bias, or in the intensity of selection or biased gene conversion. We have used a polymorphism dataset for non-coding sequences on the X chromosome of Drosophila simulans to examine this question. The proportion of GC→AT versus AT→GC polymorphic mutations in a locus is correlated with its GC content. This implies the action of forces that favour GC over AT base pairs, which are apparently strongest in GC-rich sequences.


Genome ◽  
2006 ◽  
Vol 49 (5) ◽  
pp. 413-419 ◽  
Author(s):  
Jin-Feng Chen ◽  
Fei Lu ◽  
Su-Shing Chen ◽  
Shi-Heng Tao

This paper establishes that recombination drives the evolution of GC content in a significant way. Because the human P-arm pseudoautosomal region (PAR1) has been shown to have a high recombination rate, at least 20-fold more frequent than the genomic average of ~1 cM/Mb, this region provides an ideal system to study the role of recombination in the evolution of base composition. Nine non-coding regions of PAR1 are analyzed in this study. We have observed a highly significant positive correlation between the recombination rate and GC content (ρ = 0.837, p ≤ 0.005). Five regions that lie in the distal part of PAR1 are shown to be significantly higher than genomic average divergence. By comparing the intra- and inter-specific AT→GC – GC→AT ratios, we have detected no fixation bias toward GC alleles except for L254915, which has excessive AT→GC changes in the human lineage. Thus, we conclude that the high GC content of the PAR1 genes better fits the biased gene conversion (BGC) model.Key words: pseudoautosomal region, GC content, base composition, evolution, recombination.


2021 ◽  
Vol 12 ◽  
Author(s):  
Diego Simón ◽  
Juan Cristina ◽  
Héctor Musto

The genetic material of the three domains of life (Bacteria, Archaea, and Eukaryota) is always double-stranded DNA, and their GC content (molar content of guanine plus cytosine) varies between ≈ 13% and ≈ 75%. Nucleotide composition is the simplest way of characterizing genomes. Despite this simplicity, it has several implications. Indeed, it is the main factor that determines, among other features, dinucleotide frequencies, repeated short DNA sequences, and codon and amino acid usage. Which forces drive this strong variation is still a matter of controversy. For rather obvious reasons, most of the studies concerning this huge variation and its consequences, have been done in free-living organisms. However, no recent comprehensive study of all known viruses has been done (that is, concerning all available sequences). Viruses, by far the most abundant biological entities on Earth, are the causative agents of many diseases. An overview of these entities is important also because their genetic material is not always double-stranded DNA: indeed, certain viruses have as genetic material single-stranded DNA, double-stranded RNA, single-stranded RNA, and/or retro-transcribing. Therefore, one may wonder if what we have learned about the evolution of GC content and its implications in prokaryotes and eukaryotes also applies to viruses. In this contribution, we attempt to describe compositional properties of ∼ 10,000 viral species: base composition (globally and according to Baltimore classification), correlations among non-coding regions and the three codon positions, and the relationship of the nucleotide frequencies and codon usage of viruses with the same feature of their hosts. This allowed us to determine how the base composition of phages strongly correlate with the value of their respective hosts, while eukaryotic viruses do not (with fungi and protists as exceptions). Finally, we discuss some of these results concerning codon usage: reinforcing previous results, we found that phages and hosts exhibit moderate to high correlations, while for eukaryotes and their viruses the correlations are weak or do not exist.


2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Padmalochan Hembram

Abstract Background Coronavirus disease 19 is a viral infection caused by a novel coronavirus, SARS-CoV-2. It was first notified in Wuhan, China, is now spread into numerous part of the world. Thus, the world needs urgent support and encouragement to develop a vaccine or antiviral treatments to combat the atrocious outbreak. Main body of the abstract The origin of this virus is yet unknown; however, rapid transmission from human-to-human “Anthroponosis” has widely confirmed. The world is witnessing a continuous hike in SARS-CoV-2 infection. In light of the outbreak of coronavirus disease 19, we have aimed to highlight the basic and vital information about the novel coronavirus. We provide an overview of SARS-CoV-2 transmission, timeline and its pathophysiological properties which would be an aid for the development of therapeutic molecules and antiviral drugs. Immune system plays a crucial role in virus infection in order to control but may have dark side when becomes uncontrollable. The host and SARS-CoV-2 interaction describe how the virus exploits host machinery and how overactive host immune response can cause disease severity also addressed in this review. Short conclusion Safe and effective vaccines may be the game-changing tools, but in the near future wearing mask, washing hands at regular intervals, avoiding crowed, maintaining physical distancing and hygienic surrounding, must be good practices to reduce and break the transmission chain. Still, research is ongoing not only on how vaccines protect against disease, but also against infection and transmission.


Genetics ◽  
2002 ◽  
Vol 162 (4) ◽  
pp. 1805-1810 ◽  
Author(s):  
Martin J Lercher ◽  
Nick G C Smith ◽  
Adam Eyre-Walker ◽  
Laurence D Hurst

AbstractThe large-scale systematic variation in nucleotide composition along mammalian and avian genomes has been a focus of the debate between neutralist and selectionist views of molecular evolution. Here we test whether the compositional variation is due to mutation bias using two new tests, which do not assume compositional equilibrium. In the first test we assume a standard population genetics model, but in the second we make no assumptions about the underlying population genetics. We apply the tests to single-nucleotide polymorphism data from noncoding regions of the human genome. Both models of neutral mutation bias fit the frequency distributions of SNPs segregating in low- and medium-GC-content regions of the genome adequately, although both suggest compositional nonequilibrium. However, neither model fits the frequency distribution of SNPs from the high-GC-content regions. In contrast, a simple population genetics model that incorporates selection or biased gene conversion cannot be rejected. The results suggest that mutation biases are not solely responsible for the compositional biases found in noncoding regions.


Author(s):  
Andreina I Castillo ◽  
Rodrigo P P Almeida

Abstract Nucleotide composition (GC content) varies across bacteria species, genome regions, and specific genes. In Xylella fastidiosa, a vector-borne fastidious plant pathogen infecting multiple crops, GC content ranges between ∼51-52%; however, these values were gathered using limited genomic data. We evaluated GC content variations across X. fastidiosa subspecies fastidiosa (N = 194), subsp. pauca (N = 107), and subsp. multiplex (N = 39). Genomes were classified based on plant host and geographic origin; individual genes within each genome were classified based on gene function, strand, length, ortholog group, Core vs. Accessory, and Recombinant vs. Non-recombinant. GC content was calculated for each gene within each evaluated genome. The effects of genome and gene level variables were evaluated with a mixed effect ANOVA, and the marginal-GC content was calculated for each gene. Also, the correlation between gene-specific GC content vs. natural selection (dN/dS) and recombination/mutation (r/m) was estimated. Our analyses show that intra-genomic changes in nucleotide composition in X. fastidiosa are small and influenced by multiple variables. Higher AT-richness is observed in genes involved in replication and translation, and genes in the leading strand. In addition, we observed a negative correlation between high-AT and dN/dS in subsp. pauca. The relationship between recombination and GC content varied between core and accessory genes. We hypothesize that distinct evolutionary forces and energetic constraints both drive and limit these small variations in nucleotide composition.


2021 ◽  
Author(s):  
Neetu Tyagi ◽  
Rahila Sardar ◽  
Dinesh Gupta

AbstractThe Coronavirus disease 2019 (COVID-19) outbreak caused by Severe Acute Respiratory Syndrome Coronavirus 2 virus (SARS-CoV-2) poses a worldwide human health crisis, causing respiratory illness with a high mortality rate. To investigate the factors governing codon usage bias in all the respiratory viruses, including SARS-CoV-2 isolates from different geographical locations (~62K), including two recently emerging strains from the United Kingdom (UK), i.e., VUI202012/01 and South Africa (SA), i.e., 501.Y.V2 codon usage bias (CUBs) analysis was performed. The analysis includes RSCU analysis, GC content calculation, ENC analysis, dinucleotide frequency and neutrality plot analysis. We were motivated to conduct the study to fulfil two primary aims: first, to identify the difference in codon usage bias amongst all SARS-CoV-2 genomes and, secondly, to compare their CUBs properties with other respiratory viruses. A biased nucleotide composition was found as most of the highly preferred codons were A/U-ending in all the respiratory viruses studied here. Compared with the human host, the RSCU analysis led to the identification of 11 over-represented codons and 9 under-represented codons in SARS-CoV-2 genomes. Correlation analysis of ENC and GC3s revealed that mutational pressure is the leading force determining the CUBs. The present study results yield a better understanding of codon usage preferences for SARS-CoV-2 genomes and discover the possible evolutionary determinants responsible for the biases found among the respiratory viruses, thus unveils a unique feature of the SARS-CoV-2 evolution and adaptation. To the best of our knowledge, this is the first attempt at comparative CUBs analysis on the worldwide genomes of SARS-CoV-2, including novel emerged strains and other respiratory viruses.


2019 ◽  
Vol 55 (1) ◽  
pp. 260
Author(s):  
Constantinos Perisoratis

The climate changes are necessarily related to the increase of the Earth’s temperature, resulting in a sea level rise. Such continuous events, were taking place with minor and greater intensity, during the alternation of warm and cool periods in the Earth during the Late Quaternary and the Holocene periods. However, a particularly significant awareness has taken place in the scientific community, and consequently in the greater public, in the last decades: that a climatic change will take place soon, or it is on-going, and that therefore it is important to undertake drastic actions. However, such a climatic change has not been recorded yet, and hence the necessary actions are not required, for the time being.


1997 ◽  
Vol 71 (4) ◽  
pp. 325-332 ◽  
Author(s):  
U. Pandya ◽  
J.K. Saxena ◽  
O.P. Shukla

AbstractThe interaction of DNA from filarial parasite Setaria cervi with polyamines was monitored by melting temperature (Tm) profile, condensation and B to Z DNA transition and compared with DNA of Escherichia coli, Micrococcus luteus and calf thymus having different GC content. Polyamines, viz. spermine and spermidine, stabilized the secondary structure of all DNAs as indicated by increase in Tm value. UV absorption studies indicated B to Z DNA transition in the presence of polyamines. The amount of polyamines required for B to Z transition was dependent upon base composition of DNA and charge of the polyamine. Filarial DNA (AT rich) required six times higher concentration of spermine as compared to GC rich DNA for B to Z DNA transition. Spermidine was not effective in causing transition of S. cervi DNA even at Spd:DNA-P ratio of 20. The antifilarial compound suramin significantly decreased melting temperature of filarial DNA as compared to GC rich DNAs of other parasites. Suramin adversely affected condensation and B to Z DNA transition of various DNAs but prior addition of polyamines protected the DNAs from the destabilizing effect of suramin.


2016 ◽  
Vol 23 (1) ◽  
pp. 132-140 ◽  
Author(s):  
Filippo Bencivenga ◽  
Marco Zangrando ◽  
Cristian Svetina ◽  
Alessandro Abrami ◽  
Andrea Battistoni ◽  
...  

The recent advent of free-electron laser (FEL) sources is driving the scientific community to extend table-top laser research to shorter wavelengths adding elemental selectivity and chemical state specificity. Both a compact setup (mini-TIMER) and a separate instrument (EIS-TIMER) dedicated to four-wave-mixing (FWM) experiments has been designed and constructed, to be operated as a branch of the Elastic and Inelastic Scattering beamline: EIS. The FWM experiments that are planned at EIS-TIMER are based on the transient grating approach, where two crossed FEL pulses create a controlled modulation of the sample excitations while a third time-delayed pulse is used to monitor the dynamics of the excited state. This manuscript describes such experimental facilities, showing the preliminary results of the commissioning of the EIS-TIMER beamline, and discusses original experimental strategies being developed to study the dynamics of matter at the fs–nm time–length scales. In the near future such experimental tools will allow more sophisticated FEL-based FWM applications, that also include the use of multiple and multi-color FEL pulses.


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