scholarly journals Positive Darwinian selection results in resistance to cardioactive toxins in true toads (Anura: Bufonidae)

2009 ◽  
Vol 5 (4) ◽  
pp. 513-516 ◽  
Author(s):  
David J. Moore ◽  
Damien C. T. Halliday ◽  
David M. Rowell ◽  
Anthony J. Robinson ◽  
J. Scott Keogh
Keyword(s):  
Positive Selection ◽  
Molecular Basis ◽  
Positive Darwinian Selection ◽  
Binding Region ◽  
Independent Evidence ◽  
The Family ◽  
Cardioactive Steroids ◽  
Distinct Sequence ◽  
Evolution Of Resistance ◽  
Homologous Amino Acid

Members of the Family Bufonidae, true toads, are famous for their endogenously synthesized cardioactive steroids that serve as defensive toxins. Evolution of resistance to these toxins is not understood. We sequenced a key region of the toxin's binding site in the Na + /K + ATPase for relevant taxa representing Hyloidea (including bufonids), Ranoidea and Archaeobatrachia and tested for positive selection in a phylogenetic context. Bufonidae were distinct from other Hyloidea at 4–6 of 12 sites and, with one exception, had a homologous amino acid sequence. Melanophryniscus stelzneri had a distinct sequence, consistent with other independent evidence for a differentiated toxin. Tests within Bufonidae detected positive selection within the binding region, providing, to our knowledge, the first evidence of this type for positive selection within Amphibia. There was no evidence for positive selection on Bufonidae or M. stelzneri lineages. Sequence change in Leptodactylus ocellatus , a leptodactylid predator of Bufonidae, provides a molecular basis for predator resistance possibly associated with gene duplication.

scholarly journals Exotoxins of Staphylococcus aureus

2000 ◽  
Vol 13 (1) ◽  
pp. 16-34 ◽  
Author(s):  
Martin M. Dinges ◽  
Paul M. Orwin ◽  
Patrick M. Schlievert
Keyword(s):  
Staphylococcus Aureus ◽  
Toxic Shock Syndrome ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Food Poisoning ◽  
Structure And Function ◽  
Toxic Shock ◽  
The Family ◽  
Toxic Shock Syndrome Toxin ◽  
And Function

SUMMARY This article reviews the literature regarding the structure and function of two types of exotoxins expressed by Staphylococcus aureus, pyrogenic toxin superantigens (PTSAgs) and hemolysins. The molecular basis of PTSAg toxicity is presented in the context of two diseases known to be caused by these exotoxins: toxic shock syndrome and staphylococcal food poisoning. The family of staphylococcal PTSAgs presently includes toxic shock syndrome toxin-1 (TSST-1) and most of the staphylococcal enterotoxins (SEs) (SEA, SEB, SEC, SED, SEE, SEG, and SEH). As the name implies, the PTSAgs are multifunctional proteins that invariably exhibit lethal activity, pyrogenicity, superantigenicity, and the capacity to induce lethal hypersensitivity to endotoxin. Other properties exhibited by one or more staphylococcal PTSAgs include emetic activity (SEs) and penetration across mucosal barriers (TSST-1). A detailed review of the molecular mechanisms underlying the toxicity of the staphylococcal hemolysins is also presented.

All in the Family: Primary Megakaryocytes for Studies of Platelet αIIbβ3 Signaling

2001 ◽  
Vol 86 (07) ◽  
pp. 259-265 ◽  
Author(s):  
Andrew Leavitt ◽  
Sanford Shattil
Keyword(s):  
Molecular Basis ◽  
Intrinsic Value ◽  
Model System ◽  
Integrin Signaling ◽  
Gene Products ◽  
Hematopoietic Stem ◽  
The Family ◽  
Viral Transduction ◽  
Inside Out ◽  
Platelet Formation

SummaryIntegrin αIIbβ3 mediates key platelet adhesive responses during hemostasis and thrombosis. Adhesive ligand binding to αIIbβ3 is regulated by “inside-out” signals, while adhesion-dependent cytoskeletal events are regulated by “outside-in” signals from αIIbβ3. Currently, the molecular basis of bidirectional αIIbβ3 signaling is incompletely understood. The functional assessment of integrin signaling pathways in nucleated cells has been facilitated by techniques such as viral transduction which enable expression of dominant-active and dominant-inhibitory gene products. This approach cannot be used with anucleate platelets. However, recent advances in the ability to expand human and murine megakaryocytes from hematopoietic stem cells provide a tractable and genetically manipulatable system for studies of αIIbβ3 signaling. This overview will discuss some of the advantages and limitations of this approach and provide examples of its utility. Thus, in addition to their intrinsic value for understanding hematopoiesis and platelet formation, primary megakaryocytes represent a model system complementary to platelets for unraveling the remaining mysteries of αIIbβ3 signaling.

Positive selection of three chitinase genes of the family 18 of glycoside hydrolases in mammals

Biologia ◽  
2009 ◽  
Vol 64 (4) ◽  
Author(s):  
Beibei He ◽  
Li Wang ◽  
Jinhong Wang ◽  
Gang Li ◽  
Shuyi Zhang
Keyword(s):  
Positive Selection ◽  
Catalytic Domain ◽  
Digestive Enzyme ◽  
Glycoside Hydrolases ◽  
Wide Range ◽  
The Family ◽  
Maximum Likelihood Methods ◽  
Mammalian Genomes ◽  
Acidic Mammalian Chitinase ◽  
Chitinase Genes

AbstractThe digestive enzyme chitinase degrades chitin, and is found in a wide range of organisms, from prokaryotes to eukaryotes. Although mammals cannot synthesize or assimilate chitin, several proteins of the glycoside hydrolase (GH) chitinase family GH18, including some with enzymatic activity, have recently been identified from mammalian genomes. Consequently, there is growing interest in molecular evolution of this family of proteins. Here we report on the use of maximum likelihood methods to test for evidence of positive selection in three genes of the chitinase family GH18, all of which are found in mammals. These focal genes are CHIA, CHIT1 and CHI3L1, which encode the chitinase proteins acidic mammalian chitinase, chitotriosidase and cartilage protein 39, respectively. The results of our analyses indicate that each of these genes has undergone independent selective pressure in their evolution. Additionally, we have found evidence of a signature of positive natural selection, with most sites identified as being subject to adaptive evolution located in the catalytic domain. Our results suggest that positive selection on these genes stems from their function in digestion and/or immunity.

scholarly journals Anticipation in an Indo-Canadian Family with Crohn's Disease

2001 ◽  
Vol 15 (10) ◽  
pp. 695-698 ◽  
Author(s):  
Hugh J Freeman ◽  
Noel B Hershfield
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Neurological Disorders ◽  
Molecular Basis ◽  
Present Report ◽  
Phenotypic Expression ◽  
Apparent Increase ◽  
The Family ◽  
Perianal Sepsis ◽  
Common Environmental Factor

Genetic anticipation, associated elsewhere with monogenic neurological disorders, has been hypothesized to be present in familial forms of Crohn's disease. Usually, with studies of parent-child pairs, the parent who is initially diagnosed is older at the onset of disease than the child. With each successive generation, an apparent increase in disease severity or behaviour occurs. This phenomenon is believed to have a molecular basis. In the present report, an Indo-Canadian family with Crohn's disease is described. In all members of the family, disease was diagnosed only after prolonged residence in Canada, supporting the view that Crohn's disease arises in individuals with a genetic predisposition following exposure to some, as yet unknown, common environmental factor. Three siblings with Crohn's disease, first diagnosed between ages 15 and 27 years, or six to 11 years after arrival in Canada, had phenotypically concordant disease localized in the ileum and colon, with fistulizing complications, including perianal sepsis. Crohn's disease was only diagnosed in the father at the age of 76 years, almost three decades after his arrival in Canada. His disease was localized to the ileum and had a fibrostenosing behaviour. This is the first reported instance of familial Crohn's disease in an immigrant population, illustrating potential biases in genetically based studies of Crohn's disease that rely solely on phenotypic expression.

scholarly journals The Parathyroid Hormone and Peptides Like It. Literature Review

2019 ◽  
Vol 74 (2) ◽  
pp. 136-144 ◽  
Author(s):  
Natalia G. Mokrysheva ◽  
Julia A. Krupinova ◽  
Elena V. Kovaleva
Keyword(s):  
Parathyroid Hormone ◽  
Phosphate Homeostasis ◽  
Amino Terminal ◽  
New Methods ◽  
Parathyroid Hormone Related Protein ◽  
Wide Range ◽  
The Family ◽  
Genes Encoding ◽  
Tuberoinfundibular Peptide ◽  
Homologous Amino Acid

Wide prevalence of the parathyroid glands pathology and the need for new methods of diagnosis and treatment are forcing researchers all over the world to go more deeply into the pathophysiological mechanisms. A parathyroid hormone (PTH) is main cause of mineral disorders. In addition, humans have a family with similar in structure molecules that contribute to the maintenance of calcium and phosphate homeostasis. The family includes PTH, parathyroid hormone-related protein (PTHrP) and tuberoinfundibular peptide 39 (TIP39, also known as PTH2). The genes encoding these peptides have highly homologous amino acid regions in the N-(amino) terminal receptor-binding sites of each family member, as well as the preserved structure of their organization, which seems to be due to the presence of one parent gene. The variety of classical and “non-classical” effects allows to expand the understanding of these substances and consider them as hormones that go beyond the regulation of phosphorus-calcium metabolism. The review provides information on the structure and biosynthesis of these peptides, as well as a wide range of their effects on the human body.

scholarly journals Molecular basis for the preferential recognition of β1,3‐1,4‐glucans by the family 11 carbohydrate‐binding module from Clostridium thermocellum

FEBS Journal ◽  
2019 ◽  
Vol 287 (13) ◽  
pp. 2723-2743 ◽  
Author(s):  
Diana O. Ribeiro ◽  
Aldino Viegas ◽  
Virgínia M. R. Pires ◽  
João Medeiros‐Silva ◽  
Pedro Bule ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Clostridium Thermocellum ◽  
Carbohydrate Binding ◽  
Carbohydrate Binding Module ◽  
The Family ◽  
Preferential Recognition

scholarly journals Genetic diversity, evolution and selection in the major histocompatibility complex DRB and DQB loci in the family Equidae

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Marie Klumplerova ◽  
Petra Splichalova ◽  
Jan Oppelt ◽  
Jan Futas ◽  
Aneta Kohutova ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Major Histocompatibility Complex ◽  
Positive Selection ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Depth Analysis ◽  
The Family ◽  
Antigen Presenting

Abstract Background The mammalian Major Histocompatibility Complex (MHC) is a genetic region containing highly polymorphic genes with immunological functions. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. The MHC class II sub-region contains genes expressed in antigen presenting cells. The antigen binding site is encoded by the second exon of genes encoding antigen presenting molecules. The exon 2 sequences of these MHC genes have evolved under the selective pressure of pathogens. Interspecific differences can be observed in the class II sub-region. The family Equidae includes a variety of domesticated, and free-ranging species inhabiting a range of habitats exposed to different pathogens and represents a model for studying this important part of the immunogenome. While equine MHC class II DRA and DQA loci have received attention, the genetic diversity and effects of selection on DRB and DQB loci have been largely overlooked. This study aimed to provide the first in-depth analysis of the MHC class II DRB and DQB loci in the Equidae family. Results Three DRB and two DQB genes were identified in the genomes of all equids. The genes DRB2, DRB3 and DQB3 showed high sequence conservation, while polymorphisms were more frequent at DRB1 and DQB1 across all species analyzed. DQB2 was not found in the genome of the Asiatic asses Equus hemionus kulan and E. h. onager. The bioinformatic analysis of non-zero-coverage-bases of DRB and DQB genes in 14 equine individual genomes revealed differences among individual genes. Evidence for recombination was found for DRB1, DRB2, DQB1 and DQB2 genes. Trans-species allele sharing was identified in all genes except DRB1. Site-specific selection analysis predicted genes evolving under positive selection both at DRB and DQB loci. No selected amino acid sites were identified in DQB3. Conclusions The organization of the MHC class II sub-region of equids is similar across all species of the family. Genomic sequences, along with phylogenetic trees suggesting effects of selection as well as trans-species polymorphism support the contention that pathogen-driven positive selection has shaped the MHC class II DRB/DQB sub-regions in the Equidae.

scholarly journals Recent host-shifts in ranaviruses: signatures of positive selection in the viral genome

2013 ◽  
Vol 94 (9) ◽  
pp. 2082-2093 ◽  
Author(s):  
A. Jeanine Abrams ◽  
David C. Cannatella ◽  
David M. Hillis ◽  
Sara L. Sawyer
Keyword(s):  
Positive Selection ◽  
Synonymous Substitution ◽  
Detection Methods ◽  
Host Switching ◽  
Synonymous Substitution Rate ◽  
Host Shifts ◽  
Selective Pressures ◽  
The Family ◽  
Viral Genes ◽  
Core Genes

Ranaviruses have been implicated in recent declines in global amphibian populations. Compared with the family Iridoviridae, to which the genus Ranavirus belongs, ranaviruses have a wide host range in that species/strains are known to infect fish, amphibians and reptiles, presumably due to recent host-switching events. We used eight sequenced ranavirus genomes and two selection-detection methods (site based and branch based) to identify genes that exhibited signatures of positive selection, potentially due to the selective pressures at play during host switching. We found evidence of positive selection acting on four genes via the site-based method, three of which were newly acquired genes unique to ranavirus genomes. Using the branch-based method, we identified eight additional candidate genes that exhibited signatures of dN /dS (non-synonymous/synonymous substitution rate) >1 in the clade where intense host switching had occurred. We found that these branch-specific patterns of elevated dN /dS were enriched in a small group of viral genes that have been acquired most recently in the ranavirus genome, compared with core genes that are shared among all members of the family Iridoviridae. Our results suggest that the group of newly acquired genes in the ranavirus genome may have undergone recent adaptive changes that have facilitated interspecies and interclass host switching.

scholarly journals Hitchhiking Under Positive Darwinian Selection

Genetics ◽  
2000 ◽  
Vol 155 (3) ◽  
pp. 1405-1413
Author(s):  
Justin C Fay ◽  
Chung-I Wu
Keyword(s):  
Positive Selection ◽  
Frequency Distribution ◽  
Stochastic Models ◽  
High Frequency ◽  
Intermediate Frequency ◽  
Positive Darwinian Selection ◽  
Evolutionary Processes ◽  
Darwinian Selection ◽  
High Frequencies ◽  
Unique Pattern

Abstract Positive selection can be inferred from its effect on linked neutral variation. In the restrictive case when there is no recombination, all linked variation is removed. If recombination is present but rare, both deterministic and stochastic models of positive selection show that linked variation hitchhikes to either low or high frequencies. While the frequency distribution of variation can be influenced by a number of evolutionary processes, an excess of derived variants at high frequency is a unique pattern produced by hitchhiking (derived refers to the nonancestral state as determined from an outgroup). We adopt a statistic, H, to measure an excess of high compared to intermediate frequency variants. Only a few high-frequency variants are needed to detect hitchhiking since not many are expected under neutrality. This is of particular utility in regions of low recombination where there is not much variation and in regions of normal or high recombination, where the hitchhiking effect can be limited to a small (<1 kb) region. Application of the H test to published surveys of Drosophila variation reveals an excess of high frequency variants that are likely to have been influenced by positive selection.

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