scholarly journals Neutral evolution test of the spike protein of SARS-CoV-2 and its implications in the binding to ACE2

2021 ◽  
Author(s):  
Georgina I. López-Cortés ◽  
Miryam Palacios-Pérez ◽  
Gabriel S. Zamudio ◽  
Hannya F. Veledíaz ◽  
Enrique Ortega ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Neutral Theory ◽  
Purifying Selection ◽  
Spike Protein ◽  
Health Concern ◽  
Neutral Evolution ◽  
Occurrence Rate ◽  
Evolutionary Mechanisms ◽  
Evolutionary Forces ◽  
Selective Pressures

Abstract As the SARS-CoV-2 has spread and the pandemic has dragged on, the virus continued to evolve rapidly resulting in the emergence of new highly transmissible variants that can be of public health concern. The evolutionary mechanisms that drove this rapid diversity are not well understood but neutral evolution should open the first insight. The neutral theory of evolution states that most mutations in the nucleic acid sequences are random and they can be fixed or disappear by purifying selection. Herein, we performed a neutrality test to better understand the selective pressures exerted over SARS-CoV-2 Spike protein, as well as in four of the identified health concern variants. Lys and Thr have higher occurrence rate on the Receptor Binding Domain (RBD) than in the overall sequence whereas Cys, His, and importantly Arg have low occurrence rate both in the whole protein and the RBD. Amino acids that have lower occurrence than the expected neutral control influence in the stability and or functionality of the protein. Our results show that most unique mutations either for SARS-CoV-2 or the variants of health concern are under selective pressures, which could be related either to the evasion of the immune system, increasing the virus’ fitness or altering protein – protein interactions with host proteins. Altogether all these forces have shaped the Spike protein. Understanding the evolutionary forces that act upon Spike protein may help designing better treatments and vaccines that target variants of health concern.

scholarly journals Neutral evolution test of the spike protein of SARS-CoV-2 and its implications in the binding to ACE2

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Georgina I. López-Cortés ◽  
Miryam Palacios-Pérez ◽  
Gabriel S. Zamudio ◽  
Hannya F. Veledíaz ◽  
Enrique Ortega ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Neutral Theory ◽  
Purifying Selection ◽  
Spike Protein ◽  
Health Concern ◽  
Neutral Evolution ◽  
Evolutionary Mechanisms ◽  
Theory Of Evolution ◽  
Selective Pressures

AbstractAs the SARS-CoV-2 has spread and the pandemic has dragged on, the virus continued to evolve rapidly resulting in the emergence of new highly transmissible variants that can be of public health concern. The evolutionary mechanisms that drove this rapid diversity are not well understood but neutral evolution should open the first insight. The neutral theory of evolution states that most mutations in the nucleic acid sequences are random and they can be fixed or disappear by purifying selection. Herein, we performed a neutrality test to better understand the selective pressures exerted over SARS-CoV-2 spike protein from homologue proteins of Betacoronavirus, as well as to the spikes from human clinical isolates of the virus. Specifically, Tyr and Asn have higher occurrence rates on the Receptor Binding Domain (RBD) and in the overall sequence of spike proteins of Betacoronavirus, whereas His and Arg have lower occurrence rates. The in vivo evolutionary phenomenon of SARS-CoV-2 shows that Glu, Lys, Phe, and Val have the highest probability of occurrence in the emergent viral particles. Amino acids that have higher occurrence than the expected by the neutral control, are favorable and are fixed in the sequence while the ones that have lower occurrence than expected, influence the stability and/or functionality of the protein. Our results show that most unique mutations either for SARS-CoV-2 or its variants of health concern are under selective pressures, which could be related either to the evasion of the immune system, increasing the virus’ fitness or altering protein – protein interactions with host proteins. We explored the consequences of those selected mutations in the structure and protein – protein interaction with the receptor. Altogether all these forces have shaped the spike protein and the continually evolving variants.

scholarly journals Therapeutic development by repurposing drugs targeting SARS-CoV-2 spike protein interactions by simulation studies

2021 ◽  
Author(s):  
Qazi Mohammad Sajid Jamal ◽  
Varish Ahmad ◽  
Ali H Alharbi ◽  
Mohammad Azam Ansari ◽  
Mohammad A Alzohairy ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Spike Protein ◽  
Simulation Studies ◽  
Therapeutic Development

scholarly journals Diversity and evolution of surface polysaccharide synthesis loci in Enterobacteriales

2019 ◽  
Author(s):  
Kathryn E. Holt ◽  
Florent Lassalle ◽  
Kelly L. Wyres ◽  
Ryan Wick ◽  
Rafal J. Mostowy
Keyword(s):  
Evolutionary Dynamics ◽  
Bacterial Species ◽  
Purifying Selection ◽  
Evolutionary Forces ◽  
Polysaccharide Synthesis ◽  
Surface Polysaccharides ◽  
Surface Polysaccharide ◽  
Selective Preservation ◽  
Multiple Species

Bacterial capsules and lipopolysaccharides are diverse surface polysaccharides (SPs) that serve as the frontline for interactions with the outside world. While SPs can evolve rapidly, their diversity and evolutionary dynamics across different taxonomic scales has not been investigated in detail. Here, we focused on the bacterial order Enterobacteriales (including the medically-relevant Enterobacteriaceae), to carry out comparative genomics of two SP locus synthesis regions, cps and kps, using 27,334 genomes from 45 genera. We identified high-quality cps loci in 22 genera and kps in 11 genera, around 4% of which were detected in multiple species. We found SP loci to be highly dynamic genetic entities: their evolution was driven by high rates of horizontal gene transfer (HGT), both of whole loci and component genes, and relaxed purifying selection, yielding large repertoires of SP diversity. In spite of that, we found the presence of (near-)identical locus structures in distant taxonomic backgrounds that could not be explained by recent exchange, pointing to long-term selective preservation of locus structures in some populations. Our results reveal differences in evolutionary dynamics driving SP diversity within different bacterial species, with lineages of Escherichia coli, Enterobacter hormachei and Klebsiella aerogenes most likely to share SP loci via recent exchange; and lineages of Salmonella enterica, Citrobacter sakazakii and Serratia marcescens most likely to share SP loci via other mechanisms such as long-term preservation. Overall, the evolution of SP loci in Enterobacteriales is driven by a range of evolutionary forces and their dynamics and relative importance varies between different species.

scholarly journals Divergent and convergent evolution of housekeeping genes in human–pig lineage

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4840 ◽  
Author(s):  
Kai Wei ◽  
Tingting Zhang ◽  
Lei Ma
Keyword(s):  
Active Sites ◽  
Evolutionary Dynamics ◽  
Purifying Selection ◽  
Housekeeping Genes ◽  
Neutral Evolution ◽  
Structure Evolution ◽  
Tissue Cell ◽  
Sequencing Data ◽  
Cellular Functions ◽  
Species Specific

Housekeeping genes are ubiquitously expressed and maintain basic cellular functions across tissue/cell type conditions. The present study aimed to develop a set of pig housekeeping genes and compare the structure, evolution and function of housekeeping genes in the human–pig lineage. By using RNA sequencing data, we identified 3,136 pig housekeeping genes. Compared with human housekeeping genes, we found that pig housekeeping genes were longer and subjected to slightly weaker purifying selection pressure and faster neutral evolution. Common housekeeping genes, shared by the two species, achieve stronger purifying selection than species-specific genes. However, pig- and human-specific housekeeping genes have similar functions. Some species-specific housekeeping genes have evolved independently to form similar protein active sites or structure, such as the classical catalytic serine–histidine–aspartate triad, implying that they have converged for maintaining the basic cellular function, which allows them to adapt to the environment. Human and pig housekeeping genes have varied structures and gene lists, but they have converged to maintain basic cellular functions essential for the existence of a cell, regardless of its specific role in the species. The results of our study shed light on the evolutionary dynamics of housekeeping genes.

scholarly journals Purifying selection of CCR5-tropic human immunodeficiency virus type 1 variants in AIDS subjects that have developed syncytium-inducing, CXCR4-tropic viruses

2006 ◽  
Vol 87 (5) ◽  
pp. 1285-1294 ◽  
Author(s):  
Guerau Fernàndez ◽  
Anuska Llano ◽  
Miriam Esgleas ◽  
Bonaventura Clotet ◽  
José A. Esté ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Purifying Selection ◽  
Selective Pressures ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Hiv 1

Human immunodeficiency virus type 1 (HIV-1) infection is established by virus variants that use the CCR5 co-receptor for entry (CCR5-tropic or R5 variants), whereas viruses that use CXCR4 as co-receptor (CXCR4-tropic or X4 variants) emerge during disease progression in approximately 50 % of infected subjects. X4 variants may have a higher fitness ex vivo and their detection is usually accompanied by faster T-cell depletion and the onset of AIDS in HIV-1-positive individuals. Here, the relationship between the sequence variation of the HIV-1 env V3–V5 region and positive selective pressure on R5 and X4 variants from infected subjects with CD4 T cell counts below 200 cells μl−1 was studied. A correlation was found between genetic distance and CD4+ cell count at late stages of the disease. R5 variants that co-existed with X4 variants were significantly less heterogeneous than R5 variants from subjects without X4 variants (P<0·0001). Similarly, X4 variants had a significantly higher diversity than R5 variants (P<0·0001), although residues under positive selection had a similar distribution pattern in both variants. Therefore, both X4 and R5 variants were subjected to high selective pressures from the host. Furthermore, the interaction between X4 and R5 variants within the same subject resulted in a purifying selection on R5 variants, which only survived as a homogeneous virus population. These results indicate that R5 variants from X4 phenotype samples were highly homogeneous and under weakly positive selective pressures. In contrast, R5 variants from R5 phenotype samples were highly heterogeneous and subject to positive selective pressures.

Combinatorics of Genotype-Phenotype Maps: An RNA Case Study

2005 ◽  
Author(s):  
Christian M. Reidys
Keyword(s):  
Natural Selection ◽  
Genetic Drift ◽  
Optimization Problem ◽  
Neutral Theory ◽  
Biological Evolution ◽  
Neutral Evolution ◽  
Evolutionary Search ◽  
Random Drift ◽  
Molecular Change ◽  
Biological Phenomena

The fundamental mechanisms of biological evolution have fascinated generations of researchers and remain popular to this day. The formulation of such a theory goes back to Darwin (1859), who in the The Origin of Species presented two fundamental principles: genetic variability caused by mutation, and natural selection. The first principle leads to diversity and the second one to the concept of survival of the fittest, where fitness is an inherited characteristic property of an individual and can basically be identified with its reproduction rate. Wright [530, 531] first recognized the importance of genetic drift in evolution in improving the evolutionary search capacity of the whole population. He viewed genetic drift merely as a process that could improve evolutionary search. About a decade later, Kimura proposed [317] that the majority of changes that are observed in evolution at the molecular level are the results of random drift of genotypes. The neutral theory of Kimura does not deny that selection plays a role, but claims that no appreciable fraction of observable molecular change can be caused by selective forces: mutations are either a disadvantage or, at best, neutral in present day organisms. Only negative selection plays a major role in the neutral evolution, in that deleterious mutants die out due to their lower fitness. Over the last few decades, there has been a shift of emphasis in the study of evolution. Instead of focusing on the differences in the selective value of mutants and on population genetics, interest has moved to evolution through natural selection as an abstract optimization problem. Given the tremendous opportunities that computer science and the physical sciences now have for contributing to the study of biological phenomena, it is fitting to study the evolutionary optimization problem in the present volume. In this chapter, we adopt the following framework: assuming that selection acts exclusively upon isolated phenotypes, we introduce the following compositum of mappings . . . Genotypes→ Phenotypes →Fitness . . . . We will refer to the first map as to the genotype-phenotype map and call the preimage of a given phenotype its neutral network. Clearly, the main ingredients here are the phenotypes and genotypes and their respective organization. In the following we will study various combinatorial properties of phenotypes and genotypes for RNA folding maps.

Exchanging fluids

2020 ◽  
Vol 39 (1) ◽  
pp. 56-86
Author(s):  
Tomás Cabeza de Baca ◽  
Aurelio José Figueredo ◽  
Heitor Fernandes ◽  
Vanessa Smith-Castro
Keyword(s):  
Latin America ◽  
Cultural Landscape ◽  
Population Level ◽  
Cultural Changes ◽  
Evolutionary Mechanisms ◽  
Evolutionary Forces ◽  
European Colonization ◽  
The Caribbean ◽  
Human Mating ◽  
Sociocultural Interactions

AbstractKnowledge of evolutionary influences on patterns of human mating, social interactions, and differential health is increasing, yet these insights have rarely been applied to historical analyses of human population dynamics. The genetic and evolutionary forces behind biases in interethnic mating and in the health of individuals of different ethnic groups in Latin America and the Caribbean since the European colonization of America are still largely ignored. We discuss how historical and contemporary sociocultural interactions and practices are strongly influenced by population-level evolutionary forces. Specifically, we discuss the historical implications of functional (de facto) polygyny, sex-biased admixture, and assortative mating in Latin America. We propose that these three evolutionary mechanisms influenced mating patterns, shaping the genetic and cultural landscape across Latin America and the Caribbean. Further, we discuss how genetic differences between the original populations that migrated at different times into Latin America contributed to their accommodation to and survival in the different local ecologies and interethnic interactions. Relevant medical and social implications follow from the genetic and cultural changes reviewed.

scholarly journals Peptide-Protein Interaction Studies of Antimicrobial Peptides Targeting Middle East Respiratory Syndrome Coronavirus Spike Protein: An In Silico Approach

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Sabeena Mustafa ◽  
Hanan Balkhy ◽  
Musa Gabere
Keyword(s):  
Middle East ◽  
Antimicrobial Peptides ◽  
Protein Interactions ◽  
In Silico ◽  
Therapeutic Option ◽  
Binding Mode ◽  
Middle East Respiratory Syndrome ◽  
Spike Protein ◽  
In Silico Docking ◽  
Peptide Database

There is no effective therapeutic or vaccine for Middle East Respiratory Syndrome and this study attempts to find therapy using peptide by establishing a basis for the peptide-protein interactions through in silico docking studies for the spike protein of MERS-CoV. The antimicrobial peptides (AMPs) were retrieved from the antimicrobial peptide database (APD3) and shortlisted based on certain important physicochemical properties. The binding mode of the shortlisted peptides was measured based on the number of clusters which forms in a protein-peptide docking using Piper. As a result, we identified a list of putative AMPs which binds to the spike protein of MERS-CoV, which may be crucial in providing the inhibitory action. It is observed that seven putative peptides have good binding score based on cluster size cutoff of 208. We conclude that seven peptides, namely, AP00225, AP00180, AP00549, AP00744, AP00729, AP00764, and AP00223, could possibly have binding with the active site of the MERS-CoV spike protein. These seven AMPs could serve as a therapeutic option for MERS and enhance its treatment outcome.

scholarly journals Molecular Genetic Analysis of Cucumber mosaic virus Populations Infecting Pepper Suggests Unique Patterns of Evolution in Korea

2014 ◽  
Vol 104 (9) ◽  
pp. 993-1000 ◽  
Author(s):  
Mi-Kyeong Kim ◽  
Jang-Kyun Seo ◽  
Hae-Ryun Kwak ◽  
Jeong-Soo Kim ◽  
Kook-Hyung Kim ◽  
...  
Keyword(s):  
Genetic Structure ◽  
Cucumber Mosaic Virus ◽  
Mosaic Virus ◽  
Molecular Genetic ◽  
Purifying Selection ◽  
Molecular Genetic Analysis ◽  
Full Genome Sequence ◽  
Full Genome ◽  
Full Genome Sequencing ◽  
Evolutionary Mechanisms

Studying genetic structure and diversity of viruses is important to understand the evolutionary mechanisms that generate and maintain variations in viral populations. Cucumber mosaic virus (CMV) is endemic in most pepper fields in Korea. Currently, no effective methods for control of CMV are available due to many environmental and biological factors such as the extensive evolutionary capacity of CMV. Thus, analyzing the genetic structure of CMV populations may facilitate the development of strategies for the control of CMV. In this study, 252 pepper (Capsicum annuum) samples showing virus symptoms were collected by field surveys performed throughout Korea in 2007. Reverse-transcription polymerase chain reaction analyses revealed that, in total, 165 collected samples were infected with CMV. Forty-five CMV isolates were randomly selected within each regional subpopulation and analyzed by full-genome sequencing. Analyses of genetic diversity showed that the 2b gene of CMV is under weaker purifying selection than the other genes. Based on the phylogenetic analysis of RNA1, the CMV isolates from pepper were divided into three clusters in subgroup I. Our full-genome sequence-based molecular analyses of the CMV Korean population suggest that the subpopulations of CMV have been geographically localized in pepper fields in Korea.

scholarly journals Evaluating the Impact of Purifying Selection on Species-level Molecular Dating

2019 ◽  
Author(s):  
Chong He ◽  
Dan Liang ◽  
Peng Zhang
Keyword(s):  
Molecular Clock ◽  
Neutral Theory ◽  
Purifying Selection ◽  
Selective Constraint ◽  
Species Level ◽  
Molecular Dating ◽  
Substitution Saturation ◽  
Time Estimates ◽  
Branch Lengths ◽  
The Impact

AbstractThe neutral theory of molecular evolution suggests that the constancy of the molecular clock relies on the neutral condition. Thus, purifying selection, the most common type of natural selection, could influence the constancy of the molecular clock, and the use of genes/sites under purifying selection may produce less reliable molecular dating results. However, in current practices of species-level molecular dating, some researchers prefer to select slowly evolving genes/sites to avoid the potential impact of substitution saturation. These genes/sites are generally under a strong influence of purifying selection. Here, from the data of 23 published mammal genomes, we constructed datasets under various selective constraints. We compared the differences in branch lengths and time estimates among these datasets to investigate the impact of purifying selection on species-level molecular dating. We found that as the selective constraint increases, terminal branches are extended, which introduces biases into the result of species-level molecular dating. This result suggests that in species-level molecular dating, the impact of purifying selection should be taken into consideration, and researchers should be more cautious with the use of genes/sites under purifying selection.

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