Parallel evolution is common in nature and provides one of the most compelling examples of rapid environmental adaptation. In contrast to the recent burst of studies addressing genomic basis of parallel evolution, integrative studies linking genomic and phenotypic parallelism are scarce. Edaphic islands of toxic serpentine soils provide ideal systems for studying rapid parallel adaptation in plants, imposing strong, spatially replicated selection on recently diverged populations. We leveraged threefold independent serpentine adaptation of Arabidopsis arenosa and combined reciprocal transplants, ion uptake phenotyping, and available genome-wide polymorphisms to test if parallelism is manifested to a similar extent at both genomic and phenotypic levels. We found pervasive phenotypic parallelism in functional traits yet with varying magnitude of fitness differences that was congruent with neutral genetic differentiation between populations. Limited costs of serpentine adaptation suggest absence of soil-driven trade-offs. On the other hand, the genomic parallelism at the gene level was significant, although relatively minor. Therefore, the similarly modified phenotypes, for example, of ion uptake arose possibly by selection on different loci in similar functional pathways. In summary, we bring evidence for the important role of genetic redundancy in rapid adaptation involving traits with polygenic architecture.

• Klíčová slova
• Adaptation, Arabidopsis, genetic redundancy, natural selection, parallel evolution, reciprocal transplant,
• MeSH
• Arabidopsis * genetika   MeSH
• fenotyp MeSH
• fyziologická adaptace genetika   MeSH
• genomika MeSH
• půda MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• půda MeSH

Parallel evolution provides powerful natural experiments for studying repeatability of evolution and genomic basis of adaptation. Well-documented examples from plants are, however, still rare, as are inquiries of mechanisms driving convergence in some traits while divergence in others. Arabidopsis arenosa, a predominantly foothill species with scattered morphologically distinct alpine occurrences is a promising candidate. Yet, the hypothesis of parallelism remained untested. We sampled foothill and alpine populations in all regions known to harbor the alpine ecotype and used SNP genotyping to test for repeated alpine colonization. Then, we combined field surveys and a common garden experiment to quantify phenotypic parallelism. Genetic clustering by region but not elevation and coalescent simulations demonstrated parallel origin of alpine ecotype in four mountain regions. Alpine populations exhibited parallelism in height and floral traits which persisted after two generations in cultivation. In contrast, leaf traits were distinctive only in certain region(s), reflecting a mixture of plasticity and genetically determined non-parallelism. We demonstrate varying degrees and causes of parallelism and non-parallelism across populations and traits within a plant species. Parallel divergence along a sharp elevation gradient makes A. arenosa a promising candidate for studying genomic basis of adaptation.

• Klíčová slova
• Arabidopsis, adaptation, alpine environments, convergence, parallel evolution, phenotypic parallelism,
• Publikační typ
• časopisecké články MeSH

Parallel adaptation provides valuable insight into the predictability of evolutionary change through replicated natural experiments. A steadily increasing number of studies have demonstrated genomic parallelism, yet the magnitude of this parallelism varies depending on whether populations, species, or genera are compared. This led us to hypothesize that the magnitude of genomic parallelism scales with genetic divergence between lineages, but whether this is the case and the underlying evolutionary processes remain unknown. Here, we resequenced seven parallel lineages of two Arabidopsis species, which repeatedly adapted to challenging alpine environments. By combining genome-wide divergence scans with model-based approaches, we detected a suite of 151 genes that show parallel signatures of positive selection associated with alpine colonization, involved in response to cold, high radiation, short season, herbivores, and pathogens. We complemented these parallel candidates with published gene lists from five additional alpine Brassicaceae and tested our hypothesis on a broad scale spanning ∼0.02 to 18 My of divergence. Indeed, we found quantitatively variable genomic parallelism whose extent significantly decreased with increasing divergence between the compared lineages. We further modeled parallel evolution over the Arabidopsis candidate genes and showed that a decreasing probability of repeated selection on the same standing or introgressed alleles drives the observed pattern of divergence-dependent parallelism. We therefore conclude that genetic divergence between populations, species, and genera, affecting the pool of shared variants, is an important factor in the predictability of genome evolution.

• Klíčová slova
• Arabidopsis, alpine adaptation, evolution, genomics, parallelism,
• MeSH
• anotace sekvence MeSH
• Arabidopsis klasifikace   genetika   metabolismus   účinky záření   MeSH
• biologická evoluce * MeSH
• býložravci fyziologie   MeSH
• fyziologická adaptace genetika   MeSH
• fyziologický stres MeSH
• genetická variace * MeSH
• genetický drift MeSH
• genom rostlinný * MeSH
• genová introgrese MeSH
• genová ontologie MeSH
• ionizující záření MeSH
• modely genetické MeSH
• nízká teplota MeSH
• rostlinné proteiny genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• rostlinné proteiny MeSH

Kabuki syndrome is mainly caused by dominant de-novo pathogenic variants in the KMT2D and KDM6A genes. The clinical features of this syndrome are highly variable, making the diagnosis of Kabuki-like phenotypes difficult, even for experienced clinical geneticists. Herein we present molecular genetic findings of causal genetic variation using array comparative genome hybridization and a Mendeliome analysis, utilizing targeted exome analysis focusing on regions harboring rare disease-causing variants in Kabuki-like patients which remained KMT2D/KDM6A-negative. The aCGH analysis revealed a pathogenic CNV in the 14q11.2 region, while targeted exome sequencing revealed pathogenic variants in genes associated with intellectual disability (HUWE1, GRIN1), including a gene coding for mandibulofacial dysostosis with microcephaly (EFTUD2). Lower values of the MLL2-Kabuki phenotypic score are indicative of Kabuki-like phenotype (rather than true Kabuki syndrome), where aCGH and Mendeliome analyses have high diagnostic yield. Based on our findings we conclude that for new patients with Kabuki-like phenotypes it is possible to choose a specific molecular testing approach that has the highest detection rate for a given MLL2-Kabuki score, thus fostering more precise patient diagnosis and improved management in these genetically- and phenotypically heterogeneous clinical entities.

• Klíčová slova
• EFTUD2, GRIN1, HUWE1, Intellectual disability, KMT2D, Kabuki syndrome,
• MeSH
• dítě MeSH
• DNA vazebné proteiny genetika   MeSH
• elongační faktory genetika   MeSH
• exom MeSH
• fenotyp * MeSH
• genetická heterogenita * MeSH
• genotyp * MeSH
• histondemethylasy genetika   MeSH
• jaderné proteiny genetika   MeSH
• krevní nemoci diagnóza   genetika   patofyziologie   MeSH
• lidé MeSH
• lidské chromozomy, pár 14 MeSH
• malý jaderný ribonukleoprotein U5 genetika   MeSH
• mandibulofaciální dysostóza genetika   MeSH
• mentální retardace genetika   MeSH
• mikrocefalie genetika   MeSH
• mnohočetné abnormality diagnóza   genetika   patofyziologie   MeSH
• nádorové proteiny genetika   MeSH
• nádorové supresorové proteiny genetika   MeSH
• obličej abnormality   patofyziologie   MeSH
• předškolní dítě MeSH
• proteiny nervové tkáně genetika   MeSH
• receptory N-methyl-D-aspartátu genetika   MeSH
• srovnávací genomová hybridizace MeSH
• ubikvitinligasy genetika   MeSH
• vestibulární nemoci diagnóza   genetika   patofyziologie   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• EFTUD2 protein, human MeSH Prohlížeč
• elongační faktory MeSH
• GRIN1 protein, human MeSH Prohlížeč
• histondemethylasy MeSH
• HUWE1 protein, human MeSH Prohlížeč
• jaderné proteiny MeSH
• KDM6A protein, human MeSH Prohlížeč
• KMT2D protein, human MeSH Prohlížeč
• malý jaderný ribonukleoprotein U5 MeSH
• nádorové proteiny MeSH
• nádorové supresorové proteiny MeSH
• proteiny nervové tkáně MeSH
• receptory N-methyl-D-aspartátu MeSH
• ubikvitinligasy MeSH

Several hypotheses have been put forward to explain the evolution of prey specificity (stenophagy). Yet little light has so far been shed on the process of evolution of stenophagy in carnivorous predators. We performed a detailed analysis of a variety of trophic adaptations in one species. Our aim was to determine whether a specific form of stenophagy, myrmecophagy, has evolved from euryphagy via parallel changes in several traits from pre-existing characters. For that purpose, we studied the trophic niche and morphological, behavioural, venomic and physiological adaptations in a euryphagous spider, Selamia reticulata. It is a species that is branching off earlier in phylogeny than stenophagous ant-eating spiders of the genus Zodarion (both Zodariidae). The natural diet was wide and included ants. Laboratory feeding trials revealed versatile prey capture strategies that are effective on ants and other prey types. The performance of spiders on two different diets - ants only and mixed insects - failed to reveal differences in most fitness components (survival and developmental rate). However, the weight increase was significantly higher in spiders on the mixed diet. As a result, females on a mixed diet had higher fecundity and oviposited earlier. No differences were found in incubation period, hatching success or spiderling size. S. reticulata possesses a more diverse venom composition than Zodarion. Its venom is more effective for the immobilisation of beetle larvae than of ants. Comparative analysis of morphological traits related to myrmecophagy in the family Zodariidae revealed that their apomorphic states appeared gradually along the phylogeny to derived prey-specialised genera. Our results suggest that myrmecophagy has evolved gradually from the ancestral euryphagous strategy by integrating a series of trophic traits.

• MeSH
• biologická evoluce MeSH
• dieta MeSH
• druhová specificita MeSH
• Formicidae MeSH
• fyziologická adaptace MeSH
• genetická zdatnost MeSH
• pavoučí jedy chemie   MeSH
• pavouci anatomie a histologie   chemie   genetika   fyziologie   MeSH
• potravní řetězec MeSH
• predátorské chování MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• stárnutí MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• pavoučí jedy MeSH

The fungal genus Cryptococcus includes several life-threatening human pathogens as well as diverse saprobic species whose genome architecture, ecology, and evolutionary history remain less well characterized. Understanding how some lineages evolved into major pathogens remains a central challenge and may be advanced by comparisons with their nonpathogenic counterparts. Integrative approaches have become essential for delimiting species and reconstructing evolutionary relationships, particularly in lineages with cryptic diversity or extensive chromosomal rearrangements. Here, we formally characterize six Cryptococcus species representing distinct evolutionary lineages, comprising both newly discovered and previously recognized but unnamed taxa, through a combination of phylogenomic analyses, divergence metrics, chromosomal comparisons, mating assays, and phenotypic profiling. Among pathogenic taxa, we formally name Cryptococcus hyracis sp. nov., corresponding to the previously characterized VGV lineage within the C. gattii complex. In parallel, we describe five saprobic, nonpathogenic species isolated from fruit, soil, and bark beetle galleries, spanning four phylogenetic clades. We identify a strong ecological association with bark beetles for Cryptococcus porticicola sp. nov., the only newly described nonpathogenic species with multiple sequenced strains from diverse sites. In this species, we detect strain-level chromosomal variation and evidence of sexual reproduction, along with population-level signatures of recombination consistent with ongoing genetic exchange. Across the genus, chromosome-level comparisons reveal extensive structural variation, including species- and strain-specific rearrangements that may restrict gene flow. We also identify multiple instances of chromosome number reduction, often associated with centromere inactivation following interchromosomal rearrangements. Comparative metabolic profiling with Biolog phenotype microarrays reveals clade-level differentiation and distinct substrate preferences, which may reflect metabolic divergence and habitat-specific diversification. Notably, we confirm that thermotolerance is restricted to clinically relevant taxa. These findings refine the species-level taxonomy of Cryptococcus, broaden its known genomic and ecological diversity, and strengthen the framework for investigating speciation, adaptation, and the emergence of pathogenicity within the genus.

• Klíčová slova
• Fungal speciation, chromosome evolution, comparative genomics, digital DNA–DNA hybridization, human fungal pathogens, rRNA architecture,
• Publikační typ
• časopisecké články MeSH
• preprinty MeSH

Despite widespread variability and redundancy abounding animal immunity, little is currently known about the rate of evolutionary convergence (functionally analogous traits not inherited from a common ancestor) in host molecular adaptations to parasite selective pressures. Toll-like receptors (TLRs) provide the molecular interface allowing hosts to recognize pathogenic structures and trigger early danger signals initiating an immune response. Using a novel combination of bioinformatic approaches, here we explore genetic variation in ligand-binding regions of bacteria-sensing TLR4 and TLR5 in 29 species belonging to the tit family of passerine birds (Aves: Paridae). Three out of the four consensual positively selected sites in TLR4 and six out of 14 positively selected positions in TLR5 were located on the receptor surface near the functionally important sites, and based on the phylogenetic pattern evolved in a convergent (parallel) manner. This type of evolution was also seen at one N-glycosylation site and two positively selected phosphorylation sites, providing the first evidence of convergence in post-translational modifications in evolutionary immunology. Finally, the overall mismatch between phylogeny and the clustering of surface charge distribution demonstrates that convergence is common in overall TLR4 and TLR5 molecular phenotypes involved in ligand binding. Our analysis did not reveal any broad ecological traits explaining the convergence observed in electrostatic potentials, suggesting that information on microbial symbionts may be needed to explain TLR evolution. Adopting state-of-the-art predictive structural bionformatics, we have outlined a new broadly applicable methodological approach to estimate the functional significance of positively selected variation and test for the adaptive molecular convergence in protein-coding polymorphisms.

• Klíčová slova
• avian immunogenetics, innate immune genes, molecular co-evolution, pattern recognition receptors, post-translational modifications, surface electrostatic potential,
• MeSH
• fenotyp MeSH
• fylogeneze MeSH
• molekulární evoluce * MeSH
• Passeriformes * MeSH
• přirozená imunita genetika   MeSH
• selekce (genetika) MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disease resulting from pathogenic variants in the GLA gene coding α-galactosidase A (AGAL) and cleaving terminal alpha-linked galactose. Globotriaosylceramide (Gb3) is the predominantly accumulated sphingolipid. Gb3, deacylated-Gb3 (lysoGb3), and methylated-Gb3 (metGb3) have been suggested as FD biomarkers. MATERIALS AND METHODS: We developed a novel LC-MS/MS method for assessing lysoGb3 levels in plasma and Gb3 and metGb3 in urine and tested 62 FD patients, 34 patients with GLA variants of unknown significance (VUS) and 59 healthy controls. AGAL activity in white blood cells (WBCs) and plasma was evaluated in parallel. RESULTS: In males, lysoGb3 concentrations in plasma separated classic and late-onset FD patients from each other and from individuals carrying GLA VUS and healthy controls. Calculating AGAL activity/plasmatic lysoGb3 ratio allowed to correctly categorize all females with classic and majority of patients with late-onset FD phenotypes. Correlation of AGAL activity in WBCS with lipid biomarkers identified threshold activity values under which the biomarkers' concentrations increase. CONCLUSION: We developed a novel simplified LC-MS/MS method for quantitation of plasma lysoGb3. AGAL activity/plasma lysoGb3 ratio was identified as the best predictor for FD. AGAL activity correlated with plasma lysoGb3 and corresponded to individual FD phenotypes.

• Klíčová slova
• Diagnostics, Fabry disease, Globotriaosylsphingosine, Lysosomal storage, Mass spectrometry, Phenotype,
• MeSH
• alfa-galaktosidasa genetika   metabolismus   MeSH
• biologické markery krev   MeSH
• chromatografie kapalinová MeSH
• dospělí MeSH
• Fabryho nemoc * krev   diagnóza   moč   MeSH
• fenotyp MeSH
• glykolipidy krev   moč   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři MeSH
• sfingolipidy * krev   MeSH
• tandemová hmotnostní spektrometrie * MeSH
• trihexosylceramidy metabolismus   krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfa-galaktosidasa MeSH
• biologické markery MeSH
• globotriaosyl lysosphingolipid MeSH Prohlížeč
• globotriaosylceramide MeSH Prohlížeč
• glykolipidy MeSH
• sfingolipidy * MeSH
• trihexosylceramidy MeSH

Mass releases of sterilized male insects, in the frame of sterile insect technique programs, have helped suppress insect pest populations since the 1950s. In the major horticultural pests Bactrocera dorsalis, Ceratitis capitata, and Zeugodacus cucurbitae, a key phenotype white pupae (wp) has been used for decades to selectively remove females before releases, yet the gene responsible remained unknown. Here, we use classical and modern genetic approaches to identify and functionally characterize causal wp- mutations in these distantly related fruit fly species. We find that the wp phenotype is produced by parallel mutations in a single, conserved gene. CRISPR/Cas9-mediated knockout of the wp gene leads to the rapid generation of white pupae strains in C. capitata and B. tryoni. The conserved phenotype and independent nature of wp- mutations suggest this technique can provide a generic approach to produce sexing strains in other major medical and agricultural insect pests.

• MeSH
• biologická kontrola škůdců metody   MeSH
• Ceratitis capitata genetika   MeSH
• CRISPR-Cas systémy MeSH
• fenotyp MeSH
• fertilita genetika   MeSH
• genom hmyzu genetika   MeSH
• hmyzí proteiny genetika   MeSH
• kukla genetika   MeSH
• mutace * MeSH
• rozmnožování genetika   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• Tephritidae klasifikace   genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• hmyzí proteiny MeSH

Relative contributions of pre-existing vs de novo genomic variation to adaptation are poorly understood, especially in polyploid organisms. We assess this in high resolution using autotetraploid Arabidopsis arenosa, which repeatedly adapted to toxic serpentine soils that exhibit skewed elemental profiles. Leveraging a fivefold replicated serpentine invasion, we assess selection on SNPs and structural variants (TEs) in 78 resequenced individuals and discover significant parallelism in candidate genes involved in ion homeostasis. We further model parallel selection and infer repeated sweeps on a shared pool of variants in nearly all these loci, supporting theoretical expectations. A single striking exception is represented by TWO PORE CHANNEL 1, which exhibits convergent evolution from independent de novo mutations at an identical, otherwise conserved site at the calcium channel selectivity gate. Taken together, this suggests that polyploid populations can rapidly adapt to environmental extremes, calling on both pre-existing variation and novel polymorphisms.

• MeSH
• alely * MeSH
• Arabidopsis účinky léků   genetika   MeSH
• fyziologická adaptace účinky léků   genetika   MeSH
• genom rostlinný * MeSH
• jednonukleotidový polymorfismus MeSH
• mutace MeSH
• polyploidie * MeSH
• proteiny huseníčku genetika   metabolismus   MeSH
• půda chemie   MeSH
• sekologanin-tryptaminové alkaloidy metabolismus   MeSH
• vápníkové kanály metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• proteiny huseníčku MeSH
• půda MeSH
• sekologanin-tryptaminové alkaloidy MeSH
• serpentine (alkaloid) MeSH Prohlížeč
• TPC1 protein, Arabidopsis MeSH Prohlížeč
• vápníkové kanály MeSH