scholarly journals Evolutionary Dynamics of Indels in SARS-CoV-2 Spike Glycoprotein

2021 ◽  
Vol 17 ◽  
pp. 117693432110646
Author(s):  
R Shyama Prasad Rao ◽  
Nagib Ahsan ◽  
Chunhui Xu ◽  
Lingtao Su ◽  
Jacob Verburgt ◽  
...  
Keyword(s):  
High Frequency ◽  
Selection Pressure ◽  
Evolutionary Dynamics ◽  
Point Mutations ◽  
Selective Advantage ◽  
Fine Tuning ◽  
Spike Glycoprotein ◽  
Enveloped Viruses ◽  
Glycosylation Sites ◽  
Over Time

SARS-CoV-2, responsible for the current COVID-19 pandemic that claimed over 5.0 million lives, belongs to a class of enveloped viruses that undergo quick evolutionary adjustments under selection pressure. Numerous variants have emerged in SARS-CoV-2, posing a serious challenge to the global vaccination effort and COVID-19 management. The evolutionary dynamics of this virus are only beginning to be explored. In this work, we have analysed 1.79 million spike glycoprotein sequences of SARS-CoV-2 and found that the virus is fine-tuning the spike with numerous amino acid insertions and deletions (indels). Indels seem to have a selective advantage as the proportions of sequences with indels steadily increased over time, currently at over 89%, with similar trends across countries/variants. There were as many as 420 unique indel positions and 447 unique combinations of indels. Despite their high frequency, indels resulted in only minimal alteration of N-glycosylation sites, including both gain and loss. As indels and point mutations are positively correlated and sequences with indels have significantly more point mutations, they have implications in the evolutionary dynamics of the SARS-CoV-2 spike glycoprotein.

scholarly journals Evolutionary dynamics of indels in SARS-CoV-2 spike glycoprotein

2021 ◽  
Author(s):  
R. Shyama Prasad Rao ◽  
Nagib Ahsan ◽  
Chunhui Xu ◽  
Lingtao Su ◽  
Jacob Verburgt ◽  
...  
Keyword(s):  
High Frequency ◽  
Selection Pressure ◽  
Evolutionary Dynamics ◽  
Point Mutations ◽  
Selective Advantage ◽  
Fine Tuning ◽  
Spike Glycoprotein ◽  
Enveloped Viruses ◽  
Glycosylation Sites ◽  
Over Time

SARS-CoV-2, responsible for the current COVID-19 pandemic that claimed over 4.2 million lives, belongs to a class of enveloped viruses that undergo quick evolutionary adjustments under selection pressure. Numerous variants have emerged in SARS-CoV-2 that are currently posing a serious challenge to the global vaccination effort and COVID-19 management. The evolutionary dynamics of this virus are only beginning to be explored. In this work, we have analysed 1.79 million spike glycoprotein sequences of SARS-CoV-2 and found that the virus is fine-tuning the spike with numerous amino acid insertions and deletions (indels). Indels seem to have a selective advantage as the proportions of sequences with indels were steadily increasing over time, currently at over 89%, with similar trends across countries/variants. There were as many as 420 unique indel positions and 447 unique combinations of indels. Despite their high frequency, indels resulted in only minimal alteration, including both gain and loss, of N-glycosylation sites. As indels and point mutations are positively correlated and sequences with indels have significantly more point mutations, they have implications in the context of evolutionary dynamics of the SARS-CoV-2 spike glycoprotein.

scholarly journals Extending the Coding Potential of Viral Genomes with Overlapping Antisense ORFs: A Case for the De Novo Creation of the Gene Encoding the Antisense Protein ASP of HIV-1

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 146
Author(s):  
Angelo Pavesi ◽  
Fabio Romerio
Keyword(s):  
De Novo ◽  
Point Mutations ◽  
Selective Advantage ◽  
Genomic Region ◽  
Fine Tuning ◽  
Sequence Evolution ◽  
Viral Genomes ◽  
Stop Codons ◽  
Hiv 1

Gene overprinting occurs when point mutations within a genomic region with an existing coding sequence create a new one in another reading frame. This process is quite frequent in viral genomes either to maximize the amount of information that they encode or in response to strong selective pressure. The most frequent scenario involves two different reading frames in the same DNA strand (sense overlap). Much less frequent are cases of overlapping genes that are encoded on opposite DNA strands (antisense overlap). One such example is the antisense ORF, asp in the minus strand of the HIV-1 genome overlapping the env gene. The asp gene is highly conserved in pandemic HIV-1 strains of group M, and it is absent in non-pandemic HIV-1 groups, HIV-2, and lentiviruses infecting non-human primates, suggesting that the ~190-amino acid protein that is expressed from this gene (ASP) may play a role in virus spread. While the function of ASP in the virus life cycle remains to be elucidated, mounting evidence from several research groups indicates that ASP is expressed in vivo. There are two alternative hypotheses that could be envisioned to explain the origin of the asp ORF. On one hand, asp may have originally been present in the ancestor of contemporary lentiviruses, and subsequently lost in all descendants except for most HIV-1 strains of group M due to selective advantage. Alternatively, the asp ORF may have originated very recently with the emergence of group M HIV-1 strains from SIVcpz. Here, we used a combination of computational and statistical approaches to study the genomic region of env in primate lentiviruses to shed light on the origin, structure, and sequence evolution of the asp ORF. The results emerging from our studies support the hypothesis of a recent de novo addition of the antisense ORF to the HIV-1 genome through a process that entailed progressive removal of existing internal stop codons from SIV strains to HIV-1 strains of group M, and fine tuning of the codon sequence in env that reduced the chances of new stop codons occurring in asp. Altogether, the study supports the notion that the HIV-1 asp gene encodes an accessory protein, providing a selective advantage to the virus.

scholarly journals N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain Are Required for Efficient Viral Incorporation and Replication

2020 ◽  
Vol 94 (19) ◽  
Author(s):  
Henrik Östbye ◽  
Jin Gao ◽  
Mira Rakic Martinez ◽  
Hao Wang ◽  
Jan-Willem de Gier ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Surface Antigen ◽  
Influenza A ◽  
Surface Antigens ◽  
Secretory Protein ◽  
Enveloped Viruses ◽  
Virion Incorporation ◽  
Head Domain ◽  
Glycosylation Sites ◽  
Over Time

ABSTRACT N-linked glycans commonly contribute to secretory protein folding, sorting, and signaling. For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N). Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs. Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin. In contrast, variable sites exist in H3N2 IAVs of human and swine origin, where the number of head glycosylation sites has mainly increased over time. Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs. It also revealed that N1 stability is more affected by the head domain glycans, suggesting N2 is more amenable to glycan additions. Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions. IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen. In addition to promoting secretory protein maturation, enveloped viruses also utilize these large oligosaccharide structures to prevent access to surface antigen epitopes. Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability. Experimental analyses verified that the N-linked glycosylation sites on the NA head domain contribute to virion incorporation and replication. It also revealed that the head domain glycans affect N1 stability more than N2, suggesting N2 is more accommodating to glycan additions. These results demonstrate that in addition to antigenicity, changes in N-linked glycosylation sites can alter other properties of viral surface antigens and virions.

scholarly journals Comparative Analysis Based on the Spike Glycoproteins of SARS-CoV2 Isolated from COVID 19 Patients of Different Countries

2020 ◽  
Author(s):  
Preeti Mangar ◽  
Smriti Pradhan ◽  
Subecha Rai ◽  
Khusboo Lepcha ◽  
Vivek Kumar Ranjan ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Point Mutations ◽  
World Health Organisation ◽  
World Health ◽  
Structural Proteins ◽  
Spike Glycoprotein ◽  
The World ◽  
Transmittance Factor ◽  
Over Time

SARS-CoV2 popularly known as (COVID-19) has presently received worldwide attention. It has been considered a pandemic by the World Health Organisation. Owing to its high transmittance factor the virus has brought about many deaths and spread to all the major countries of the world. Scientists and Researchers worldwide are giving their full efforts to develop a vaccine. In our present study, we have included the comparative analysis of the different spike glycoprotein sequences of the patients suffering from COVID-19 from different countries where this pandemic has occurred. Spike glycoproteins are the structural proteins that bring about the binding of the SARS-CoV-2 viral molecule to the ACE2 receptor of the host following which infection occurs. Through this data, we have shown the different point mutations in the spike glycoproteins that occurred over time in different countries as the disease progressed.

scholarly journals N-linked glycan sites on the influenza NA head domain are required for efficient IAV incorporation and replication

2020 ◽  
Author(s):  
Henrik Östbye ◽  
Jin Gao ◽  
Mira Rakic Martinez ◽  
Hao Wang ◽  
Jan-Willem de Gier ◽  
...  
Keyword(s):  
Influenza A ◽  
Surface Antigens ◽  
Secretory Protein ◽  
Human Origin ◽  
Time Analysis ◽  
Enveloped Viruses ◽  
Virion Incorporation ◽  
Head Domain ◽  
Glycosylation Sites ◽  
Over Time

ABSTRACTN-linked glycans commonly contribute to secretory protein folding, sorting and signaling. For enveloped viruses such as the influenza A virus (IAV), the addition of large N-linked glycans can also prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N). Sequence analysis showed that in the NA head domain of H1N1 IAVs three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs. Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased and then decreased over time. In contrast, variable sites exist in H3N2 IAVs of human and swine origin, where the number of head glycosylation sites has mainly increased over time. Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells or eggs. It also revealed that N1 stability is more affected by the head domain glycans, suggesting N2 is more amenable to glycan additions. Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.

Role of key point Mutations in Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein

2020 ◽  
Vol 20 ◽  
Author(s):  
Bipin Singh
Keyword(s):  
Receptor Binding ◽  
Point Mutations ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Angiotensin Converting Enzyme 2 ◽  
Recent Outbreak ◽  
Novel Coronavirus ◽  
Genomic Similarity

: The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its worldwide spread is posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARSCoV based on the comparison of the genome sequence. Despite the genomic similarity between SARS-CoV-2 and SARSCoV, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows the considerable difference compared to SARS-CoV, due to the presence of several point mutations. The analysis of receptor binding domain (RBD) from recently published 3D structures of spike glycoprotein of SARS-CoV-2 (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)) highlights the contribution of a few key point mutations in RBD of spike glycoprotein and molecular basis of its efficient binding with human angiotensin-converting enzyme 2 (ACE2).

scholarly journals Sequence Variation and Haplotype Structure at the HumanHFELocus

Genetics ◽  
2002 ◽  
Vol 161 (4) ◽  
pp. 1609-1623 ◽  
Author(s):  
Christopher Toomajian ◽  
Martin Kreitman
Keyword(s):  
High Frequency ◽  
Nucleotide Diversity ◽  
Sequence Variation ◽  
Hla Class I ◽  
Selective Advantage ◽  
European Ancestry ◽  
Iron Regulation ◽  
Intragenic Recombination ◽  
Nucleotide Variability ◽  
Show Evidence

AbstractThe HFE locus encodes an HLA class-I-type protein important in iron regulation and segregates replacement mutations that give rise to the most common form of genetic hemochromatosis. The high frequency of one disease-associated mutation, C282Y, and the nature of this disease have led some to suggest a selective advantage for this mutation. To investigate the context in which this mutation arose and gain a better understanding of HFE genetic variation, we surveyed nucleotide variability in 11.2 kb encompassing the HFE locus and experimentally determined haplotypes. We fully resequenced 60 chromosomes of African, Asian, or European ancestry as well as one chimpanzee, revealing 41 variable sites and a nucleotide diversity of 0.08%. This indicates that linkage to the HLA region has not substantially increased the level of HFE variation. Although several haplotypes are shared between populations, one haplotype predominates in Asia but is nearly absent elsewhere, causing higher than average genetic differentiation among the three major populations. Our samples show evidence of intragenic recombination, so the scarcity of recombination events within the C282Y allele class is consistent with selection increasing the frequency of a young allele. Otherwise, the pattern of variability in this region does not clearly indicate the action of positive selection at this or linked loci.

scholarly journals Environmental changes dictate selection and nonspecific epistasis in an empirical phenotype-environment-fitness landscape

2021 ◽  
Author(s):  
J.Z. Chen ◽  
D.M. Fowler ◽  
N. Tokuriki
Keyword(s):  
Selection Pressure ◽  
Evolutionary Dynamics ◽  
Environmental Changes ◽  
Fitness Landscape ◽  
Resistance Level ◽  
Phenotypic Changes ◽  
Environmental Selection ◽  
Selection Environment ◽  
Data Points ◽  
Environmental Dependence

SummaryThe fitness landscape, a function that maps genotypic and phenotypic changes to their effects on fitness, is an invaluable concept in evolutionary biochemistry. Though widely discussed, measurements of phenotype-fitness landscapes in proteins remain scarce. Here, we quantify all single mutational effects on fitness and phenotype (antibiotic resistance level) of VIM-2 β-lactamase (5600 variants) across a 64-fold range of ampicillin concentrations by deep mutational scanning. We then construct a phenotype-fitness landscape that takes variations in environmental selection pressure into account (a phenotype-environment-fitness landscape). We found that a simple, empirical landscape accurately models the ~39,000 mutational data points, which suggests the evolution of VIM-2 can be predicted based on the selection environment. Our landscape provides new quantitative knowledge on the evolution of the β-lactamases and proteins in general, particularly their evolutionary dynamics under sub-inhibitory antibiotic concentrations, as well as the mechanisms and environmental dependence of nonspecific epistasis.

scholarly journals Seed Banks Alter the Rate and Direction of Molecular Evolution in Bacillus subtilis

2021 ◽  
Author(s):  
William R. Shoemaker ◽  
Evgeniya Polezhaeva ◽  
Kenzie B. Givens ◽  
Jay T. Lennon
Keyword(s):  
Bacillus Subtilis ◽  
Molecular Evolution ◽  
Seed Bank ◽  
Negative Selection ◽  
Evolutionary Dynamics ◽  
Genetic Manipulation ◽  
Seed Banks ◽  
Rate Of Molecular Evolution ◽  
Over Time ◽  
Growth And Reproduction

Fluctuations in the availability of resources constrains the growth and reproduction of individuals, which in turn effects the evolution of their respective populations. Many organisms are able to respond to fluctuations by entering a reversible state of reduced metabolic activity, a phenomenon known as dormancy. This pool of dormant individuals (i.e., a seed bank) does not reproduce and is expected to act as an evolutionary buffer, though it is difficult to observe this effect directly over an extended evolutionary timescale. Through genetic manipulation, we analyze the molecular evolutionary dynamics of Bacillus subtilis populations in the presence and absence of a seed bank over 700 days. We find that the ability to enter a dormant state increases the accumulation of genetic diversity over time and alters the trajectory of mutations, findings that are recapitulated using simulations based on a simple mathematical model. While the ability to form a seed bank does not alter the degree of negative selection, we find that it consistently alters the direction of molecular evolution across genes. Together, these results show that the ability to form a seed bank affects the direction and rate of molecular evolution over an extended evolutionary timescale.

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