Reconstructing the complex evolutionary history of the fused Aco2 gene in fission yeast

The Aco2 gene of Schizosaccharomyces pombe was formed by gene fusion between curious partners, namely genes encoding the enzyme aconitase and a mitochondrial ribosomal protein. In addition to a full-length transcript, a truncated mRNA encoding only the N-terminal aconitase domain is produced by polyadenylation at an internal site. Protein products of the gene are found in the nucleus, mitochondria and cytoplasm, consistent with the presence of multiple subcellular targeting signals. To reconstruct the evolution of this complex gene, we studied homologous genes from a range of related species. We find evidence for a dynamic history within Taphrinomycotina, including: early evolution of a nuclear localization signal; creation of a 3’ intron that could be involved in regulating subcellular targeting; evolution of multiple peroxisomal targeting signals in different lineages; and recurrent gene loss. We present a likely stepwise model for the evolution of this remarkable gene and discuss alternative scenarios.

Download Full-text

Identification of Novel Plant Peroxisomal Targeting Signals by a Combination of Machine Learning Methods and in Vivo Subcellular Targeting Analyses

The Plant Cell ◽

10.1105/tpc.111.084095 ◽

2011 ◽

Vol 23 (4) ◽

pp. 1556-1572 ◽

Cited By ~ 74

Author(s):

Thomas Lingner ◽

Amr R. Kataya ◽

Gerardo E. Antonicelli ◽

Aline Benichou ◽

Kjersti Nilssen ◽

...

Keyword(s):

Machine Learning ◽

Subcellular Targeting ◽

Learning Methods ◽

Machine Learning Methods ◽

Peroxisomal Targeting ◽

Targeting Signals

Download Full-text

Characterization, prediction and evolution of plant peroxisomal targeting signals type 1 (PTS1s)

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ◽

10.1016/j.bbamcr.2016.01.001 ◽

2016 ◽

Vol 1863 (5) ◽

pp. 790-803 ◽

Cited By ~ 25

Author(s):

S. Reumann ◽

G. Chowdhary ◽

T. Lingner

Keyword(s):

Peroxisomal Targeting ◽

Targeting Signals

Download Full-text

Left-wing spectrum of the Czechoslovak political opposition in search of new solutions. The late 1980s to early 1990s

10.31168/2712-8342.2021.2.11 ◽

2021 ◽

pp. 154-178

Author(s):

Emil Vorachek ◽

Keyword(s):

Communist Party ◽

Future Development ◽

Left Wing ◽

Political Opposition ◽

Economic Changes ◽

Transformational Model ◽

History Of ◽

Alternative Scenarios ◽

The Revolution

The chapter is devoted to the history of the formation and activity of left-wing organizations in the Czechoslovak political opposition from the late 1980s to early 1990s. Those organizations were made up of diverse ideological currents from both inside and outside the ranks of the Communist Party of Czechoslovakia (СPCz). Attempts to develop alternative scenarios of social, political, and socio-economic changes in the country are examined. The left-wing had difficulties adaptating to the changing conditions provided by the leader of the revolution - the Civil Forum - towards the liberal transformational model. In general, during the period examined in the chapter, the forces of the left, for various reasons, failed to realize their vision for future development.

Download Full-text

ECG patterns related to arrhythmias and sudden death: channelopathies, early repolarization, and pre-excitation

ESC CardioMed ◽

10.1093/med/9780198784906.003.0074 ◽

2018 ◽

pp. 382-389

Author(s):

Wojciech Zareba ◽

Pyotr Platonov

Keyword(s):

Sudden Death ◽

Long Qt Syndrome ◽

Ventricular Arrhythmias ◽

Prior History ◽

Long Qt ◽

Early Repolarization ◽

Genes Encoding ◽

History Of ◽

Qt Syndrome ◽

Characteristic Features

Electrocardiogram (ECG) patterns recognized in patients with sudden death without structural abnormalities in the heart have guided cardiology over the last few decades towards a better understanding of the role of cardiac ion channels in physiology and in arrhythmogenicity in rare electrical diseases. The long QT syndrome became the paradigm for evaluating the association between specific ion channel abnormalities caused by mutations in genes encoding predominantly potassium and sodium channels and phenotypic ECG expression. Specific ECG patterns observed in long QT syndrome help in diagnosis and improve prognosis in patients affected by this disorder. Short QT syndrome also is characterized by specific patterns in repolarization morphology that relate to affected potassium current or calcium handling genes. Brugada syndrome and early repolarization syndrome are considered as J-wave syndromes, having some similarities in ECG features but with distinctive patterns associated with classical forms of these disorders. Spontaneous appearance of cove-type Brugada pattern is associated with a worse prognosis. Early repolarization patterns may also indicate prognosis in subjects with a prior history of cardiac arrest or ventricular arrhythmias or a family history of cardiac arrests. Catecholaminergic polymorphic ventricular tachycardia is another channelopathy without characteristic features in standard resting ECG but with characteristic polymorphic ventricular arrhythmias during catecholaminergic challenge (exercise test, stressing situations). Pre-excitation syndromes associated with sudden cardiac death are well recognized and current understanding of these disorders leads to a better therapy.

Download Full-text

Protective Effect of R Allele ofPON1Gene on the Coronary Artery Disease in the Presence of Specific Genetic Background

Disease Markers ◽

10.1155/2008/789291 ◽

2008 ◽

Vol 24 (2) ◽

pp. 81-88 ◽

Cited By ~ 10

Author(s):

Anna Balcerzyk ◽

Iwona Zak ◽

Jolanta Krauze

Keyword(s):

Protective Effect ◽

Blood Donors ◽

Study Groups ◽

Carrier State ◽

Pcr Rflp ◽

Environmental Background ◽

Genes Encoding ◽

History Of ◽

Polymorphic Variants ◽

Artery Disease

Background: Genetic susceptibility to CAD may be determined by polymorphic variants of genes encoding isoforms involved in the processes important in the pathogenesis of atherosclerosis, including lipids disorders. Participation of single polymorphic variants is relatively small, however its significance may increase in the presence of specific genetic or environmental background.Aim: The aim of the study was an evaluation a possible association between single polymorphic variants ofPON1, APOE, ABCA1andPPARAgenes and CAD and looking for specific multigene genotype patterns which differentiate study groups.Materials and methods: We studied 358 subjects:178 patients with angiographically confirmed CAD and 180 blood donors without history of CAD. Polymorphisms were genotyped using PCR-RFLP method.Results: We observed statistically significant differences in the frequencies of R allele and R allele carriers ofPON1gene between CAD and controls. The distribution of genotypes and alleles of other analyzed genes did not differentiate the study groups, however the presence of specific genotypes (APOE– ɛ3ɛ3, ɛ3ɛ2,ABCA1– AG,PPARA– GG) increased the protective effect of R allele.Conclusion: The present study revealed an independent protective association between carrier-state of PON1 R allele and CAD. This protective effect was especially strong in the presence of specific genotype arrangements of other analyzed genes.

Download Full-text

Functional Analyses of a Putative, Membrane-Bound, Peroxisomal Protein Import Mechanism from the Apicomplexan Protozoan Toxoplasma gondii

Genes ◽

10.3390/genes9090434 ◽

2018 ◽

Vol 9 (9) ◽

pp. 434

Author(s):

Alison Mbekeani ◽

Will Stanley ◽

Vishal Kalel ◽

Noa Dahan ◽

Einat Zalckvar ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Protein Import ◽

Fluorescent Protein ◽

Metabolic Energy ◽

Peroxisomal Protein ◽

Genes Encoding ◽

Peroxisomal Targeting ◽

Membrane Bound ◽

Green Fluorescent

Peroxisomes are central to eukaryotic metabolism, including the oxidation of fatty acids—which subsequently provide an important source of metabolic energy—and in the biosynthesis of cholesterol and plasmalogens. However, the presence and nature of peroxisomes in the parasitic apicomplexan protozoa remains controversial. A survey of the available genomes revealed that genes encoding peroxisome biogenesis factors, so-called peroxins (Pex), are only present in a subset of these parasites, the coccidia. The basic principle of peroxisomal protein import is evolutionarily conserved, proteins harbouring a peroxisomal-targeting signal 1 (PTS1) interact in the cytosol with the shuttling receptor Pex5 and are then imported into the peroxisome via the membrane-bound protein complex formed by Pex13 and Pex14. Surprisingly, whilst Pex5 is clearly identifiable, Pex13 and, perhaps, Pex14 are apparently absent from the coccidian genomes. To investigate the functionality of the PTS1 import mechanism in these parasites, expression of Pex5 from the model coccidian Toxoplasma gondii was shown to rescue the import defect of Pex5-deleted Saccharomyces cerevisiae. In support of these data, green fluorescent protein (GFP) bearing the enhanced (e)PTS1 known to efficiently localise to peroxisomes in yeast, localised to peroxisome-like bodies when expressed in Toxoplasma. Furthermore, the PTS1-binding domain of Pex5 and a PTS1 ligand from the putatively peroxisome-localised Toxoplasma sterol carrier protein (SCP2) were shown to interact in vitro. Taken together, these data demonstrate that the Pex5–PTS1 interaction is functional in the coccidia and indicate that a nonconventional peroxisomal import mechanism may operate in the absence of Pex13 and Pex14.

Download Full-text

Selecting among Alternative Scenarios of Human Evolution by Simulated Genetic Gradients

Genes ◽

10.3390/genes9100506 ◽

2018 ◽

Vol 9 (10) ◽

pp. 506 ◽

Cited By ~ 2

Author(s):

Catarina Branco ◽

Miguel Arenas

Keyword(s):

Human Evolution ◽

Simulated Data ◽

Real Data ◽

Population Admixture ◽

Evolutionary Processes ◽

Long Distance ◽

History Of ◽

Pros And Cons ◽

Alternative Scenarios ◽

And Migration

Selecting among alternative scenarios of human evolution is nowadays a common methodology to investigate the history of our species. This strategy is usually based on computer simulations of genetic data under different evolutionary scenarios, followed by a fitting of the simulated data with the real data. A recent trend in the investigation of ancestral evolutionary processes of modern humans is the application of genetic gradients as a measure of fitting, since evolutionary processes such as range expansions, range contractions, and population admixture (among others) can lead to different genetic gradients. In addition, this strategy allows the analysis of the genetic causes of the observed genetic gradients. Here, we review recent findings on the selection among alternative scenarios of human evolution based on simulated genetic gradients, including pros and cons. First, we describe common methodologies to simulate genetic gradients and apply them to select among alternative scenarios of human evolution. Next, we review previous studies on the influence of range expansions, population admixture, last glacial period, and migration with long-distance dispersal on genetic gradients for some regions of the world. Finally, we discuss this analytical approach, including technical limitations, required improvements, and advice. Although here we focus on human evolution, this approach could be extended to study other species.

Download Full-text

Cardiac Emerinopathy

Circulation Arrhythmia and Electrophysiology ◽

10.1161/circep.120.008712 ◽

2020 ◽

Vol 13 (10) ◽

Cited By ~ 1

Author(s):

Taisuke Ishikawa ◽

Hiroyuki Mishima ◽

Julien Barc ◽

Masanori P. Takahashi ◽

Keiichi Hirono ◽

...

Keyword(s):

Muscular Dystrophy ◽

Left Ventricular ◽

Cardiac Conduction ◽

Conduction Disturbance ◽

Ventricular Noncompaction ◽

Increased Risk ◽

Genes Encoding ◽

History Of ◽

Cardiac Conduction Defect ◽

Female Carriers

Background: Mutations in the nuclear envelope genes encoding LMNA and EMD are responsible for Emery-Dreifuss muscular dystrophy. However, LMNA mutations often manifest dilated cardiomyopathy with conduction disturbance without obvious skeletal myopathic complications. On the contrary, the phenotypic spectrums of EMD mutations are less clear. Our aims were to determine the prevalence of nonsyndromic forms of emerinopathy, which may underlie genetically undefined isolated cardiac conduction disturbance, and the etiology of thromboembolic complications associated with EMD mutations. Methods: Targeted exon sequencing was performed in 87 probands with familial sick sinus syndrome (n=36) and a progressive cardiac conduction defect (n=51). Results: We identified 3 X-linked recessive EMD mutations (start-loss, splicing, missense) in families with cardiac conduction disease. All 3 probands shared a common clinical phenotype of progressive atrial arrhythmias that ultimately resulted in atrial standstill associated with left ventricular noncompaction (LVNC), but they lacked early contractures and progressive muscle wasting and weakness characteristic of Emery-Dreifuss muscular dystrophy. Because the association of LVNC with EMD has never been reported, we further genetically screened 102 LVNC patients and found a frameshift EMD mutation in a boy with progressive atrial standstill and LVNC without complications of muscular dystrophy. All 6 male EMD mutation carriers of 4 families underwent pacemaker or defibrillator implantation, whereas 2 female carriers were asymptomatic. Notably, a strong family history of stroke observed in these families was probably due to the increased risk of thromboembolism attributable to both atrial standstill and LVNC. Conclusions: Cardiac emerinopathy is a novel nonsyndromic X-linked progressive atrial standstill associated with LVNC and increased risk of thromboembolism.

Download Full-text

A Novel FRET Approach Quantifies the Interaction Strength of Peroxisomal Targeting Signals and Their Receptor in Living Cells

Cells ◽

10.3390/cells9112381 ◽

2020 ◽

Vol 9 (11) ◽

pp. 2381

Author(s):

Bernhard Hochreiter ◽

Cheng-Shoong Chong ◽

Andreas Hartig ◽

Sebastian Maurer-Stroh ◽

Johannes Berger ◽

...

Keyword(s):

Mammalian Cells ◽

Interaction Strength ◽

Quantitative Measure ◽

Computational Prediction ◽

Technical Equipment ◽

Sequence Element ◽

Standard Equipment ◽

Peroxisomal Targeting ◽

Targeting Signals

Measuring Förster–resonance–energy–transfer (FRET) efficiency allows the investigation of protein–protein interactions (PPI), but extracting quantitative measures of affinity necessitates highly advanced technical equipment or isolated proteins. We demonstrate the validity of a recently suggested novel approach to quantitatively analyze FRET-based experiments in living mammalian cells using standard equipment using the interaction between different type-1 peroxisomal targeting signals (PTS1) and their soluble receptor peroxin 5 (PEX5) as a model system. Large data sets were obtained by flow cytometry coupled FRET measurements of cells expressing PTS1-tagged EGFP together with mCherry fused to the PTS1-binding domain of PEX5, and were subjected to a fitting algorithm extracting a quantitative measure of the interaction strength. This measure correlates with results obtained by in vitro techniques and a two-hybrid assay, but is unaffected by the distance between the fluorophores. Moreover, we introduce a live cell competition assay based on this approach, capable of depicting dose- and affinity-dependent modulation of the PPI. Using this system, we demonstrate the relevance of a sequence element next to the core tripeptide in PTS1 motifs for the interaction strength between PTS1 and PEX5, which is supported by a structure-based computational prediction of the binding energy indicating a direct involvement of this sequence in the interaction.

Download Full-text