To keep ahead of the evolution of resistance to insecticides in mosquitoes, national malaria control programmes must make use of a range of insecticides, both old and new, while monitoring resistance mechanisms. The outdoor-biting malaria vector Anopheles arabiensis is of increasing concern for malaria transmission because it is apparently less susceptible to many indoor control interventions, yet knowledge of its mechanisms of resistance remains limited. Furthermore, comparatively little is known in general about resistance to non-pyrethroid insecticides such as pirimiphos-methyl (PM), which are crucial for effective control in the context of globally high resistance to pyrethroids. We performed a genome-wide association study to determine the molecular mechanisms of resistance to the pyrethroid deltamethrin (commonly used in bednets) and PM (widespread use for indoor spraying), in An. arabiensis from 2 regions in Tanzania. Genomic regions of positive selection in these populations were largely driven by copy number variants (CNVs) in gene families involved in metabolic resistance. We found evidence of a new gene cluster involved in resistance to PM, identifying a strong selective sweep tied to a CNV in the carboxylesterase genes Coeae2g - Coeae6g. Using complementary data from another malaria vector, An. coluzzii, in Ghana, we show that copy number at this locus is significantly associated with PM resistance. Similarly, for deltamethrin, resistance was strongly associated with a novel CNV allele in the Cyp6aa / Cyp6p cluster (Cyp6aap_Dup33). Against this background of metabolic resistance, resistance caused by mutations in the insecticide target sites was very rare or absent. Mutations in the pyrethroid target site Vgsc were at very low frequency in Tanzania, yet combining these samples with 3 An. arabiensis individuals from West Africa revealed a startling evolutionary diversity, with up to 5 independent origins of Vgsc-995 mutations found within just 8 haplotypes. Thus, despite having been first recorded over 10 years ago, Vgsc resistance mutations in Tanzanian An. arabiensis have remained at stable low frequencies. Overall, our results provide a new copy number marker for monitoring resistance to PM in malaria mosquitoes, and reveal the complex picture of resistance patterns in An. arabiensis.

• MeSH
• Anopheles * genetika   účinky léků   MeSH
• celogenomová asociační studie MeSH
• insekticidy * farmakologie   MeSH
• komáří přenašeči * genetika   účinky léků   MeSH
• malárie prevence a kontrola   přenos   MeSH
• nitrily * farmakologie   MeSH
• organothiofosforové sloučeniny farmakologie   MeSH
• pyrethriny * farmakologie   MeSH
• rezistence k insekticidům * genetika   MeSH
• selekce (genetika) MeSH
• variabilita počtu kopií segmentů DNA * genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Tanzanie MeSH
• Názvy látek
• decamethrin MeSH Prohlížeč
• insekticidy * MeSH
• nitrily * MeSH
• organothiofosforové sloučeniny MeSH
• pirimiphos methyl MeSH Prohlížeč
• pyrethriny * MeSH

To keep ahead of the evolution of resistance to insecticides in mosquitoes, national malaria control programmes must make use of a range of insecticides, both old and new, while monitoring resistance mechanisms. Knowledge of the mechanisms of resistance remains limited in Anopheles arabiensis, which in many parts of Africa is of increasing importance because it is apparently less susceptible to many indoor control interventions. Furthermore, comparatively little is known in general about resistance to non-pyrethroid insecticides such as pirimiphos-methyl (PM), which are crucial for effective control in the context of resistance to pyrethroids. We performed a genome-wide association study to determine the molecular mechanisms of resistance to deltamethrin (commonly used in bednets) and PM, in An. arabiensis from two regions in Tanzania. Genomic regions of positive selection in these populations were largely driven by copy number variants (CNVs) in gene families involved in resistance to these two insecticides. We found evidence of a new gene cluster involved in resistance to PM, identifying a strong selective sweep tied to a CNV in the Coeae2g-Coeae6g cluster of carboxylesterase genes. Using complementary data from An. coluzzii in Ghana, we show that copy number at this locus is significantly associated with PM resistance. Similarly, for deltamethrin, resistance was strongly associated with a novel CNV allele in the Cyp6aa / Cyp6p cluster. Against this background of metabolic resistance, target site resistance was very rare or absent for both insecticides. Mutations in the pyrethroid target site Vgsc were at very low frequency in Tanzania, yet combining these samples with three An. arabiensis individuals from West Africa revealed a startling diversity of evolutionary origins of target site resistance, with up to 5 independent origins of Vgsc-995 mutations found within just 8 haplotypes. Thus, despite having been first recorded over 10 years ago, Vgsc resistance mutations in Tanzanian An. arabiensis have remained at stable low frequencies. Overall, our results provide a new copy number marker for monitoring resistance to PM in malaria mosquitoes, and reveal the complex picture of resistance patterns in An. arabiensis.

• Klíčová slova
• Anopheles, Carboxylesterase, GWAS, genomic surveillance, insecticide resistance,
• Publikační typ
• časopisecké články MeSH
• preprinty MeSH

The alfalfa weevil Hypera postica, native to the Western Palearctic, is an invasive legume pest with two divergent mitochondrial clades in its invading regions, the Western clade and the Eastern/Egyptian clade. However, knowledge regarding the native populations is limited. The Western clade is infected with the endosymbiotic bacteria Wolbachia that cause cytoplasmic incompatibility in host weevils. Our aim was to elucidate the spatial genetic structure of this insect and the effect of Wolbachia on its population diversity. We analyzed two mitochondrial and two nuclear genes of the weevil from its native ranges. The Western clade was distributed in western/central Europe, whereas the Eastern/Egyptian clade was distributed from the Mediterranean basin to central Asia. Intermediate mitotypes were found from the Balkans to central Asia. Most Western clade individuals in western Europe were infected with an identical Wolbachia strain. Mitochondrial genetic diversity of the infected individuals was minimal. The infected clades demonstrated a higher nonsynonymous/synonymous substitution rate ratio than the uninfected clades, suggesting a higher fixation of nonsynonymous mutations due to a selective sweep by Wolbachia. Trans-Mediterranean and within-European dispersal routes were supported. We suggest that the ancestral populations diversified by geographic isolation due to glaciations and that the diversity was reduced in the west by a recent Wolbachia-driven sweep(s). The intermediate clade exhibited a body size and host plant that differed from the other clades. Pros and cons of the possible use of infected-clade males to control uninfected populations are discussed.

• MeSH
• fylogeneze MeSH
• fylogeografie MeSH
• genetická variace genetika   MeSH
• haplotypy genetika   MeSH
• mitochondrie genetika   MeSH
• nosatcovití genetika   mikrobiologie   MeSH
• velikost těla MeSH
• Wolbachia * MeSH
• zavlečené druhy MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Asie MeSH
• Evropa MeSH

A capillary electrophoretic (CE) method using a short-sweep approach and laser-induced fluorescence (LIF) detection (ShortSweepCE-LIF) was developed for determination of Zn2+ and Cd2+ as complexes with highly selective and sensitive fluorescent probe FluoZin-3. The ShortSweepCE-LIF method, established in this work, can be used for examining competitive Zn2+ and Cd2+ binding properties of metalloproteins or peptides. The parameters including background electrolyte composition, injection pressure and time as well as separation voltage were investigated. Under the optimized conditions, 80 mM HEPES, pH 7.4, with 1.5 μM FluoZin-3 was used as an electrolyte, hydrodynamic injection was performed at 50 mbar for 5 s, and separation voltage of 25 kV. Limits of detection for Zn2+ and Cd2+ were 4 and 125 nM, respectively. The developed method was demonstrated in a study of interactions between metalothionein-2a isoform and metal ions Zn2+, Co2+ and Cd2+. It was found that FluoZin-3 was able to extract a single Zn2+ ion, while added Co2+ (in surplus) extracted only 2.4 Zn2+ ions, and Cd2+ extracted all 7 Zn2+ ions present in the metalothionein molecule.

• Klíčová slova
• Cadmium, Capillary electrophoresis, FluoZin-3, Metal ions, Metalothionein, Zinc,
• MeSH
• elektroforéza kapilární MeSH
• fluorescenční barviva chemie   MeSH
• ionty analýza   MeSH
• kadmium analýza   MeSH
• metalothionein analýza   MeSH
• optické zobrazování * MeSH
• polycyklické sloučeniny chemie   MeSH
• zinek analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fluorescenční barviva MeSH
• FluoZin-3 MeSH Prohlížeč
• ionty MeSH
• kadmium MeSH
• metalothionein MeSH
• polycyklické sloučeniny MeSH
• zinek MeSH

Crop domestication is a co-evolutionary process that has rendered plants and animals significantly dependent on human interventions for survival and propagation. Grain legumes have played an important role in the development of Neolithic agriculture some 12,000 years ago. Despite being early companions of cereals in the origin and evolution of agriculture, the understanding of grain legume domestication has lagged behind that of cereals. Adapting plants for human use has resulted in distinct morpho-physiological changes between the wild ancestors and domesticates, and this distinction has been the focus of several studies aimed at understanding the domestication process and the genetic diversity bottlenecks created. Growing evidence from research on archeological remains, combined with genetic analysis and the geographical distribution of wild forms, has improved the resolution of the process of domestication, diversification and crop improvement. In this review, we summarize the significance of legume wild relatives as reservoirs of novel genetic variation for crop breeding programs. We describe key legume features, which evolved in response to anthropogenic activities. Here, we highlight how whole genome sequencing and incorporation of omics-level data have expanded our capacity to monitor the genetic changes accompanying these processes. Finally, we present our perspective on alternative routes centered on de novo domestication and re-domestication to impart significant agronomic advances of novel crops over existing commodities. A finely resolved domestication history of grain legumes will uncover future breeding targets to develop modern cultivars enriched with alleles that improve yield, quality and stress tolerance.

• Klíčová slova
• Crop wild relatives, Diversification, Domestication, Genes, Grain legumes, Selective sweeps,
• MeSH
• domestikace * MeSH
• Fabaceae * genetika   MeSH
• jedlá semena genetika   MeSH
• lidé MeSH
• šlechtění rostlin MeSH
• zemědělské plodiny genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Despite advances in sequencing, the goal of obtaining a comprehensive view of genetic variation in populations is still far from reached. We sequenced 180 lines of A. thaliana from Sweden to obtain as complete a picture as possible of variation in a single region. Whereas simple polymorphisms in the unique portion of the genome are readily identified, other polymorphisms are not. The massive variation in genome size identified by flow cytometry seems largely to be due to 45S rDNA copy number variation, with lines from northern Sweden having particularly large numbers of copies. Strong selection is evident in the form of long-range linkage disequilibrium (LD), as well as in LD between nearby compensatory mutations. Many footprints of selective sweeps were found in lines from northern Sweden, and a massive global sweep was shown to have involved a 700-kb transposition.

• MeSH
• Arabidopsis genetika   MeSH
• celogenomová asociační studie MeSH
• chromozomy rostlin MeSH
• genetická variace * MeSH
• genom rostlinný * MeSH
• jednonukleotidový polymorfismus MeSH
• mapování chromozomů MeSH
• molekulární evoluce MeSH
• mutace INDEL MeSH
• populační genetika MeSH
• selekce (genetika) * MeSH
• variabilita počtu kopií segmentů DNA MeSH
• vazebná nerovnováha MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Švédsko MeSH

The recently introduced orientation selective deep brain stimulation (OS-DBS) technique freely controls the direction of the electric field's spatial gradient by using multiple contacts with independent current sources within a multielectrode array. The goal of OS-DBS is to align the electrical field along the axonal track of interest passing through the stimulation site. Here we utilized OS-DBS with a planar 3-channel electrode for stimulating the rat entorhinal cortex (EC) and medial septal nucleus (MSN), two promising areas for DBS treatment of Alzheimer's disease. The brain responses to OS-DBS were monitored by whole brain functional magnetic resonance imaging (fMRI) at 9.4 T with Multi-Band Sweep Imaging with Fourier Transformation (MB-SWIFT). Varying the in-plane OS-DBS stimulation angle in the EC resulted in activity modulation of multiple downstream brain areas involved in memory and cognition. Contrary to that, no angle dependence of brain activations was observed when stimulating the MSN, consistent with predictions based on the electrode configuration and on the main axonal directions of the targets derived from diffusion MRI tractography and histology. We conclude that tuning the OS-DBS stimulation angle modulates the activation of brain areas relevant to Alzheimer's disease, thus holding great promise in the DBS treatment of the disease.

• MeSH
• Alzheimerova nemoc * diagnostické zobrazování   terapie   MeSH
• cortex entorhinalis diagnostické zobrazování   fyziologie   MeSH
• hluboká mozková stimulace * metody   MeSH
• kognice MeSH
• krysa rodu Rattus MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozek MeSH
• septální jádra * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Speciation is a continuous process during which genetic changes gradually accumulate in the genomes of diverging species. Recent studies have documented highly heterogeneous differentiation landscapes, with distinct regions of elevated differentiation ("differentiation islands") widespread across genomes. However, it remains unclear which processes drive the evolution of differentiation islands; how the differentiation landscape evolves as speciation advances; and ultimately, how differentiation islands are related to speciation. Here, we addressed these questions based on population genetic analyses of 200 resequenced genomes from 10 populations of four Ficedula flycatcher sister species. We show that a heterogeneous differentiation landscape starts emerging among populations within species, and differentiation islands evolve recurrently in the very same genomic regions among independent lineages. Contrary to expectations from models that interpret differentiation islands as genomic regions involved in reproductive isolation that are shielded from gene flow, patterns of sequence divergence (d(xy) and relative node depth) do not support a major role of gene flow in the evolution of the differentiation landscape in these species. Instead, as predicted by models of linked selection, genome-wide variation in diversity and differentiation can be explained by variation in recombination rate and the density of targets for selection. We thus conclude that the heterogeneous landscape of differentiation in Ficedula flycatchers evolves mainly as the result of background selection and selective sweeps in genomic regions of low recombination. Our results emphasize the necessity of incorporating linked selection as a null model to identify genome regions involved in adaptation and speciation.

• MeSH
• druhová specificita MeSH
• genom MeSH
• genomika MeSH
• genotypizační techniky MeSH
• jednonukleotidový polymorfismus MeSH
• Passeriformes klasifikace   genetika   MeSH
• populační genetika MeSH
• rekombinace genetická * MeSH
• reprodukční izolace MeSH
• sekvenční analýza DNA MeSH
• selekce (genetika) * MeSH
• tok genů MeSH
• vznik druhů (genetika) * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: The somatosensory evoked potentials of the median nerve (SEP) were registered intracerebrally in 12 subjects to elucidate the origin of N30 component and its behavior in the motor 'gating' tasks. METHODS: The recordings were done from the electrodes which were inserted within the cortex of frontal lobe in the pre-surgical phase of epilepsy surgery. The registrations focused on the precentral N30 SEP component and its behaviour under the 'gating' paradigms. Two different 'gating' paradigms, motor and mental, were used and the SEP then were recorded in 3 conditions: (1) normal (N) paradigm, during which the subjects were instructed not to perform any movement by the stimulated hand, or to mentally simulate the movement; (2) active movement (AM) paradigm, during which the subjects were instructed to perform the active movement as the internal motor sequence test by the fingers of the hand of the stimulated limb; (3) mental movement simulation (MMS), during which the subjects were instructed to only mentally simulate the movements performed in the previous paradigm, and this 'virtual' movement also involved the hand of the stimulated limb. The recordings were done at least twice in each paradigm and averaged runs of 2000 artefact-free sweeps were used for the analysis. RESULTS: The results demonstrated that the precentral N30 component of SEP is generated only in the pre-motor area, either dorsolaterally or mesially, which consists of Brodmann's areas 6 and 8, and their borders. Only the N30 potentials recorded there in 7 subjects had a shape and character of 'near-field' potential. The behaviour of the N30 component when recorded in the AM and MMS paradigms was different depending on the fact of whether they were recorded dorsolaterally or mesially. When there was a clear 'near-field' N30 potential recorded mesially, there was a certain gating present during the AM paradigm, i.e. during the performance of movement. However, the gating caused by the mental movement simulation in the MMS paradigm was substantially more expressed, and the N30 wave practically disappeared in some cases. On the contrary, the gating of the N30 wave, recorded in the frontal dorsolateral premotor cortex (DLPC), was almost complete when the AM (active movement) paradigm was employed, and it was only partial when the MMS paradigm (mental movement simulation) was employed. CONCLUSIONS: The results of N30 registrations in our group of patients strongly support the theory of separate generator (or generators) of the N30 wave within the premotor cortex. They also brought forward evidence that the dorsolateral premotor cortex (Brodmann's areas 6 and 8) serves as the substrate of the 'motor execution' process, and the mesial frontal cortex (Brodmann's area 6) serves as the substrate of the 'motor planning' process. Further research should focus on the mutual registration of neurophysiological phenomena and imaging phenomena to obtain new data, which will be able to more precisely elucidate the workings of the premotor cortex during the whole process of motor performance.

• MeSH
• dospělí MeSH
• elektrody MeSH
• elektroencefalografie MeSH
• epilepsie parciální patofyziologie   MeSH
• funkční lateralita MeSH
• lidé MeSH
• mapování mozku MeSH
• nervus medianus patofyziologie   MeSH
• pohyb fyziologie   MeSH
• postura těla MeSH
• prefrontální mozková kůra anatomie a histologie   patofyziologie   MeSH
• psychomotorický výkon MeSH
• ruka MeSH
• somatosenzorické evokované potenciály fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

A major aim of evolutionary biology is to understand why patterns of genomic diversity vary within taxa and space. Large-scale genomic studies of widespread species are useful for studying how environment and demography shape patterns of genomic divergence. Here, we describe one of the most geographically comprehensive surveys of genomic variation in a wild vertebrate to date; the great tit (Parus major) HapMap project. We screened ca 500,000 SNP markers across 647 individuals from 29 populations, spanning ~30 degrees of latitude and 40 degrees of longitude - almost the entire geographical range of the European subspecies. Genome-wide variation was consistent with a recent colonisation across Europe from a South-East European refugium, with bottlenecks and reduced genetic diversity in island populations. Differentiation across the genome was highly heterogeneous, with clear 'islands of differentiation', even among populations with very low levels of genome-wide differentiation. Low local recombination rates were a strong predictor of high local genomic differentiation (FST), especially in island and peripheral mainland populations, suggesting that the interplay between genetic drift and recombination causes highly heterogeneous differentiation landscapes. We also detected genomic outlier regions that were confined to one or more peripheral great tit populations, probably as a result of recent directional selection at the species' range edges. Haplotype-based measures of selection were related to recombination rate, albeit less strongly, and highlighted population-specific sweeps that likely resulted from positive selection. Our study highlights how comprehensive screens of genomic variation in wild organisms can provide unique insights into spatio-temporal evolutionary dynamics.

• Klíčová slova
• adaptation, birds, ecological genetics, genomics/proteomics, molecular evolution, population genetics – empirical,
• MeSH
• genetická variace * MeSH
• haplotypy genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• Passeriformes genetika   klasifikace   MeSH
• populační genetika metody   MeSH
• rekombinace genetická MeSH
• selekce (genetika) MeSH
• zpěvní ptáci * genetika   klasifikace   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH