polyphenism
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Environmental stressors can be key drivers of phenotypes, including reproductive strategies and morphological traits. The response to stress may be altered by the presence of microbial associates. For example, in aphids, facultative (secondary) bacterial symbionts can provide protection against natural enemies and stress induced by elevated temperatures. Furthermore, aphids exhibit phenotypic plasticity, producing winged (rather than wingless) progeny that may be better able to escape danger, and the combination of these factors improves the response to stress. How symbionts and phenotypic plasticity, both of which shape aphids' stress response, influence one another, and together influence host fitness, remains unclear. In this study, we investigate how environmental stressors drive shifts in fecundity and winged/wingless offspring production, and how secondary symbionts influence the process. We induced production of winged offspring through distinct environmental stressors, including exposure to aphid alarm pheromone and crowding, and, in one experiment, we assessed whether the aphid response is influenced by host plant. In the winged morph, energy needed for wing maintenance may lead to trade-offs with other traits, such as reproduction or symbiont maintenance. Potential trade-offs between symbiont maintenance and fitness have been proposed but have not been tested. Thus, beyond studying the production of offspring of alternative morphs, we also explore the influence of symbionts across wing/wingless polyphenism as well as symbiont interaction with cross-generational impacts of environmental stress on reproductive output. All environmental stressors resulted in increased production of winged offspring and shifts in fecundity rates. Additionally, in some cases, aphid host-by-symbiont interactions influenced fecundity. Stress on first-generation aphids had cross-generational impacts on second-generation adults, and the impact on fecundity was further influenced by the presence of secondary symbionts and presence/absence of wings. Our study suggests a complex interaction between beneficial symbionts and environmental stressors. Winged aphids have the advantage of being able to migrate out of danger with more ease, but energy needed for wing production and maintenance may come with reproductive costs for their mothers and for themselves, where in certain cases, these costs are altered by secondary symbionts.
- MeSH
- Bacteria MeSH
- hrách setý MeSH
- křídla zvířecí MeSH
- mšice * MeSH
- symbióza MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Juvenile hormone (JH) controls insect reproduction and development through an intracellular receptor complex comprising two bHLH-PAS proteins, the JH-binding Methoprene-tolerant (Met) and its partner Taiman (Tai). Many hemimetabolous insects including cockroaches strictly depend on JH for stimulation of vitellogenesis. In termites, the eusocial hemimetabolans, JH also regulates the development of caste polyphenism. Studies addressing the agonist ligand binding to recombinant JH receptors currently include three species belonging to two holometabolous insect orders, but none that would represent any of the hemimetabolous orders. Here, we examined JH receptors in two representatives of Blattodea, the cockroach Blattella germanica and the termite Prorhinotermes simplex. To test the JH-binding capacity of Met proteins from these species, we performed chemical synthesis and tritium labeling of the natural blattodean JH homolog, JH III. Our improved protocol increased the yield and specific activity of [10-3H]JH III relative to formerly available preparations. Met proteins from both species specifically bound [3H]JH III with high affinity, whereas Met variants mutated at a critical position within the ligand-binding domain were incapable of such binding. Furthermore, JH III and the synthetic JH mimic fenoxycarb stimulated dimerization between Met and Tai components of the respective JH receptors of both species. These data present primary evidence for agonist binding by JH receptors in any hemimetabolous species and provide a molecular basis for JH action in cockroaches and termites.
- MeSH
- Ectobiidae metabolismus MeSH
- hmyzí proteiny metabolismus MeSH
- Isoptera metabolismus MeSH
- seskviterpeny metabolismus MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Single nucleotide variants represent a prevalent form of genetic variation. Mutations in the coding regions are frequently associated with the development of various genetic diseases. Computational tools for the prediction of the effects of mutations on protein function are very important for analysis of single nucleotide variants and their prioritization for experimental characterization. Many computational tools are already widely employed for this purpose. Unfortunately, their comparison and further improvement is hindered by large overlaps between the training datasets and benchmark datasets, which lead to biased and overly optimistic reported performances. In this study, we have constructed three independent datasets by removing all duplicities, inconsistencies and mutations previously used in the training of evaluated tools. The benchmark dataset containing over 43,000 mutations was employed for the unbiased evaluation of eight established prediction tools: MAPP, nsSNPAnalyzer, PANTHER, PhD-SNP, PolyPhen-1, PolyPhen-2, SIFT and SNAP. The six best performing tools were combined into a consensus classifier PredictSNP, resulting into significantly improved prediction performance, and at the same time returned results for all mutations, confirming that consensus prediction represents an accurate and robust alternative to the predictions delivered by individual tools. A user-friendly web interface enables easy access to all eight prediction tools, the consensus classifier PredictSNP and annotations from the Protein Mutant Database and the UniProt database. The web server and the datasets are freely available to the academic community at http://loschmidt.chemi.muni.cz/predictsnp.
- MeSH
- algoritmy MeSH
- databáze proteinů MeSH
- fylogeneze MeSH
- genetická variace MeSH
- genetické nemoci vrozené genetika MeSH
- genom lidský MeSH
- internet MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé MeSH
- mutace * MeSH
- počítačová simulace MeSH
- software MeSH
- výpočetní biologie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hyperphenylalaninemia (HPA) is one of the most common metabolic disorders. HPA, which is transmitted by an autosomal recessive mode of inheritance, is caused by mutations of the phenylalanine hydroxylase gene. Most mutations are missense and lead to reduced protein stability and/or impaired catalytic function. The impact of such mutations varies, ranging from classical phenylketonuria (PKU), mild PKU, to non-PKU HPA phenotypes. Despite the fact that HPA is a monogenic disease, clinical data show that one PKU genotype can be associated with more in vivo phenotypes, which indicates the role of other (still unknown) factors. To better understand the phenotype-genotype relationships, we analyzed computationally the impact of missense mutations in homozygotes stored in the BIOPKU database. A total of 34 selected homozygous genotypes was divided into two main groups according to their phenotypes: (A) genotypes leading to non-PKU HPA or combined phenotype non-PKU HPA/mild PKU and (B) genotypes leading to classical PKU, mild PKU or combined phenotype mild PKU/classical PKU. Combining in silico analysis and molecular dynamics simulations (in total 3 μs) we described the structural impact of the mutations, which allowed us to separate 32 out of 34 mutations between groups A and B. Testing the simulation conditions revealed that the outcome of mutant simulations can be modulated by the ionic strength. We also employed programs SNPs3D, Polyphen-2, and SIFT but based on the predictions performed we were not able to discriminate mutations with mild and severe PKU phenotypes.
- MeSH
- fenotyp MeSH
- fenylalaninhydroxylasa chemie genetika MeSH
- fenylketonurie genetika patologie MeSH
- genotyp MeSH
- konformace proteinů MeSH
- lidé MeSH
- missense mutace genetika MeSH
- počítačová simulace MeSH
- simulace molekulární dynamiky MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Familial pancreatic cancer (FPC) is an established but rare inherited tumor syndrome that accounts for approximately 5% of pancreatic ductal adenocarcinoma (PDAC) cases. No major causative gene defect has yet been identified, but germline mutations in predisposition genes BRCA1/2, CDKN2A and PALB2 could be detected in 10-15% of analyzed families. Thus, the genetic basis of disease susceptibility in the majority of FPC families remains unknown. In an attempt to identify new candidate genes, we performed whole-genome sequencing on affected patients from 15 FPC families, without detecting BRCA1/2, CDKN2A or PALB2 mutations, using an Illumina based platform. Annotations from CADD, PolyPhen-2, SIFT, Mutation Taster and PROVEAN were used to assess the potential impact of a variant on the function of a gene. Variants that did not segregate with pancreatic disease in respective families were excluded. Potential predisposing candidate genes ATM, SUFU, DAB1, POLQ, FGFBP3, MAP3K3 and ACAD9 were identified in 7 of 15 families. All identified gene mutations segregated with pancreatic disease, but sometimes with incomplete penetrance. An analysis of up to 46 additional FPC families revealed that the identified gene mutations appeared to be unique in most cases, despite a potentially deleterious ACAD9 Ala326Thr germline variant, which occurred in 4 (8.7%) of 46 FPC families. Notably, affected PDAC patients within a family carried identical germline mutations in up to three different genes, e.g., DAB1, POLQ and FGFBP3. These results support the hypothesis that FPC is a highly heterogeneous polygenetic disease caused by low-frequency or rare variants.
- Publikační typ
- časopisecké články MeSH
Aphids display an extraordinary phenotypic plasticity ranging from widespread reproductive and wing polyphenisms to the occurrence of sterile or subfertile soldier morphs restricted to eusocial species of the subfamilies Eriosomatinae and Hormaphidinae. Individual morphs are specialized by their behavior, anatomy, and physiology to perform different roles in aphid societies at different stages of the life cycle. The capacity of the insects to cope with environmental stressors is under the control of a group of neuropeptides of the adipokinetic hormone/red pigment-concentrating hormone family (AKH/RPCH) that bind to a specific receptor (AKHR). Here, we describe the molecular characteristics of AKH and AKHR in the eusocial aphid Pseudoregma bambucicola. The sequence of the bioactive AKH decapeptide and the intron position in P. bambucicola AKH preprohormone were found to be identical to those in a phylogenetically distant aphid Dreyfusia spp. (Adelgidae). We detected four transcript variants of AKHR that are translated into three protein isoforms. Further, we analyzed AKH/AKHR expression in different tissues and insects of different castes. In wingless females, a remarkable amount of AKH mRNA was only expressed in the heads. In contrast, AKHR transcript levels increased in the order gut
- MeSH
- fylogeneze MeSH
- hmyzí hormony genetika metabolismus MeSH
- hmyzí proteiny MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- kyselina pyrrolidonkarboxylová analogy a deriváty metabolismus MeSH
- messenger RNA genetika MeSH
- molekulární sekvence - údaje MeSH
- mšice genetika růst a vývoj metabolismus MeSH
- oligopeptidy genetika metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- receptory glukagonu genetika metabolismus MeSH
- sekvence aminokyselin MeSH
- sekvence nukleotidů MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Objective: Previous studies have suggested an association between gout susceptibility and common dysfunctional variants in ATP-binding cassette transporter subfamily G member 2/breast cancer resistance protein (ABCG2/BCRP), including rs72552713 (Q126X) and rs2231142 (Q141K). However, the association of rare ABCG2 variants with gout is unknown. Therefore, we investigated the effects of rare ABCG2 variants on gout susceptibility in this study. Methods: We sequenced the exons of ABCG2 in 480 patients with gout and 480 healthy controls (Japanese males). We also performed functional analyses of non-synonymous variants of ABCG2 and analysed the correlation between urate transport function and scores from the protein prediction algorithms (Sorting Intolerant from Tolerant (SIFT) and Polymorphism Phenotyping v2 (PolyPhen-2)). Stratified association analyses and multivariate logistic regression analysis were performed to evaluate the effects of rare and common ABCG2 variants on gout susceptibility. Results: We identified 3 common and 19 rare non-synonymous variants of ABCG2. SIFT scores were significantly correlated with the urate transport function, although some ABCG2 variants showed inconsistent scores. When the effects of common variants were removed by stratified association analysis, the rare variants of ABCG2 were associated with a significantly increased risk of gout (OR=3.2, p=6.4×10-3). Multivariate logistic regression analysis revealed that the size effect of these rare ABCG2 variants (OR=2.7, p=3.0×10-3) was similar to that of the common variants, Q126X (OR=3.4, p=3.2×10-6) and Q141K (OR=2.3, p=2.7×10-16). Conclusions: This study revealed that multiple common and rare variants of ABCG2 are independently associated with gout. These results could support both the 'Common Disease, Common Variant' and 'Common Disease, Multiple Rare Variant' hypotheses for the association between ABCG2 and gout susceptibility.
- Publikační typ
- časopisecké články MeSH
