scholarly journals On the causes of evolutionary transition:transversion bias

2015 ◽  
Author(s):  
Arlin Stoltzfus ◽  
Ryan W. Norris
Keyword(s):  
Amino Acid ◽  
Statistical Power ◽  
Direct Evidence ◽  
Minor Role ◽  
Single Nucleotide ◽  
Fitness Effects ◽  
A Minor ◽  
Amino Acid Exchangeability ◽  
Growth Experiments ◽  
Null Expectation

A pattern in which nucleotide transitions are favored several-fold over transversions is common in molecular evolution. When this pattern occurs among amino acid replacements, explanations often invoke an effect of selection, on the grounds that transitions are more conservative in their effects on proteins. However, the underlying hypothesis of conservative transitions has never been tested directly. Here we assess support for this hypothesis using direct evidence: the fitness effects of mutations in actual proteins, measured via individual or paired growth experiments. We assembled data from 8 published studies, ranging in size from 24 to 757 single-nucleotide mutations that change an amino acid. Every study has the statistical power to reveal significant effects of amino acid exchangeability, and most studies have the power to discern a binary conservative-vs-radical distinction. However, only one study suggests that transitions are significantly more conservative than transversions. In the combined set of 1239 replacements, the chance that a transition is more conservative than a transversion is 53 % (95 % confidence interval, 50 % to 56 %), compared to the null expectation of 50 %. We show that this effect is not large compared to that of most biochemical factors, and is not large enough to explain the several-fold bias observed in evolution. In short, available data have the power to verify the "conservative transitions" hypothesis if true, but suggest instead that selection on proteins plays at best a minor role in the observed bias.

scholarly journals Spontaneous Mutations in thePlasmodium falciparumSarcoplasmic/ Endoplasmic Reticulum Ca2+-ATPase (PfATP6) Gene among Geographically Widespread Parasite Populations Unexposed to Artemisinin-Based Combination Therapies

2010 ◽  
Vol 55 (1) ◽  
pp. 94-100 ◽  
Author(s):  
Kazuyuki Tanabe ◽  
Sedigheh Zakeri ◽  
Nirianne Marie Q. Palacpac ◽  
Manada Afsharpad ◽  
Milijaona Randrianarivelojosia ◽  
...  
Keyword(s):  
Amino Acid ◽  
South America ◽  
Artemisinin Resistance ◽  
Common Snps ◽  
Nucleotide Polymorphisms ◽  
Combination Therapies ◽  
Single Nucleotide ◽  
Baseline Information ◽  
A Minor ◽  
Parasite Populations

ABSTRACTRecent reports on the decline of the efficacy of artemisinin-based combination therapies (ACTs) indicate a serious threat to malaria control. The endoplasmic/sarcoplasmic reticulum Ca2+-ATPase ortholog ofPlasmodium falciparum(PfSERCA) has been suggested to be the target of artemisinin and its derivatives. It is assumed that continuous artemisinin pressure will affect polymorphism of the PfSERCA gene (serca) if the protein is the target. Here, we investigated the polymorphism ofsercain parasite populations unexposed to ACTs to obtain baseline information for the study of potential artemisinin-driven selection of resistant parasites. Analysis of 656 full-length sequences from 13 parasite populations in Africa, Asia, Oceania, and South America revealed 64 single nucleotide polymorphisms (SNPs), of which 43 were newly identified and 38 resulted in amino acid substitutions. No isolates showed L263E and S769N substitutions, which were reportedly associated with artemisinin resistance. Among the four continents, the number of SNPs was highest in Africa. In Africa, Asia, and Oceania, common SNPs, or those with a minor allele frequency of ≥0.05, were less prevalent, with most SNPs noted to be continent specific, whereas in South America, common SNPs were highly prevalent and often shared with those in Africa. Of 50 amino acid haplotypes observed, only one haplotype (3D7 sequence) was seen in all four continents (64%). Forty-eight haplotypes had frequencies of less than 5%, and 40 haplotypes were continent specific. The geographical difference in the diversity and distribution ofsercaSNPs and haplotypes lays the groundwork for assessing whether some artemisinin resistance-associated mutations and haplotypes are selected by ACTs.

scholarly journals The fate of absorbed and exogenous ammonia as influenced by forage or forage–concentrate diets in growing sheep

1996 ◽  
Vol 76 (2) ◽  
pp. 231-248 ◽  
Author(s):  
G. E. Lobley ◽  
P. J. M. Weijs ◽  
A. Connell ◽  
A. G. Calder ◽  
D. S. Brown ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Ammonium Salt ◽  
Free Amino ◽  
Essential Amino Acids ◽  
Whole Body ◽  
Minor Role ◽  
N Removal ◽  
A Minor ◽  
Branched Chains

Changes in splanchnic energy and N metabolism were studied in sheep, prepared with vascular catheters across the portal-drained viscera (PDV) and the Liver, and maintained on supramaintenance intakes of either grass or grass + barley pellets. The animals were challenged, on both diets, with 4 d intra- mesenteric vein infusions of NH4CI (25 µmol/min) plus NH4HCO3(at either 0 or 125 µmol/min). On the final day of each treatment the natural abundance NH4Cl was replaced with15NH4Cl over a 10 h infusion while over the same period [l-13C]leucine was infused via a jugular vein. Measurements were made of blood flow plus mass transfers of NH3, urea, free amino acids and O2, across the PDV and liver. Enrichments of [14N15N]urea and [15N15N]urea plus [15N]glutamine, aspartate and glutamate were also monitored. Whole-body urea flux was determined by infusion of [14C]urea. At the end of the study the animals were infused for 3 h with15NH4CI, killed and liver samples assayed for intracellular free amino acid enrichments and concentrations. Blood flows across the splanchnic region were unaffected by either diet or level of ammonium salt infusion. At the lower ammonium salt infusion there was a trend for greater absorption of NH3across the PDV (P<0·10) with grass + barley than with the grass diet, while removal of urea was unaltered. At the higher ammonium salt infusions there was a significantly greater appearance of NH, across the PDV and this exceeded the extra infused. Urea-N removal, however, was also elevated and by more than that required to account for the additional NH3. The PDV contributed 19–28% to whole-body O2consumption and the liver 23–32%. Hepatic extraction of absorbed NH3was complete on all treatments and systemic pH remained constant. The fractions of urea-N apparently derived from NH3, were similar on the grass (0·59–0·64) and grass + barley (0·64–0·67) diets. Hepatic production of urea agreed well with urea flux measurements. Between the two levels of ammonium salt infusion and within diets the additional NH3removed across the PDV was accounted for by the increased urea-N production. The [14N15N]: [15N15N] ratio of the urea produced was 97:3, while the enrichment of hepatic intracellular free aspartate was lower than that of [14N15N]urea. Glutamine enrichments were 0·23–0·37 those of [14N15N]urea, indicating a minor role for those hepatocytes (probably perivenous) which contain glutamine synthetase (EC6.3.1.2). Leucine kinetics, either for the whole body or splanchnic tissues, were not different between diets or level of ammonium salt infusion, except for oxidation which was less on the grassfbarley ration. Amino acid concentrations were lower on the grass + barley diet but net PDV absorptions were similar. The pattern of essential amino acids absorbed into the PDV showed good agreement with the published composition of mixed rumen microbial protein. Fractional disappearances of absorbed free essential amino acids across the liver varied from 0·4 (branched chains) to near unity (histidine, phenylalanine)

scholarly journals Building a Barrier: The Influence of Different Wax Fractions on the Water Transpiration Barrier of Leaf Cuticles

2022 ◽  
Vol 12 ◽  
Author(s):  
Pascal Seufert ◽  
Simona Staiger ◽  
Katja Arand ◽  
Amauri Bueno ◽  
Markus Burghardt ◽  
...  
Keyword(s):  
Water Loss ◽  
Direct Evidence ◽  
Nerium Oleander ◽  
Minor Role ◽  
Terrestrial Plants ◽  
Hedera Helix ◽  
Cuticular Transpiration ◽  
Ilex Aquifolium ◽  
A Minor ◽  
Water Transpiration

Waxes are critical in limiting non-stomatal water loss in higher terrestrial plants by making up the limiting barrier for water diffusion across cuticles. Using a differential extraction protocol, we investigated the influence of various wax fractions on the cuticular transpiration barrier. Triterpenoids (TRPs) and very long-chain aliphatics (VLCAs) were selectively extracted from isolated adaxial leaf cuticles using methanol (MeOH) followed by chloroform (TCM). The water permeabilities of the native and the solvent-treated cuticles were measured gravimetrically. Seven plant species (Camellia sinensis, Ficus elastica, Hedera helix, Ilex aquifolium, Nerium oleander, Vinca minor, and Zamioculcas zamiifolia) with highly varying wax compositions ranging from nearly pure VLCA- to TRP-dominated waxes were selected. After TRP removal with MeOH, water permeability did not or only slightly increase. The subsequent VLCA extraction with TCM led to increases in cuticular water permeabilities by up to two orders of magnitude. These effects were consistent across all species investigated, providing direct evidence that the cuticular transpiration barrier is mainly composed of VLCA. In contrast, TRPs play no or only a minor role in controlling water loss.

scholarly journals Analysis of Somatostatin Receptors 2 and 5 Polymorphisms in Patients with Acromegaly

2005 ◽  
Vol 90 (8) ◽  
pp. 4824-4828 ◽  
Author(s):  
M. Filopanti ◽  
C. Ronchi ◽  
E. Ballarè ◽  
S. Bondioni ◽  
A. G. Lania ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Minor Role ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Igf I ◽  
A Minor ◽  
Serum Gh

Objective: The aim of the study was to investigate the possible correlation of single nucleotide polymorphisms in somatostatin receptor (SSTR)2 and SSTR5 genes with the responsiveness to somatostatin analogs in a cohort of acromegalic patients. Study Design: Three single nucleotide polymorphisms (a-83 g, c-57 g, and t80c) of SSTR2 and three (t-461c, c325t, and c1004t) of SSTR5 were analyzed in 66 acromegalic patients with different responsiveness to somatostatin analogs and 66 healthy controls. Results: Allele frequencies in patients and controls were similar. No association between SSTR2 genotypes and GH and IGF-I levels was found. When considering SSTR5 variants, patients homozygous or heterozygous for the substitution c1004 (P+) showed basal IGF-I levels significantly lower than patients homozygous for 1004t (P−). Moreover, serum GH levels were lower in patients with P+/T− haplotype (having c1004 allele and no t-461 allele) than in those with P−/T+. No correlation between SSTR2 and SSTR5 genotypes, responsiveness to somatostatin therapy, and mRNA expression in the removed adenomas (n = 10) was found. Conclusions: These data suggest a role for SSTR5 t–461c and c1004t alleles in influencing GH and IGF-I levels in patients with acromegaly, whereas SSTR2 and SSTR5 variants seem to have a minor role in determining the responsiveness to somatostatin analogs.

scholarly journals Pro219 is an electrostatic color determinant in the light-driven sodium pump KR2

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yuta Nakajima ◽  
Laura Pedraza-González ◽  
Leonardo Barneschi ◽  
Keiichi Inoue ◽  
Massimo Olivucci ◽  
...  
Keyword(s):  
Amino Acid ◽  
Electrostatic Interactions ◽  
Switching Function ◽  
Minor Role ◽  
Amino Acid Residues ◽  
Sodium Pumps ◽  
Environmental Consequences ◽  
Hydrogen Bond Networks ◽  
Microbial Rhodopsin ◽  
A Minor

AbstractColor tuning in animal and microbial rhodopsins has attracted the interest of many researchers, as the color of their common retinal chromophores is modulated by the amino acid residues forming the chromophore cavity. Critical cavity amino acid residues are often called “color switches”, as the rhodopsin color is effectively tuned through their substitution. Well-known color switches are the L/Q and A/TS switches located in the C and G helices of the microbial rhodopsin structure respectively. Recently, we reported on a third G/P switch located in the F helix of the light-driven sodium pumps of KR2 and JsNaR causing substantial spectral red-shifts in the latter with respect to the former. In order to investigate the molecular-level mechanism driving such switching function, here we present an exhaustive mutation, spectroscopic and computational investigation of the P219X mutant set of KR2. To do so, we study the changes in the absorption band of the 19 possible mutants and construct, semi-automatically, the corresponding hybrid quantum mechanics/molecular mechanics models. We found that the P219X feature a red-shifted light absorption with the only exception of P219R. The analysis of the corresponding models indicate that the G/P switch induces red-shifting variations via electrostatic interactions, while replacement-induced chromophore geometrical (steric) distortions play a minor role. However, the same analysis indicates that the P219R blue-shifted variant has a more complex origin involving both electrostatic and steric changes accompanied by protonation state and hydrogen bond networks modifications. These results make it difficult to extract simple rules or formulate theories for predicting how a switch operates without considering the atomistic details and environmental consequences of the side chain replacement.

scholarly journals Proteolysis of Bacteriophage λ CII byEscherichia coli FtsH (HflB)

2000 ◽  
Vol 182 (11) ◽  
pp. 3111-3116 ◽  
Author(s):  
Yoram Shotland ◽  
Amir Shifrin ◽  
Tamar Ziv ◽  
Dinah Teff ◽  
Simi Koby ◽  
...  
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Enzymatic Activity ◽  
Cleavage Site ◽  
Minor Role ◽  
Bacteriophage Λ ◽  
Small Peptides ◽  
A Minor ◽  
Insight Into ◽  
Byescherichia Coli

ABSTRACT FtsH (HflB) is a conserved, highly specific, ATP-dependent protease for which a number of substrates are known. The enzyme participates in the phage λ lysis-lysogeny decision by degrading the lambda CII transcriptional activator and by its response to inhibition by the λ CIII gene product. In order to gain further insight into the mechanism of the enzymatic activity of FtsH (HflB), we identified the peptides generated following proteolysis of the phage λ CII protein. It was found that FtsH (HflB) acts as an endopeptidase degrading CII into small peptides with limited amino acid specificity at the cleavage site. β-Casein, an unstructured substrate, is also degraded by FtsH (HflB), suggesting that protein structure may play a minor role in determining the products of proteolysis. The majority of the peptides produced were 13 to 20 residues long.

The Effect of Path Length and Display Size on Memory for Spatial Information

2012 ◽  
Vol 59 (3) ◽  
pp. 147-152 ◽  
Author(s):  
Katherine Guérard ◽  
Sébastien Tremblay
Keyword(s):  
Path Length ◽  
Potential Role ◽  
Spatial Information ◽  
Recall Performance ◽  
Minor Role ◽  
Length Effect ◽  
Serial Memory ◽  
Fixed Reference ◽  
A Minor

In serial memory for spatial information, some studies showed that recall performance suffers when the distance between successive locations increases relatively to the size of the display in which they are presented (the path length effect; e.g., Parmentier et al., 2005) but not when distance is increased by enlarging the size of the display (e.g., Smyth & Scholey, 1994). In the present study, we examined the effect of varying the absolute and relative distance between to-be-remembered items on memory for spatial information. We manipulated path length using small (15″) and large (64″) screens within the same design. In two experiments, we showed that distance was disruptive mainly when it is varied relatively to a fixed reference frame, though increasing the size of the display also had a small deleterious effect on recall. The insertion of a retention interval did not influence these effects, suggesting that rehearsal plays a minor role in mediating the effects of distance on serial spatial memory. We discuss the potential role of perceptual organization in light of the pattern of results.

Use of Different Tissue Thromboplastins in the Control of Anticoagulant-Therapy

1958 ◽  
Vol 02 (05/06) ◽  
pp. 462-480 ◽  
Author(s):  
Marc Verstraete ◽  
Patricia A. Clark ◽  
Irving S. Wright
Keyword(s):  
Prothrombin Time ◽  
Anticoagulant Therapy ◽  
Factor Vii ◽  
Rabbit Brain ◽  
Minor Role ◽  
Rabbit Lung ◽  
Coagulation Mechanism ◽  
Time Test ◽  
The One ◽  
A Minor

SummaryAn analysis of the results of prothrombin time tests with different types of thromboplastins sheds some light on the problem why the administration of coumarin is difficult to standardize in different centers. Our present ideas on the subject, based on experimental data may be summarized as follows.Several factors of the clotting mechanism are influenced by coumarin derivatives. The action of some of these factors is by-passed in the 1-stage prothrombin time test. The decrease of the prothrombin and factor VII levels may be evaluated in the 1-stage prothrombin time determination (Quick-test). The prolongation of the prothrombin times are, however, predominantly due to the decrease of factor VII activity, the prothrombin content remaining around 50 per cent of normal during an adequate anticoagulant therapy. It is unlikely that this degree of depression of prothrombin is of major significance in interfering with the coagulation mechanism in the protection against thromboembolism. It may, however, play a minor role, which has yet to be evaluated quantitatively. An exact evaluation of factor VII is, therefore, important for the guidance of anticoagulant therapy and the method of choice is the one which is most sensitive to changes in factor VII concentration. The 1-stage prothrombin time test with a rabbit lung thromboplastin seems the most suitable method because rabbit brain preparations exhibit a factor VII-like activity that is not present in rabbit lung preparations.

Produktivkraft als Versprechen

2016 ◽  
Vol 46 (185) ◽  
pp. 621-638 ◽  
Author(s):  
Christian Siefkes
Keyword(s):  
Private Consumption ◽  
Minor Role ◽  
Progressive Reduction ◽  
Internal Forces ◽  
A Minor

The ‘Fragment on Machines’ from Marx’s Grundrisse is often cited as an argument that the internal forces of capitalism will lead to its doom. But the argument that the progressive reduction of labor must doom capitalism lacks a proper foundation, as a comparison with the ‘Schemes of Reproduction’ given in Capital II shows. The latter, however, aren’t fully convincing either. In reality, more depends on the private consumption of capitalists than either model recognizes. Ultimately, most can be made of the ‘Fragment on Machines’ by reading it not as an exposure of capitalism’s internal contractions, but as a discussion of a possible communist future where labor (or work) will play but a minor role.

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