Evolutionary Profile for (Host and Viral) MLKL Indicates Its Activities as a Battlefront for Extensive Counteradaptation

Abstract Pathogen infection triggers host innate defenses which may result in the activation of regulated cell death (RCD) pathways such as apoptosis. Given a vital role in immunity, apoptotic effectors are often counteracted by pathogen-encoded antagonists. Mounting evidence indicates that programmed necrosis, which is mediated by the RIPK3/MLKL axis and termed necroptosis, evolved as a countermeasure to pathogen-mediated inhibition of apoptosis. Yet, it is unclear whether components of this emerging RCD pathway display signatures associated with pathogen conflict that are rare in combination but common to key host defense factors, namely, rapid evolution, viral homolog (virolog), and cytokine induction. We leveraged evolutionary sequence analysis that examines rates of amino acid replacement, which revealed: 1) strong and recurrent signatures of positive selection for primate and bat RIPK3 and MLKL, and 2) elevated rates of amino acid substitution on multiple RIPK3/MLKL surfaces suggestive of past antagonism with multiple, distinct pathogen-encoded inhibitors. Furthermore, our phylogenomics analysis across poxvirus genomes illuminated volatile patterns of evolution for a recently described MLKL viral homolog. Specifically, poxviral MLKLs have undergone numerous gene replacements mediated by duplication and deletion events. In addition, MLKL protein expression is stimulated by interferons in human and mouse cells. Thus, MLKL displays all three hallmarks of pivotal immune factors of which only a handful of factors like OAS1 exhibit. These data support the hypothesis that over evolutionary time MLKL functions—which may include execution of necroptosis—have served as a major determinant of infection outcomes despite gene loss in some host genomes.

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An extension of Wang protein design model using Blosum62 substitution matrix

10.1101/2021.06.07.447415 ◽

2021 ◽

Author(s):

Amin Rahmani ◽

Fatemeh Zare-Mirakabad

Keyword(s):

Protein Structure ◽

Amino Acid ◽

Protein Design ◽

Tertiary Structure ◽

Amino Acid Replacement ◽

Vital Role ◽

The Body ◽

Substitution Matrix ◽

Evolutionary Information ◽

Deep Learning Model

Humans life depends on the functionality of molecules in the body. One of these essential molecules is the protein that plays a vital role in our life, such that its malfunction can cause severe damages. Such roles make protein structure and its functionality necessary to understand. One of the problems that help us understand the relation between protein structure is the well-known protein design problem which attempts to find an amino acid sequence that can fold into a desired tertiary structure. However, despite having an acceptable accuracy in protein design, this accuracy is an identical percentage of amino acid retrieving. At the same time, it is well-known that amino acids can replace each other in evolution while the function and structure of protein stay the same. Thus the designed sequence does not have the opportunity to be close to the target in the evolutionary aspect. This paper presents an extension to Wang's deep learning model, which uses evolutionary information in the Blosum62 substitution matrix to take amino acid replacement probability into account while designing a sequence.

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Some Structural Features of Metaphase Chromosomes of Mice and Men

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100060969 ◽

1967 ◽

Vol 25 ◽

pp. 190-191

Author(s):

Godfrey C. Hoskins ◽

Betty B. Hoskins

Keyword(s):

Electron Microscopy ◽

Electron Micrographs ◽

Structural Features ◽

Metaphase Chromosomes ◽

The Future ◽

Of Mice And Men ◽

Mouse Cells ◽

Human And Mouse

Metaphase chromosomes from human and mouse cells in vitro are isolated by micrurgy, fixed, and placed on grids for electron microscopy. Interpretations of electron micrographs by current methods indicate the following structural features.Chromosomal spindle fibrils about 200Å thick form fascicles about 600Å thick, wrapped by dense spiraling fibrils (DSF) less than 100Å thick as they near the kinomere. Such a fascicle joins the future daughter kinomere of each metaphase chromatid with those of adjacent non-homologous chromatids to either side. Thus, four fascicles (SF, 1-4) attach to each metaphase kinomere (K). It is thought that fascicles extend from the kinomere poleward, fray out to let chromosomal fibrils act as traction fibrils against polar fibrils, then regroup to join the adjacent kinomere.

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A Novel Polymorphism in Exon 10 of the Factor V Gene Inducing an Amino Acid Replacement of Arginine to Lysine at Codon 485

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665424 ◽

1997 ◽

Vol 78 (05) ◽

pp. 1419-1420 ◽

Cited By ~ 1

Author(s):

Tetsuo Ozawa ◽

Kenji Niiya ◽

Naoko Ejiri ◽

Nobuo Sakuragawa

Keyword(s):

Amino Acid ◽

Amino Acid Replacement ◽

Factor V ◽

Factor V Gene ◽

V Gene ◽

Exon 10

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Assessing the Impact of Secondary Structure and Solvent Accessibility on Protein Evolution

Genetics ◽

10.1093/genetics/149.1.445 ◽

1998 ◽

Vol 149 (1) ◽

pp. 445-458 ◽

Cited By ~ 21

Author(s):

Nick Goldman ◽

Jeffrey L Thorne ◽

David T Jones

Keyword(s):

Amino Acid ◽

Secondary Structure ◽

Protein Evolution ◽

Solvent Accessibility ◽

Strong Association ◽

Length Distribution ◽

Parametric Bootstrap ◽

Amino Acid Replacement ◽

Physical Constraints ◽

The Impact

Abstract Empirically derived models of amino acid replacement are employed to study the association between various physical features of proteins and evolution. The strengths of these associations are statistically evaluated by applying the models of protein evolution to 11 diverse sets of protein sequences. Parametric bootstrap tests indicate that the solvent accessibility status of a site has a particularly strong association with the process of amino acid replacement that it experiences. Significant association between secondary structure environment and the amino acid replacement process is also observed. Careful description of the length distribution of secondary structure elements and of the organization of secondary structure and solvent accessibility along a protein did not always significantly improve the fit of the evolutionary models to the data sets that were analyzed. As indicated by the strength of the association of both solvent accessibility and secondary structure with amino acid replacement, the process of protein evolution—both above and below the species level—will not be well understood until the physical constraints that affect protein evolution are identified and characterized.

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Genetic Variation and Evolution of the 2019 Novel Coronavirus

Public Health Genomics ◽

10.1159/000513530 ◽

2021 ◽

pp. 1-13

Author(s):

Salvatore Dimonte ◽

Muhammed Babakir-Mina ◽

Taib Hama-Soor ◽

Salar Ali

Keyword(s):

Amino Acid ◽

Receptor Binding ◽

Rapid Evolution ◽

Single Amino Acid ◽

Angiotensin Converting Enzyme 2 ◽

New Type ◽

Amino Acid Mutations ◽

Host Infection ◽

Human Coronaviruses ◽

Novel Coronavirus

Introduction: SARS-CoV-2 is a new type of coronavirus causing a pandemic severe acute respiratory syndrome (SARS-2). Coronaviruses are very diverting genetically and mutate so often periodically. The natural selection of viral mutations may cause host infection selectivity and infectivity. Methods: This study was aimed to indicate the diversity between human and animal coronaviruses through finding the rate of mutation in each of the spike, nucleocapsid, envelope, and membrane proteins. Results: The mutation rate is abundant in all 4 structural proteins. The most number of statistically significant amino acid mutations were found in spike receptor-binding domain (RBD) which may be because it is responsible for a corresponding receptor binding in a broad range of hosts and host selectivity to infect. Among 17 previously known amino acids which are important for binding of spike to angiotensin-converting enzyme 2 (ACE2) receptor, all of them are conservative among human coronaviruses, but only 3 of them significantly are mutated in animal coronaviruses. A single amino acid aspartate-454, that causes dissociation of the RBD of the spike and ACE2, and F486 which gives the strength of binding with ACE2 remain intact in all coronaviruses. Discussion/Conclusion: Observations of this study provided evidence of the genetic diversity and rapid evolution of SARS-CoV-2 as well as other human and animal coronaviruses.

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Evidence for Selection at the fused1 Locus of Drosophila americana

Genetics ◽

10.1093/genetics/158.1.279 ◽

2001 ◽

Vol 158 (1) ◽

pp. 279-290 ◽

Cited By ~ 4

Author(s):

Jorge Vieira ◽

Bryant F McAllister ◽

Brian Charlesworth

Keyword(s):

Amino Acid ◽

Sequence Variation ◽

Amino Acid Replacement ◽

Population Subdivision ◽

Amino Acid Substitutions ◽

Clinal Variation ◽

Haplotype Structure ◽

Common Amino Acid ◽

Chromosome Arrangement ◽

Dna Sequence Variation

Abstract We analyze genetic variation at fused1, a locus that is close to the centromere of the X chromosome-autosome (X/4) fusion in Drosophila americana. In contrast to other X-linked and autosomal genes, for which a lack of population subdivision in D. americana has been observed at the DNA level, we find strong haplotype structure associated with the alternative chromosomal arrangements. There are several derived fixed differences at fused1 (including one amino acid replacement) between two haplotype classes of this locus. From these results, we obtain an estimate of an age of ∼0.61 million years for the origin of the two haplotypes of the fused1 gene. Haplotypes associated with the X/4 fusion have less DNA sequence variation at fused1 than haplotypes associated with the ancestral chromosome arrangement. The X/4 haplotypes also exhibit clinal variation for the allele frequencies of the three most common amino acid replacement polymorphisms, but not for adjacent silent polymorphisms. These patterns of variation are best explained as a result of selection acting on amino acid substitutions, with geographic variation in selection pressures.

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Molecular Analysis of SARS-CoV-2 Genetic Lineages in Jordan: Tracking the Introduction and Spread of COVID-19 UK Variant of Concern at a Country Level

Pathogens ◽

10.3390/pathogens10030302 ◽

2021 ◽

Vol 10 (3) ◽

pp. 302

Author(s):

Malik Sallam ◽

Azmi Mahafzah

Keyword(s):

Amino Acid ◽

Amino Acid Substitution ◽

Rapid Evolution ◽

Molecular Signature ◽

Special Focus ◽

Genetic Lineage ◽

Synonymous Mutation ◽

Spike Gene ◽

Genetic Lineages ◽

The Uk

The rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is manifested by the emergence of an ever-growing pool of genetic lineages. The aim of this study was to analyze the genetic variability of SARS-CoV-2 in Jordan, with a special focus on the UK variant of concern. A total of 579 SARS-CoV-2 sequences collected in Jordan were subjected to maximum likelihood and Bayesian phylogenetic analysis. Genetic lineage assignment was undertaken using the Pango system. Amino acid substitutions were investigated using the Protein Variation Effect Analyzer (PROVEAN) tool. A total of 19 different SARS-CoV-2 genetic lineages were detected, with the most frequent being the first Jordan lineage (B.1.1.312), first detected in August 2020 (n = 424, 73.2%). This was followed by the second Jordan lineage (B.1.36.10), first detected in September 2020 (n = 62, 10.7%), and the UK variant of concern (B.1.1.7; n = 36, 6.2%). In the spike gene region, the molecular signature for B.1.1.312 was the non-synonymous mutation A24432T resulting in a deleterious amino acid substitution (Q957L), while the molecular signature for B.1.36.10 was the synonymous mutation C22444T. Bayesian analysis revealed that the UK variant of concern (B.1.1.7) was introduced into Jordan in late November 2020 (mean estimate); four weeks earlier than its official reporting in the country. In Jordan, an exponential increase in COVID-19 cases due to B.1.1.7 lineage coincided with the new year 2021. The highest proportion of phylogenetic clustering was detected for the B.1.1.7 lineage. The amino acid substitution D614G in the spike glycoprotein was exclusively present in the country from July 2020 onwards. Two Jordanian lineages dominated infections in the country, with continuous introduction/emergence of new lineages. In Jordan, the rapid spread of the UK variant of concern should be monitored closely. The spread of SARS-CoV-2 mutants appeared to be related to the founder effect; nevertheless, the biological impact of certain mutations should be further investigated.

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Identification of critical amino acid residues in human and mouse granulocyte-macrophage colony-stimulating factor and their involvement in species specificity

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)92772-9 ◽

1991 ◽

Vol 266 (21) ◽

pp. 13804-13810 ◽

Cited By ~ 1

Author(s):

A.B. Shanafelt ◽

K.E. Johnson ◽

R.A. Kastelein

Keyword(s):

Amino Acid ◽

Species Specificity ◽

Amino Acid Residues ◽

Colony Stimulating Factor ◽

Critical Amino Acid ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor ◽

Human And Mouse

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Evolution, expression and functional analysis of cultivated allotetraploid cotton DIR genes

BMC Plant Biology ◽

10.1186/s12870-021-02859-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhengwen Liu ◽

Xingfen Wang ◽

Zhengwen Sun ◽

Yan Zhang ◽

Chengsheng Meng ◽

...

Keyword(s):

Gene Family ◽

Stress Responses ◽

Rapid Evolution ◽

Gene Clusters ◽

Vital Role ◽

Fiber Development ◽

Rna Seq ◽

Evolutionarily Conserved ◽

Cell Wall Development ◽

Tandem Duplications

Abstract Background Dirigent (DIR) proteins mediate regioselectivity and stereoselectivity during lignan biosynthesis and are also involved in lignin, gossypol and pterocarpan biosynthesis. This gene family plays a vital role in enhancing stress resistance and in secondary cell-wall development, but systematical understanding is lacking in cotton. Results In this study, 107 GbDIRs and 107 GhDIRs were identified in Gossypium barbadense and Gossypium hirsutum, respectively. Most of these genes have a classical gene structure without intron and encode proteins containing a signal peptide. Phylogenetic analysis showed that cotton DIR genes were classified into four distinct subfamilies (a, b/d, e, and f). Of these groups, DIR-a and DIR-e were evolutionarily conserved, and segmental and tandem duplications contributed equally to their formation. In contrast, DIR-b/d mainly expanded by recent tandem duplications, accompanying with a number of gene clusters. With the rapid evolution, DIR-b/d-III was a Gossypium-specific clade involved in atropselective synthesis of gossypol. RNA-seq data highlighted GhDIRs in response to Verticillium dahliae infection and suggested that DIR gene family could confer Verticillium wilt resistance. We also identified candidate DIR genes related to fiber development in G. barbadense and G. hirsutum and revealed their differential expression. To further determine the involvement of DIR genes in fiber development, we overexpressed a fiber length-related gene GbDIR78 in Arabidopsis and validated its function in trichomes and hypocotyls. Conclusions These findings contribute novel insights towards the evolution of DIR gene family and provide valuable information for further understanding the roles of DIR genes in cotton fiber development as well as in stress responses.

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Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A13 of the S100 protein family

Biochemical Journal ◽

10.1042/bj3380583 ◽

1999 ◽

Vol 338 (3) ◽

pp. 583-589 ◽

Cited By ~ 36

Author(s):

Tsuyoshi SHISHIBORI ◽

Yuhta OYAMA ◽

Osamu MATSUSHITA ◽

Kayoko YAMASHITA ◽

Hiromi FURUICHI ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Calcium Binding ◽

Binding Proteins ◽

S100 Protein ◽

Reversed Phase ◽

Molecular Probes ◽

Calcium Binding Proteins ◽

Ige Mediated ◽

Human And Mouse

To investigate the roles of calcium-binding proteins in degranulation, we used three anti-allergic drugs, amlexanox, cromolyn and tranilast, which inhibit IgE-mediated degranulation of mast cells, as molecular probes in affinity chromatography. All of these drugs, which have different structures but similar function, scarcely bound to calmodulin in bovine lung extract, but bound to the same kinds of calcium-binding proteins, such as the 10-kDa proteins isolated in this study, calcyphosine and annexins I–V. The 10-kDa proteins obtained on three drug-coupled resins and on phenyl-Sepharose were analysed by reversed-phase HPLC. It was found that two characteristic 10-kDa proteins, one polar and one less polar, were bound with all three drugs, although S100A2 (S100L), of the S100 family, was bound with phenyl-Sepharose. The cDNA and deduced amino acid sequence proved our major polar protein to be identical with the calcium-binding protein in bovine amniotic fluid (CAAF1, S100A12). The cDNA and deduced amino acid sequence of the less-polar protein shared 95% homology with human and mouse S100A13. In addition, it was demonstrated that the native S100A12 and recombinant S100A12 and S100A13 bind to immobilized amlexanox. On the basis of these findings, we speculate that the three anti-allergic drugs might inhibit degranulation by binding with S100A12 and S100A13.

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