scholarly journals Atypical Divergence of SARS-CoV-2 Orf8 from Orf7a within the Coronavirus Lineage Suggests Potential Stealthy Viral Strategies in Immune Evasion

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Russell Y. Neches ◽  
Nikos C. Kyrpides ◽  
Christos A. Ouzounis
Keyword(s):  
Sequence Space ◽  
High Accuracy ◽  
Striking Difference ◽  
Mammalian Host ◽  
Sequence Comparisons ◽  
Complex Interactions ◽  
Evolutionary Trajectories ◽  
Conservation Patterns ◽  
Paralog Gene ◽  
Sequence Similarities

ABSTRACT Orf8, one of the most puzzling genes in the SARS lineage of coronaviruses, marks a unique and striking difference in genome organization between SARS-CoV-2 and SARS-CoV-1. Here, using sequence comparisons, we unequivocally reveal the distant sequence similarities between SARS-CoV-2 Orf8 with its SARS-CoV-1 counterparts and the X4-like genes of coronaviruses, including its highly divergent “paralog” gene Orf7a, whose product is a potential immune antagonist of known structure. Supervised sequence space walks unravel identity levels that drop below 10% and yet exhibit subtle conservation patterns in this novel superfamily, characterized by an immunoglobulin-like beta sandwich topology. We document the high accuracy of the sequence space walk process in detail and characterize the subgroups of the superfamily in sequence space by systematic annotation of gene and taxon groups. While SARS-CoV-1 Orf7a and Orf8 genes are most similar to bat virus sequences, their SARS-CoV-2 counterparts are closer to pangolin virus homologs, reflecting the fine structure of conservation patterns within the SARS-CoV-2 genomes. The divergence between Orf7a and Orf8 is exceptionally idiosyncratic, since Orf7a is more constrained, whereas Orf8 is subject to rampant change, a peculiar feature that may be related to hitherto-unknown viral infection strategies. Despite their common origin, the Orf7a and Orf8 protein families exhibit different modes of evolutionary trajectories within the coronavirus lineage, which might be partly attributable to their complex interactions with the mammalian host cell, reflected by a multitude of functional associations of Orf8 in SARS-CoV-2 compared to a very small number of interactions discovered for Orf7a. IMPORTANCE Orf8 is one of the most puzzling genes in the SARS lineage of coronaviruses, including SARS-CoV-2. Using sophisticated sequence comparisons, we confirm its origins from Orf7a, another gene in the lineage that appears as more conserved, compared to Orf8. Orf7a is a potential immune antagonist of known structure, while a deletion of Orf8 was shown to decrease the severity of the infection in a cohort study. The subtle sequence similarities imply that Orf8 has the same immunoglobulin-like fold as Orf7a, confirmed by structure determination. We characterize the subgroups of this superfamily and demonstrate the highly idiosyncratic divergence patterns during the evolution of the virus.

scholarly journals Effects of intra-gene fitness interactions on the benefit of sexual recombination

2006 ◽  
Vol 34 (4) ◽  
pp. 560-561 ◽  
Author(s):  
R.A. Watson ◽  
D.M. Weinreich ◽  
J. Wakeley
Keyword(s):  
Nucleotide Sequence ◽  
Point Mutation ◽  
Sequence Space ◽  
Fitness Effect ◽  
Epistatic Interactions ◽  
Genetic Sequence ◽  
High Fitness ◽  
Sexual Recombination ◽  
Evolutionary Trajectories ◽  
Asexual Populations

Whereas spontaneous point mutation operates on nucleotides individually, sexual recombination manipulates the set of nucleotides within an allele as an essentially particulate unit. In principle, these two different scales of variation enable selection to follow fitness gradients in two different spaces: in nucleotide sequence space and allele sequence space respectively. Epistasis for fitness at these two scales, between nucleotides and between genes, may be qualitatively different and may significantly influence the advantage of mutation-based and recombination-based evolutionary trajectories respectively. We examine scenarios where the genetic sequence within a gene strongly influences the fitness effect of a mutation in that gene, whereas epistatic interactions between sites in different genes are weak or absent. We find that, in cases where beneficial alleles of a gene differ from one another at several nucleotide sites, sexual populations can exhibit enormous benefit compared with asexual populations: not only discovering fit genotypes faster than asexual populations, but also discovering high-fitness genotypes that are effectively not evolvable in asexual populations.

The development expression of the rat alpha-vascular and gamma-enteric smooth muscle isoactins: isolation and characterization of a rat gamma-enteric actin cDNA

1988 ◽  
Vol 8 (12) ◽  
pp. 5224-5231
Author(s):  
K M McHugh ◽  
J L Lessard
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Actin ◽  
The Other ◽  
Single Amino Acid ◽  
Cdna Clones ◽  
Muscle Actin ◽  
Adult Rats ◽  
Sequence Comparisons ◽  
Isolation And Characterization ◽  
Sequence Similarities

We have isolated and characterized two cDNA clones from whole rat stomach, pRV alpha A-19 and pRE gamma A-11, which are specific for the alpha-vascular and gamma-enteric smooth muscle isoactins, respectively. The rat gamma-enteric smooth muscle actin contains a single amino acid substitution of a proline for a glutamine at position 359 of the mature peptide when compared with the chicken gizzard gamma-actin sequence (J. Vandekerckhove and K. Weber, FEBS Lett. 102:219, 1979). Sequence comparisons of the 5' and 3' untranslated (UT) regions of the two smooth muscle actin cDNAs demonstrate that these regions contain no apparent sequence similarities. Additional comparisons of the 5' UT regions of the two smooth muscle actin cDNAs to all other known actin sequences reveal no apparent sequence similarities for the rat gamma-enteric isoactin within the 15 base pairs of sequence currently available, while the rat alpha-vascular isoactin contains two separate sequences which are similar to sequences within the 5' UT regions of the human and chicken alpha-vascular actin genes. A similar comparison of the 3' UT regions of the two smooth muscle actins demonstrates that the alpha-vascular isoactins do not contain the high degree of cross-species sequence conservation observed for the other isoactins and that the gamma-enteric isoactin contains an inverted sequence of 52 nucleotides which is similar to a sequence found within the 3' UT regions of the human, chicken, and rat beta-cytoplasmic isoactins. These observations complicate the apparent cross-species conservation of isotype specificity of these domains previously observed for the other actin isoforms. Northern blot analysis of day 15 rat embryos and newborn, day 19 postbirth, and adult rats demonstrates that the day 15 rat embryo displays low to undetectable levels of smooth muscle isoactin mRNA expression. By birth, the stomach and small intestine show dramatic increases in alpha-vascular and gamma-enteric actin expression. These initially high levels of expression decrease through day 19 to adulthood. In the adult rat, the uterus and aorta differ in their content of smooth muscle isoactin mRNA. These results demonstrate that the gamma-enteric and alpha-vascular isoactin mRNAs are coexpressed to various degrees in tissues which contain smooth muscle.

scholarly journals Differential Expression and Sequence Conservation of the Anaplasma marginale msp2 Gene Superfamily Outer Membrane Proteins

2006 ◽  
Vol 74 (6) ◽  
pp. 3471-3479 ◽  
Author(s):  
Susan M. Noh ◽  
Kelly A. Brayton ◽  
Donald P. Knowles ◽  
Joseph T. Agnes ◽  
Michael J. Dark ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Differential Expression ◽  
Outer Membrane Proteins ◽  
Anaplasma Marginale ◽  
Surface Proteins ◽  
Transcriptional Analysis ◽  
Mammalian Host ◽  
Anaplasma Ovis ◽  
Sequence Comparisons

ABSTRACT Bacterial pathogens in the genera Anaplasma and Ehrlichia encode a protein superfamily, pfam01617, which includes the predominant outer membrane proteins (OMPs) of each species, major surface protein 2 (MSP2) and MSP3 of Anaplasma marginale and Anaplasma ovis, Anaplasma phagocytophilum MSP2 (p44), Ehrlichia chaffeensis p28-OMP, Ehrlichia canis p30, and Ehrlichia ruminantium MAP1, and has been shown to be involved in both antigenic variation within the mammalian host and differential expression between the mammalian and arthropod hosts. Recently, complete sequencing of the A. marginale genome has identified an expanded set of genes, designated omp1-14, encoding new members of this superfamily. Transcriptional analysis indicated that, with the exception of the three smallest open reading frames, omp2, omp3, and omp6, these superfamily genes are transcribed in A. marginale-infected erythrocytes, tick midgut and salivary glands, and the IDE8 tick cell line. OMPs 1, 4, 7 to 9, and 11 were confirmed to be expressed as proteins by A. marginale within infected erythrocytes, with expression being either markedly lower (OMPs 1, 4, and 7 to 9) or absent (OMP11) in infected tick cells, which reflected regulation at the transcript level. Although the pfam01617 superfamily includes the antigenically variable MSP2 and MSP3 surface proteins, analysis of the omp1-14 sequences throughout a cycle of acute and persistent infection in the mammalian host and tick transmission reveals a high degree of conservation, an observation supported by sequence comparisons between the St. Maries strain and Florida strain genomes.

scholarly journals Phenylobacterium kunshanense sp. nov., isolated from the sludge of a pesticide manufacturing factory

2015 ◽  
Vol 65 (Pt_2) ◽  
pp. 325-330 ◽  
Author(s):  
Cuiwei Chu ◽  
Cansheng Yuan ◽  
Xin Liu ◽  
Li Yao ◽  
Jianchun Zhu ◽  
...  
Keyword(s):  
Type Species ◽  
Gene Sequence ◽  
Novel Species ◽  
Rrna Gene ◽  
Rrna Gene Sequence ◽  
Sequence Comparisons ◽  
Content Type ◽  
Link Type ◽  
Ubiquinone 10 ◽  
Sequence Similarities

A novel aerobic, Gram-stain-negative, motile bacterium, designated strain BUT-10T, was isolated from the sludge of a pesticide manufacturing factory in Kunshan, China. Cells were rod-shaped (0.4–0.45×0.9–1.4 µm) and colonies were white, circular with entire edges and had a smooth surface. The strain grew at 25–37 °C, at pH 6.0–8.0 and with 0–0.5 % NaCl. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that strain BUT-10T was a member of the genus Phenylobacterium , and showed highest sequence similarities to Phenylobacterium muchangponense A8T (97.49 %), Phenylobacterium immobile DSM 1986T (97.14 %) and Phenylobacterium lituiforme FaiI3T (96.34 %). Major fatty acids (>5 %) were summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c), C16 : 0 and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). The major isoprenoid quinone was ubiquinone-10. The DNA G+C content was 71.85 mol%. Strain BUT-10T showed low DNA–DNA relatedness with P. muchangponense A8T (15.7±2.9 %) and P. immobile DSM 1986T (12.8±1.1 %). On the basis of the phenotypic, phylogenetic and genotypic data, strain BUT-10T is considered to represent a novel species of the genus Phenylobacterium , for which the name Phenylobacterium kunshanense sp. nov. is proposed. The type strain is BUT-10T ( = CCTCC AB 2013085T = KCTC 42014T).

scholarly journals Predictive profiling of SARS-CoV-2 variants by deep mutational learning

2021 ◽  
Author(s):  
Joseph M Taft ◽  
Cedric R Weber ◽  
Beichen Gao ◽  
Roy A Ehling ◽  
Jiami Han ◽  
...  
Keyword(s):  
Machine Learning ◽  
Decision Making ◽  
Severe Acute Respiratory Syndrome ◽  
Sequence Space ◽  
Neutralizing Antibodies ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Primary Target ◽  
Engineering Technology ◽  
Evolutionary Trajectories

The continual evolution of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the emergence of variants that show resistance to vaccines and neutralizing antibodies threaten to prolong the coronavirus disease 2019 (COVID-19) pandemic. Selection and emergence of SARS-CoV-2 variants are driven in part by mutations within the viral spike protein and in particular the ACE2 receptor-binding domain (RBD), a primary target site for neutralizing antibodies. Here, we develop deep mutational learning (DML), a machine learning-guided protein engineering technology, which is used to interrogate a massive sequence space of combinatorial mutations, representing billions of RBD variants, by accurately predicting their impact on ACE2 binding and antibody escape. A highly diverse landscape of possible SARS-CoV-2 variants is identified that could emerge from a multitude of evolutionary trajectories. DML may be used for predictive profiling on current and prospective variants, including highly mutated variants such as omicron (B.1.1.529), thus supporting decision making for public heath as well as guiding the development of therapeutic antibody treatments and vaccines for COVID-19.

scholarly journals DISSEQT—DIStribution-based modeling of SEQuence space Time dynamics†

2019 ◽  
Vol 5 (2) ◽  
Author(s):  
R Henningsson ◽  
G Moratorio ◽  
A V Bordería ◽  
M Vignuzzi ◽  
M Fontes
Keyword(s):  
Sequence Space ◽  
Rna Virus ◽  
Population Based ◽  
Space Time ◽  
Fitness Landscapes ◽  
Microbial Populations ◽  
Dynamic Nature ◽  
Time Dynamics ◽  
Low Dimension ◽  
Evolutionary Trajectories

Abstract Rapidly evolving microbes are a challenge to model because of the volatile, complex, and dynamic nature of their populations. We developed the DISSEQT pipeline (DIStribution-based SEQuence space Time dynamics) for analyzing, visualizing, and predicting the evolution of heterogeneous biological populations in multidimensional genetic space, suited for population-based modeling of deep sequencing and high-throughput data. The pipeline is openly available on GitHub (https://github.com/rasmushenningsson/DISSEQT.jl, accessed 23 June 2019) and Synapse (https://www.synapse.org/#!Synapse: syn11425758, accessed 23 June 2019), covering the entire workflow from read alignment to visualization of results. Our pipeline is centered around robust dimension and model reduction algorithms for analysis of genotypic data with additional capabilities for including phenotypic features to explore dynamic genotype–phenotype maps. We illustrate its utility and capacity with examples from evolving RNA virus populations, which present one of the highest degrees of genetic heterogeneity within a given population found in nature. Using our pipeline, we empirically reconstruct the evolutionary trajectories of evolving populations in sequence space and genotype–phenotype fitness landscapes. We show that while sequence space is vastly multidimensional, the relevant genetic space of evolving microbial populations is of intrinsically low dimension. In addition, evolutionary trajectories of these populations can be faithfully monitored to identify the key minority genotypes contributing most to evolution. Finally, we show that empirical fitness landscapes, when reconstructed to include minority variants, can predict phenotype from genotype with high accuracy.

Zhihengliuella flava sp. nov., an actinobacterium isolated from sea sediment, and emended description of the genus Zhihengliuella

2013 ◽  
Vol 63 (Pt_12) ◽  
pp. 4760-4764 ◽  
Author(s):  
Moriyuki Hamada ◽  
Chiyo Shibata ◽  
Tomohiko Tamura ◽  
Ken-ichiro Suzuki
Keyword(s):  
Dna Hybridization ◽  
Rrna Gene ◽  
Phenotypic Characteristics ◽  
Sequence Comparisons ◽  
Content Type ◽  
Link Type ◽  
Gram Staining ◽  
Emended Description ◽  
Diamino Acid ◽  
Sequence Similarities

A novel Gram-staining-positive actinobacterium, designated H85-3T, was isolated from a sea sediment sample and its taxonomic position was investigated by a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that strain H85-3T was closely related to the members of the genus Zhihengliuella with pairwise sequence similarities of 97.4–98.6 %. The peptidoglycan of strain H85-3T was found to be of the A4α type with lysine as the diagnostic diamino acid. The menaquinones were MK-9, MK-10 and MK-8 (56 : 30 : 14) and the major cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0 and anteiso-C17 : 0. These data supported the affiliation of strain H85-3T to the genus Zhihengliuella . Meanwhile, the results of DNA–DNA hybridization, along with the differences in some phenotypic characteristics, indicated that strain H85-3T should be distinguished from the recognized species of the genus Zhihengliuella . Therefore, strain H85-3T represents a novel species of the genus Zhihengliuella , for which the name Zhihengliuella flava sp. nov. is proposed; the type strain is H85-3T ( = NBRC 109021T = DSM 26152T). An emended description of the genus Zhihengliuella is also proposed.

scholarly journals Preparation and Characterization of Neisseria meningitidis Mutants Deficient in Production of the Human Lactoferrin-Binding Proteins LbpA and LbpB

1998 ◽  
Vol 180 (12) ◽  
pp. 3080-3090 ◽  
Author(s):  
Robert A. Bonnah ◽  
Anthony B. Schryvers
Keyword(s):  
Neisseria Meningitidis ◽  
Binding Proteins ◽  
Binding Protein ◽  
Iron Acquisition ◽  
Outer Membrane Proteins ◽  
Mammalian Host ◽  
Human Pathogens ◽  
Sequence Comparisons ◽  
Isolation Technique

ABSTRACT Pathogenic members of the family Neisseriaceae produce specific receptors facilitating iron acquisition from transferrin (Tf) and lactoferrin (Lf) of their mammalian host. Tf receptors are composed of two outer membrane proteins, Tf-binding proteins A and B (TbpA and TbpB; formerly designated Tbp1 and Tbp2, respectively). Although only a single Lf-binding protein, LbpA (formerly designated Lbp1), had previously been recognized, we recently identified additional bacterial Lf-binding proteins in the human pathogens Neisseria meningitidis and Moraxella catarrhalis and the bovine pathogen Moraxella bovis by a modified affinity isolation technique (R. A. Bonnah, R.-H. Yu, and A. B. Schryvers, Microb. Pathog. 19:285–297, 1995). In this report, we characterize an open reading frame (ORF) located immediately upstream of theN. meningitidis B16B6 lbpA gene. Amino acid sequence comparisons of various TbpBs with the product of the translated DNA sequence from the upstream ORF suggests that the region encodes the Lf-binding protein B homolog (LbpB). The LbpB from strain B16B6 has two large stretches of negatively charged amino acids that are not present in the various transferrin receptor homologs (TbpBs). Expression of the recombinant LbpB protein as a fusion with maltose binding protein demonstrated functional Lf-binding activity. Studies with N. meningitidis isogenic mutants in which thelbpA gene and the ORF immediately upstream oflbpA (putative lbpB gene) were insertionally inactivated demonstrated that LbpA, but not LbpB, is essential for iron acquisition from Lf in vitro.

scholarly journals Phylogeny and Sequence Space: A Combined Approach to Analyze the Evolutionary Trajectories of Homologous Proteins. The Case Study of Aminodeoxychorismate Synthase

2019 ◽  
Vol 68 (1) ◽  
pp. 139-156
Author(s):  
Sylvain Lespinats ◽  
Olivier De Clerck ◽  
Benoît Colange ◽  
Vera Gorelova ◽  
Delphine Grando ◽  
...  
Keyword(s):  
Sequence Space ◽  
Combined Approach ◽  
Homologous Proteins ◽  
Evolutionary Trajectories

scholarly journals Phylogenetic Analyses of Phytopathogenic Isolates of Verticillium spp.

2006 ◽  
Vol 96 (6) ◽  
pp. 582-592 ◽  
Author(s):  
Qing-Ming Qin ◽  
Gary E. Vallad ◽  
Bo Ming Wu ◽  
Krishna V. Subbarao
Keyword(s):  
Genetic Relationships ◽  
Phylogenetic Analyses ◽  
Intergenic Spacer ◽  
Tubulin Gene ◽  
Sequence Comparisons ◽  
Distance Method ◽  
Pathogenicity Tests ◽  
Sequence Similarities ◽  
Β Tubulin ◽  
Potential Origin

To better understand the genetic relationships between Verticillium dahliae isolates from lettuce and other phytopathogenic Verticillium spp. isolates from various hosts and geographic locations, the complete intergenic spacer (IGS) region of the nuclear ribosomal RNA gene (rDNA) and the β-tubulin gene were amplified and sequenced. The sequences of the complete IGS region and the β-tubulin gene were used alone and in combination to infer genetic relationships among different isolates of Verticillium with the maximum-likelihood distance method. Phylogenetic analyses set sequences into four distinct groups comprising isolates of V. albo-atrum, V. tricorpus, and V. dahliae from cruciferous and noncruciferous hosts. Within the four Verticillium groups, isolates of V. dahliae from cruciferous hosts displayed the closest affinity to V. dahliae from noncruciferous hosts. Isolates of V. dahliae from noncruciferous hosts could be further divided into four subgroups based on sequence similarities within the IGS region. Cross-pathogenicity tests demonstrated that most Verticillium isolates were as virulent on other hosts as on their hosts of origin. A phenogram based on the cross pathogenicity of individual isolates resembled those derived from the IGS and β-tubulin sequence comparisons. On the basis of the data presented, the potential origin of some isolates of V. dahliae pathogenic on lettuce is proposed.

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