Search results for " mutation"
showing 10 items of 1212 documents
Pharmacophore-Based Design of New Chemical Scaffolds as Translational Readthrough-Inducing Drugs (TRIDs)
2020
[Image: see text] Translational readthrough-inducing drugs (TRIDs) rescue the functional full-length protein expression in genetic diseases, such as cystic fibrosis, caused by premature termination codons (PTCs). Small molecules have been developed as TRIDs to trick the ribosomal machinery during recognition of the PTC. Herein we report a computational study to identify new TRID scaffolds. A pharmacophore approach was carried out on compounds that showed readthrough activity. The pharmacophore model applied to screen different libraries containing more than 87000 compounds identified four hit-compounds presenting scaffolds with diversity from the oxadiazole lead. These compounds have been s…
Isolating, characterising and identifying a Cry1Ac resistance mutation in field populations of Helicoverpa punctigera
2018
AbstractTransgenic cotton expressing insecticidal proteins from Bacillus thuringiensis (Bt) has been grown in Australia for over 20 years and resistance remains the biggest threat. The native moth, Helicoverpa punctigera is a significant pest of cotton. A genotype causing resistance to Cry1Ac in H. punctigera was isolated from the field and a homozygous line established. The phenotype is recessive and homozygous individuals possess 113 fold resistance to Cry1Ac. Individuals that carry Cry1Ac resistance genes are rare in Australia with a frequency of 0.033 being detected in field populations. RNAseq, RT-PCR and DNA sequencing reveals a single nucleotide polymorphism at a splice site in the c…
Novel mutations in the voltage-gated sodium channel of pyrethroid-resistant Varroa destructor populations from the Southeastern USA
2016
The parasitic mite Varroa destructor has a significant worldwide impact on bee colony health. In the absence of control measures, parasitized colonies invariably collapse within 3 years. The synthetic pyrethroids tau-fluvalinate and flumethrin have proven very effective at managing this mite within apiaries, but intensive control programs based mainly on one active ingredient have led to many reports of pyrethroid resistance. In Europe, a modification of leucine to valine at position 925 (L925V) of the V. destructor voltage-gated sodium channel was correlated with resistance, the mutation being found at high frequency exclusively in hives with a recent history of pyrethroid treatment. Here,…
Mutations in the voltage-gated sodium channel gene associated with deltamethrin resistance in commercially sourced Phytoseiulus persimilis
2020
The implementation of Integrated Pest Management (IPM) in current agricultural practice is a convenient and very effective strategy to maintain pest populations under control. The use of Biological Control Agents, like Phytoseiulus persimilis, is key for the success of such approach. This predatory mite is widely used since it is very effective for controlling the two spotted spider mite (Tetranychus urticae), one of the most devastating pests worldwide. Here we show the identification of mutations located in the Voltage Gated Sodium Channel (VGSC) of P. persimilis, that correlate with the reduced susceptibility to deltamethrin observed in commercially sourced colonies of this predatory mit…
Polyamine Oxidase 5 loss-of-function mutations in Arabidopsis thaliana trigger metabolic and transcriptional reprogramming and promote salt stress to…
2017
The family of polyamine oxidases (PAO) in Arabidopsis (AtPAO1-5) mediates polyamine (PA) back-conversion, which reverses the PA biosynthetic pathway from spermine, and its structural isomer thermospermine (tSpm), into spermidine and then putrescine. Here, we have studied the involvement of PA back-conversion in Arabidopsis salinity tolerance. AtPAO5 is the Arabidopsis PAO gene member most transcriptionally induced by salt stress. Two independent loss-of-function mutants (atpao5-2 and atpao5-3) were found to exhibit constitutively higher tSpm levels, with associated increased salt tolerance. Using global transcriptional and metabolomic analyses, the underlying mechanisms were studied. Stimul…
Epigenetic and Genetic Contributions to Adaptation in Chlamydomonas
2017
Epigenetic modifications, such as DNA methylation or histone modifications, can be transmitted between cellular or organismal generations. However, there are no experiments measuring their role in adaptation, so here we use experimental evolution to investigate how epigenetic variation can contribute to adaptation. We manipulated DNA methylation and histone acetylation in the unicellular green alga Chlamydomonas reinhardtii both genetically and chemically to change the amount of epigenetic variation generated or transmitted in adapting populations in three different environments (salt stress, phosphate starvation, and high CO2) for two hundred asexual generations. We find that reducing the …
The roles of whole-genome and small-scale duplications in the functional specialization of Saccharomyces cerevisiae genes
2013
Researchers have long been enthralled with the idea that gene duplication can generate novel functions, crediting this process with great evolutionary importance. Empirical data shows that whole-genome duplications (WGDs) are more likely to be retained than small-scale duplications (SSDs), though their relative contribution to the functional fate of duplicates remains unexplored. Using the map of genetic interactions and the re-sequencing of 27 Saccharomyces cerevisiae genomes evolving for 2,200 generations we show that SSD-duplicates lead to neo-functionalization while WGD-duplicates partition ancestral functions. This conclusion is supported by: (a) SSD-duplicates establish more genetic i…
SHAPE MATTERS: EFFECT OF POINT MUTATIONS ON RNA SECONDARY STRUCTURE
2013
A suitable model to dive into the properties of genotype-phenotype landscapes is the relationship between RNA sequences and their corresponding minimum free energy secondary structures. Relevant issues related to molecular evolvability and robustness to mutations have been studied in this framework. Here, we analyze the one-mutant neighborhood of the predicted secondary structure of 46 different RNAs, including tRNAs, viroids, larger molecules such as Hepatitis-δ virus, and several random sequences. The probability distribution of the effect of point mutations in linear structural motifs of the secondary structure is well fit by Pareto or Lognormal probability distributions functions, indep…
Diversifying selection on MHC class I in the house sparrow (Passer domesticus).
2009
10 pages; International audience; Genes of the major histocompatibility complex (MHC) are the most polymorphic loci known in vertebrates. Two main hypotheses have been put forward to explain the maintenance of MHC diversity: pathogen-mediated selection and MHC-based mate choice. Host-parasite interactions can maintain MHC diversity via frequency-dependent selection, heterozygote advantage, and diversifying selection (spatially and/or temporally heterogeneous selection). In this study, we wished to investigate the nature of selection acting on the MHC class I across spatially structured populations of house sparrows (Passer domesticus) in France. To infer the nature of the selection, we comp…
Reverse-engineering the Arabidopsis thaliana transcriptional network under changing environmental conditions
2009
46 pages, 4 tables, 6 figures, 3 additinoal files.