Biology subjects

Smith, S. D.

Publications and source records attributed to Smith, S. D..

18 recordsLinked to original sources

bioRxiv2026

Effector-host networks in the barley powdery mildew pathosystem reveal significant targeting of ubiquitin-associated proteins and transcriptional regulators

- The ascomycete fungal pathogen Blumeria hordei (Bh) is predicted to secrete over 530 effector proteins to infect barley and cause powdery mildew disease, yet their individual and collective functions are largely unexplored. We used yeast two-hybrid next-generation interaction screening (Y2H-NGIS) to probe the host targets of 48 Bh candidate secreted effectors (CSEPs), including multiple AVRA effectors that are recognized by MLA nucleotide-binding leucine-rich repeat (NLR) receptors. - Y2H-NGIS and subsequent binary retesting identified 356 high-confidence protein-protein interactions (PPI) among Bh CSEPs, MLA NLR fragments, and barley proteins. We uncovered unique and shared host targets, including numerous proteins involved in ubiquitin-associated processes, gene expression, immune and kinase signaling, metabolism, and vesicle trafficking. - We identified a host protein (HvCAP2) that interacts with MLA and at least five Bh effectors, as well as additional effector-host PPI that correlate with loss of recognition of AVRA13 and AVRA6 by MLA13 and MLA6, respectively. - Results were integrated with an interolog-based barley interactome (HvInt) to assemble a host-pathogen network of 1248 proteins and 1701 interactions. This PPI resource can serve as a platform for functional investigations into the molecular basis of powdery mildew pathogenesis and host recognition.

plant biology↗

bioRxiv2025

Genetic Interaction of APOE-E-4 and PICALM rs3851179 is Associated With Dynamic Functional Connectivity in Healthy Middle-Aged Adults at Risk for Alzheimer's Disease

ObjectiveThis study investigates whether dynamic functional connectivity (dFC) dwell-time patterns derived from resting-state fMRI (rs-fMRI) can distinguish Alzheimers disease (AD) genetic risk profiles, specifically the APOE-{varepsilon}4 (A+) and PICALM rs3851179 (P+) variants, in cognitively healthy, middle-aged adults. ApproachWe estimated recurring dFC clusters from rs-fMRI data and quantified the dwell-time (total duration spent in specific connectivity states) for three cohorts: not-at-risk, A+P-, and A+P+. To evaluate the utility of these temporal features, group differences in dwell-time profiles were assessed, and logistic regression with permutation testing was employed to classify genotypes based on dFC patterns. Main resultsIndividuals in at-risk groups (A+P- and A+P+) exhibited significantly reduced dwell-time in left-hemisphere hubs compared to the not-at-risk group, aligning with known left-hemisphere vulnerability in early AD progression. The logistic regression models achieved above-chance discrimination of genotypes, with permutation tests confirming a significant trend when distinguishing not-at-risk individuals from the combined at-risk cohorts. SignificanceThese findings suggest that the temporal dFC features are sensitive to subtle functional brain alterations linked to AD genetic risk before clinical symptoms appear. Dwell-time features represent a promising physiological marker for early risk stratification and warrant further validation in larger longitudinal datasets. Our code is available at https://github.com/Shyamal-Dharia/APOE-PICALM-dFC-dwell-time.git.

neuroscience↗

bioRxiv2025

Late Cretaceous origins for major nightshade lineages from total evidence timetree analysis

Background and AimsThe timing of the radiation of nightshades (Solanaceae) has been contentious in the literature, with estimates of the crown age ranging from ca. 30 to 70 Mya (mid-Oligocene to late Cretaceous). The tempo of diversification of major lineages within the family (e.g., berries, tobaccos) has been equally challenging to resolve, in large part because of the paucity of fossil information. Recently described fossils present an opportunity to revisit the timing of nightshade diversification using more powerful model-based methods. Here, we simultaneously infer divergence times within Solanaceae and the placement of a select set of well-preserved and morphologically diverse fruit and seed fossils. MethodsWe assembled a family-wide morphological dataset, including 17 categorical and eight continuous characters, for 134 living and 14 fossil Solanaceae taxa, as well as sequence data for the extant taxa. We implemented a Bayesian total evidence dating analysis in RevBayes using (a time continuous and a time heterogeneous) fossilized birth-death model and models of character evolution for each type of data. Key ResultsThe origin of Solanaceae was [~]98 Mya, and the major splits were roughly three-fold older than previously estimated. Although the 14 fossil taxa were phylogenetically placed with different degrees of confidence, we identified a fruit fossil and a seed fossil whose affinities were strongly supported. Moreover, most of the fossils lacking a precise placement were nevertheless confidently inferred to belong to the large berry clade. ConclusionsOur study provides an example of how a sophisticated model used on a carefully assembled dataset can shed light on the timing of the evolution of a group, while accounting for phylogenetic uncertainty. The timetree we present here provides a temporal framework for further research, from comparative genomics and patterns of diversification to trait evolution and biogeography.

evolutionary biology↗

bioRxiv2025

Novel production of structurally diverse and sticky defense metabolites on wild tomatillo fruits

Plants have evolved a structurally diverse chemical repertoire to mediate various environmental interactions. Yet, little is known about the chemical complexity and metabolic pathways across many plant genera. Acylsugars are a class of specialized metabolites widely distributed across the Solanaceae that play a role in defense. Although acylsugars have been extensively characterized from leaf glandular trichomes, they have also been detected in other tissues. Nevertheless, acylsugar structures, biosynthesis, and functions outside of leaf trichomes remain unknown. Here, we performed tissue specific metabolomics across 29 Physalis species, an emerging model and crop genus closely related to important Solanum crops. Automated mass spec feature identification and library searches from surface extracts of leaf, calyx, and fruit tissues revealed metabolite diversity including putative metabolite classes of flavonoids, phenolics, and terpenoids. Acylsugar mass spec features were manually annotated, revealing at least 323 unique acylsugars - substantially expanding the known Physalis acylsugar diversity. Some, but not all, Physalis species accumulated acylsugars on the trichome-less fruit surface, and were as abundant or sometimes more abundant, in fruits than in leaves or calyces. Hierarchical clustering and phylogenetic tests indicated that species with similar acylsugar profiles do not cluster taxonomically. To determine the biochemical mechanism underlying acylsugar structural diversity, we characterized the first step of acylsugar biosynthesis, catalyzed by an acylsugar acyltransferase (ASAT). ASAT1s from three Physalis species displayed broad substrate preferences, which may explain the differences in acylsugar profiles. The diverse fruit-localized acylsugars across Physalis can inform engineering strategies for increased crop resilience.

plant biology↗

bioRxiv2025

A new phylogeny and phylogenetic classification for Solanaceae

Solanaceae are a globally distributed family of considerable economic importance. Recent phylogenetic work on various clades in the family has resulted in a plethora of names at various taxonomic levels. This results in a confusing set of names applied to clades at different ranks, and to the use of informal names that are often not accepted in online resources. To solve this problem, we present here a phylogenetic classification following the PhyloCode for the Solanaceae. Traditional taxon names previously recognized at the ranks of tribe, genus, and section were maintained when associated with clades. We base our clade definitions on a newly constructed phylogeny of the family using 10 plastid and nuclear markers with a broad sampling of 1,474 species, roughly half of the diversity of the family. We complement this marker-based analysis with a phylogenomic analysis of 110 taxa (including 97 of the 102 genera in the family) using the Angiosperms353 probe set. This pair of analyses produced highly concordant phylogenies and provides strong support for the clades included in the classification. In total, we propose and define rank-free names for 38 major clades, including 16 infrageneric taxa within the mega-diverse Solanum. This rank-free system intends to promote name stability as new data become available, avoiding name changes to well-known groups.

evolutionary biology↗

bioRxiv2025

Seed fossil record of Solanaceae revisited

The fossil record for Solanaceae has a complex taxonomic history, with many species originally described in the family being subsequently shown to belong in other plant families. In this work, we present an in-depth analysis of the nightshade seed fossil record, which corresponds to the largest amount of fossil material for the family despite having relatively few described taxa. We re-examined 110 fossil seeds previously assigned either to one of the six taxa or unplaced within the family. All fossils were imaged and measured for 14 discrete and continuous characters, and a subset of 22 well-preserved specimens was additionally subjected to micro-CT scanning. In parallel, we scored the same set of characters for seeds from 354 extant taxa of Solanaceae. We carried out a multivariate analysis of the combined extinct and extant dataset to visualize the placement of fossil seeds within Solanaceae seed morphospace. This analysis revealed a wide spread of fossils across morphospace, including a variety of shapes, sizes and testal wall features. For one fossil taxon (Hyoscyosperma daturoides Deanna & S.D.Sm. gen. et sp. nov.), the micro-CT images confirmed the presence of an elaiosome, otherwise only known in the family from the genus Datura L. Based on these analyses, we re-circumscribe three species and describe six new taxa (four in new genera), doubling the number of fossil seed species in the family. The broad geographic and stratigraphic distribution of these diverse taxa, from Eocene North America and Europe to Pleistocene Eurasia, support the notion that the Solanaceae is likely a family of a late Cretaceous origin that attained nearly a cosmopolitan distribution by the Eocene.

paleontology↗

bioRxiv2025

Polygenetic Determinants of Azole Resistance, Tolerance, and Heteroresistance in Candida albicans

Azole antifungals are widely used to treat Candida infections, yet therapeutic failures are common. In addition to resistance, fungal populations can exhibit tolerance and heteroresistance, subpopulation-driven drug responses that can contribute to treatment failure. Here, we performed a genome-wide association study (GWAS) on 557 genetically diverse C. albicans isolates to identify genetic loci associated with fluconazole susceptibility, tolerance, and heteroresistance. We uncovered a complex, polygenic architecture underlying all three traits, involving novel loci linked to stress responses, cell cycle, and genome integrity. Notably, canonical resistance genes were absent from our top associations, reflecting either their low frequency or lineage specificity. Functional validation of several candidate genes confirmed distinct genetic determinants for each drug response. Heritability estimates and conditional analyses revealed that susceptibility and heteroresistance are governed by partially overlapping but largely independent loci, with some genetic variants displaying opposing effects on different traits. This limited overlap suggests that each phenotype represents a distinct evolutionary strategy for drug evasion, which may not be simultaneously addressed by a single therapeutic approach. Our findings underscore the polygenic nature of adaptation to antifungal drugs and expand our understanding of drug response mechanisms in C. albicans. SIGNIFICANCEDespite advances in antifungal therapies, treatment failures in Candida albicans infections remain common and poorly understood. Standard clinical diagnostic tools rely on susceptibility testing to predict treatment outcomes, yet many treatment-refractory infections are caused by strains that appear susceptible in laboratory tests. This study provides the first genome-wide dissection of three distinct drug responses - susceptibility, tolerance, and heteroresistance - across a global population of C. albicans isolates. By identifying novel genetic contributors beyond canonical resistance genes, our findings shift the current paradigm toward a more nuanced, polygenic model of antifungal adaptation. These results underscore the importance of integrating tolerance and heteroresistance into clinical and research frameworks and point to new molecular pathways that could be leveraged to enhance antifungal strategies.

microbiology↗

bioRxiv2023

Transcriptome-based host epistasis and pathogen co-expression in barley-powdery mildew interactions

Mildew locus a (Mla) from the Triticeae grain crop barley (Hordeum vulgare L.) encodes a multi-allelic series of nucleotide-binding leucine-rich repeat (NLR) immune receptors. These variable NLRs recognize complementary secreted effectors from the powdery mildew fungus, Blumeria hordei (Bh), to block disease progression. We used a dynamic time-course transcriptome of barley infected with Bh to infer gene effects and epistatic relationships governed by the Mla6 NLR, two other host loci critical to the interaction, Blufensin1 (Bln1) and Required for Mla6 resistance3 (Rar3), and genes that interact with them. Bln1 is an R-gene independent regulator of immunity and the resistant bln1 mutant exhibits enhanced basal defense to compatible Bh. Rar3 is required for MLA6-mediated generation of H2O2 and the hypersensitive reaction; the rar3 mutant contains an in-frame Lys-Leu deletion in the SGT1-specific domain that compromises immunity by a subset of Mla alleles. Interactions of Mla6 and Bln1 resulted in symmetric, suppression and masked epistasis on the Bh-induced barley transcriptome. Likewise, dominant or equal effects were caused by Mla6 and Sgt1. Of a total of 468 barley NLRs, 366 were expressed in our dataset and 115 of those were grouped under different gene effect models, which localized to several chromosome hotspots. The corresponding Bh infection transcriptome was classified into nine co-expressed modules, linking differential expression with pathogen development. Expression of most of 517 Bh effectors exhibited dependence on disease phenotype and was associated with appressorial or haustorial structures, suggesting that disease is regulated by a host-pathogen intercommunication network that diversifies the response.

genetics↗

bioRxiv2023

THE POSSIBILITY OF AN EXTENSION OF CATARACT TREATMENT BEYOND EYE SURGERY: A NOVEL NON-INVASIVE PHOTOBLEACHING OF THE HUMAN LENS BY LED

As discussed below cataract is the world-leading cause of blindness and impaired vision with only eye surgery as a treatment. There is major requirement for an alternative which this research has provided via Genetically Modified pigs with natural cataract making live animal experiments of LED photobleaching successful monitored by fluorescence spectra. The latter were shown by EBS as spectrally identical in pigs and humans. EBS developed a miniature fluorescence spectrometer via tunable interference filters with fluorescence excited by an LED. A second LED in the blue/violet region provided a 20mW treatment beam which was shown to reverse the fluorescence signal and dramatically improve the transmission of pigs eyes. These results led to permission for early Human Trials. The results were judged by independent optometrists by LOCS and fluorescence in pigs and in Human Trials by LOCS and Visual Acuity. Adequate positive results have led to full length Human Trials being conducted in four European countries. Prospects of worldwide application have been therefore indicated.

biophysics↗

bioRxiv2023

Reassessing the origins of pathogenicity in Candida auris and relatives through phylogenomic analysis

Emerging fungal pathogens commonly originate from benign or non-pathogenic strains living in the natural environment. Assessing the evolutionary relationships between pathogenic and non-pathogenic species is one approach for tracing the origins of pathogenicity across species. The recently emerged human pathogen, Candida auris belongs to the Candida/Clavispora clade, a diverse group of 45 yeast species including human pathogens and environmental saprobes. C. auris is believed to have originated in the environment and recently transitioned to a human pathogen. We present a phylogenomic analysis of this clade aimed at testing for patterns implicated in the emergence of pathogenicity using an expanded sample of non-pathogenic strains and species. To build a robust framework for investigating these relationships, we developed a whole-genome sequence dataset of 108 isolates representing 18 species, including 4 newly sequenced species and 18 environmentally isolated strains. Our phylogeny, based on 619 orthologous genes, shows environmentally isolated species and strains interspersed with clinically isolated counterparts, rejecting the hypothesis of a single origin of pathogenicity within the lineage containing C. auris and its closest relatives. Our findings highlight the breadth of environments these yeasts inhabit, and imply, concerningly, that known pathogens could just as easily live outside the human body in diverse natural environments. Based on this result, we suggest that surveillance aimed at detecting emerging pathogens should expand to related environmentally-derived fungi with pathogenic potential. AUTHOR SUMMARYThe rapid rise in the number of fungal pathogens over the past few decades has been linked to climate change, globalization, intensive farming practices, and an increase in immunocompromised individuals. Candida auris is an example of a recently emerged fungal pathogen capable of causing severe disease and large outbreaks in vulnerable patient populations. The evolutionary origins of C. auris are poorly understood, however, they are essential to understanding how and when this pathogen emerged. In this study, we investigated relationships between a sample of pathogenic and non-pathogenic strains and species in the Candida/Clavispora clade, a group of 45 yeast species including human pathogens (including C. auris) and environmental saprobes. We used these relationships to test for patterns that might support differing pathogen emergence hypotheses. We found that the relationships between pathogens and non-pathogens suggest many transitions between humans and other environments, rather than a single origin of pathogenicity. It seems plausible that these pathogens, often found in harsh environmental conditions such as seawater, already possessed traits that make them suitable human pathogens, which are perpetuated by increased at-risk patient populations. We should, therefore, be vigilant in our surveillance for clinical isolation of yeasts belonging to this clade from humans.

evolutionary biology↗

bioRxiv2022

Flipped elevational pattern of pollination mode in tropical versus temperate Americas

AimAbiotic factors, such as temperature and precipitation, vary markedly along elevational gradients, and can in turn, shape key biotic interactions, such as herbivory and pollination. Despite the well-known effects of climatic conditions on pollinator activity and efficiency, we know little about the role of climate in pollinator shifts in animal-pollinated plants at broad geographic scales. Here we investigate patterns of altitudinal turnover in pollination mode across the Americas, with a focus on the most common pollinators (bees and hummingbirds). Specifically, we test Crudens classic hypothesis that plants are likely to shift to bird pollination at high elevations because endothermic pollinators are more reliable in cold and rainy conditions. LocationAmericas Time periodCurrent Major taxa studied2232 plant taxa from 26 clades MethodsWe collated information on pollination mode (1262 insect-pollinated, 970 vertebrate-pollinated) for the study taxa from the literature, and used GBIF occurrence data to estimate median distributions and bioclimatic attributes of each species. We used (phylogenetic) GLMMs to test for associations between pollination mode and ecogeographic variables. ResultsTo our surprise, we found flipped elevational patterns of insect- and vertebrate-pollination strategies across latitudes, with vertebrate pollination dominating at high elevations in the tropics, but not in temperate zones. We term this pattern the Tropical flip. We recovered a strong association of vertebrate-pollinated plants with moist, forested habitats across latitudes, while insect-pollinated plants were often found in cool and dry or warm and moist conditions. Main conclusionsAltitudinal gradients in temperature may not serve as a universal explanation for shifts among endothermic insect and ectothermic vertebrate pollination. Instead, strong abiotic niche differentiation among insect- and vertebrate-pollinated plants, along with competition for pollination niche space, has likely shaped the tropical flip.

ecology↗

bioRxiv2021

Diversity of Antibiotic Resistance genes and Transfer Elements-Quantitative Monitoring (DARTE-QM): a method for detection of antimicrobial resistance in environmental samples

Effective monitoring of antibiotic resistance genes and their dissemination in environmental ecosystems has been hindered by the cost and efficiency of methods available for the task. We developed a method entitled the Diversity of Antibiotic Resistance genes and Transfer Elements-Quantitative Monitoring (DARTE-QM), a system implementing high-throughput sequencing to simultaneously sequence thousands of antibiotic resistant genes representing a full-spectrum of antibiotic resistance classes commonly seen in environmental systems. In this study, we demonstrated DARTE-QM by screening 662 antibiotic resistance genes within environmental samples originated from manure, soil, and animal feces, in addition to a mock-community used as a control to test performance. DARTE-QM offers a new approach to studying antibiotic resistance in environmental microbiomes, showing advantages in efficiency and the ability to scale for many samples. This method provides a means of data acquisition that will alleviate the obstacles that many researchers in this area currently face.

microbiology↗

bioRxiv2020

Structure and contingency determine mutational hotspots for flower color evolution

Evolutionary genetic studies have uncovered abundant evidence for genomic hotspots of phenotypic evolution, as well as biased patterns of mutations at those loci. However, the theoretical basis for this concentration of particular types of mutations at particular loci remains largely unexplored. In addition, historical contingency is known to play a major role in evolutionary trajectories, but has not been reconciled with the existence of such hotspots. For example, do the appearance of hotspots and the fixation of different types of mutations at those loci depend on the starting state and/or on the nature and direction of selection? Here we use a computational approach to examine these questions, focusing the anthocyanin pigmentation pathway, which has been extensively studied in the context of flower color transitions. We investigate two transitions that are common in nature, the transition from blue to purple pigmentation and from purple to red pigmentation. Both sets of simulated transitions occur with a small number of mutations at just four loci and show strikingly similar peaked shapes of evolutionary trajectories, with the mutations of largest effect occurring early but not first. Nevertheless, the types of mutations (biochemical vs. regulatory) as well as their direction and magnitude are contingent on the particular transition. These simulated color transitions largely mirror findings from natural flower color transitions, which are known to occur via repeated changes at a few hotspot loci. Still, some types of mutations observed in our simulated color evolution are rarely observed in nature, suggesting that pleiotropic effects further limit the trajectories between color phenotypes. Overall, our results indicate that the branching structure of the pathway leads to a predictable concentration of evolutionary change at hotspot loci, but the types of mutations at these loci and their order is contingent on the evolutionary context.

evolutionary biology↗

bioRxiv2020

Phylogeny and Biogeography of South American Marsh Pitcher Plant Genus Heliamphora (Sarraceniaceae) Endemic to the Guiana Highlands

Heliamphora is a genus of carnivorous pitcher plants endemic to the Guiana Highlands with fragmented distributions. We presented a well resolved, time-calibrated, and nearly comprehensive Heliamphora phylogeny estimated using Bayesian inference and maximum likelihood based on nuclear genes (26S, ITS, and PHYC) and secondary calibration. We used stochastic mapping to infer ancestral states of morphological characters and ecological traits. Our ancestral state estimations revealed that the pitcher drainage structures characteristic of the genus transformed from a hole to a slit in single clade, while other features (scape pubescence and hammock-like growth) have been gained and lost multiple times. Habitat was similarly labile in Heliamphora, with multiple transitions from the ancestral highland habitats into the lowlands. Using Mantel test, we found closely related species tend to be geographically closely distributed. Placing our phylogeny in a historical context, major clades likely emerged through both vicariance and dispersal during Miocene with more recent diversification driven by vertical displacement during the Pleistocene glacial-interglacial thermal oscillations. Despite the dynamic climatic history experienced by Heliamphora, the temperature changes brought by global warming pose a significant threat, particularly for those species at the highest elevations.

evolutionary biology↗

bioRxiv2019

Computational modeling of anthocyanin pathway evolution

Alteration of metabolic pathways is a common mechanism underlying the evolution of new phenotypes. Flower color is a striking example of the importance of metabolic evolution in a complex phenotype, wherein shifts in the activity of the underlying pathway lead to a wide range of pigments. Although experimental work has identified common classes of mutations responsible for transitions among colors, we lack a unifying model that relates pathway function and activity to the evolution of distinct pigment phenotypes. One challenge in creating such a model is the branching structure of pigment pathways, which may lead to evolutionary trade-offs due to competition for shared substrates. In order to predict the effects of shifts in enzyme function and activity on pigment production, we created a simple kinetic model of a major plant pigmentation pathway: the anthocyanin pathway. This model describes the production of the three classes of blue, purple and red anthocyanin pigments, and accordingly, includes multiple branches and substrate competition. We first studied the general behavior of this model using a realistic, functional set of parameters. We then stochastically evolved the pathway toward a defined optimum and analyzed the patterns of fixed mutations. This approach allowed us to quantify the probability density of trajectories through pathway state space and identify the types and number of changes. Finally, we examined whether the observed trajectories and constraints align with experimental observations, i.e., the predominance of mutations which change color by altering the function of branching genes in the pathway. These analyses provide a theoretical framework that can be used to predict the consequences of new mutations in terms of both pigment phenotypes and pleiotropic effects.

evolutionary biology↗

bioRxiv2018

Repeated evolution of a morphological novelty: a phylogenetic analysis of the inflated fruiting calyx in the Physalideae tribe (Solanaceae)

PREMISE OF THE STUDYThe evolution of novel fruit morphologies has been integral to the success of angiosperms. The inflated fruiting calyx, in which the balloon-like calyx swells to completely surround the fruit, has evolved repeatedly across angiosperms and is postulated to aid in protection and dispersal. Here we investigate the evolution of this trait in the tomatillos and their allies (Physalideae, Solanaceae), using a newly estimated phylogeny and a suite of comparative methods to infer evolutionary gains and losses.\n\nMETHODSThe Physalideae phylogeny was estimated using DNA sequences from four regions (ITS, LEAFY, trnL-F, waxy) using maximum likelihood and Bayesian Inference. Maximum likelihood model selection was used to determine the best fitting model of trait evolution. Using this model, we estimated ancestral states along with the numbers of gains and losses of fruiting calyx accrescence and inflation with Bayesian stochastic mapping. Also, phylogenetic signal in calyx morphology was examined with two metrics (parsimony score and Fritz and Purvis D).\n\nKEY RESULTSThe well resolved phylogeny points to multiple taxa in need of revision, including the eight genera that are non-monophyletic as presently circumscribed. Model fitting indicated that calyx evolution has proceeded in stepwise fashion, from non-accrescent, to accrescent, to inflated. Moreover, these transitions appear to be largely irreversible. Among the 215 sampled Physalideae, we inferred 24 gains of fruiting calyx accrescence, 24 subsequent transitions to a fully inflated calyx and only two reversals. A median of 50 shifts were estimated in total across the clade from the ancestral non-accrescent calyx. Nonetheless, fruiting calyx accrescence and inflation show strong phylogenetic signal.\n\nCONCLUSIONSOur phylogeny greatly improves the resolution of Physalideae and highlights the need for taxonomic work. The analyses of trait evolution reveal that the inflated fruiting calyx has evolved many times and that the trajectory towards this phenotype is generally stepwise and directional. These results provide a strong foundation for studying the genetic and developmental mechanisms responsible for the repeated origins of this charismatic fruit trait.

evolutionary biology↗

bioRxiv2018

Genome Wide Association Scan identifies new variants associated with a cognitive predictor of dyslexia.

Developmental dyslexia (DD) is one of the most prevalent learning disorders among children and is characterized by deficits in different cognitive skills, including reading, spelling, short term memory and others. To help unravel the genetic basis of these skills, we conducted a Genome Wide Association Study (GWAS), including nine cohorts of reading-impaired and typically developing children of European ancestry, recruited across different countries (N=2,562-3,468).\n\nWe observed a genome-wide significant effect (p<1x10-8) on rapid automatized naming of letters (RANlet) for variants on 18q12.2 within MIR924HG (micro-RNA 924 host gene; p = 4.73x10-9), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; p = 2.25 x10-8). RAN represents one of the best universal predictors of reading fluency across orthographies and linkage to RAN has been previously reported within CELF4 (18q12.2), a gene highly expressed in the fetal brain which is co-expressed with NKAIN3 and predicted to be a target of MIR924. These findings suggest new candidate DD susceptibility genes and provide insights into the genetics and neurobiology of dyslexia.

genomics↗

bioRxiv2017

Multivariate genome-wide association study of rapid automatized naming and rapid alternating stimulus in Hispanic and African American youth.

Reading disability is a complex neurodevelopmental disorder that is characterized by difficulties in reading despite educational opportunity and normal intelligence. Performance on rapid automatized naming (RAN) and rapid alternating stimulus (RAS) tests gives a reliable predictor of reading outcome. These tasks involve the integration of different neural and cognitive processes required in a mature reading brain. Most studies examining the genetic factors that contribute to RAN and RAS performance have focused on pedigree-based analyses in samples of European descent, with limited representation of groups with Hispanic or African ancestry. In the present study, we conducted a multivariate genome-wide association analysis to identify shared genetic factors that contribute to performance across RAN Objects, RAN Letters, and RAS Letters/Numbers in a sample of Hispanic and African American youth (n=1,331). We then tested whether these factors also contribute to variance in reading fluency and word reading. Genome-wide significant, pleiotropic, effects across RAN Objects, RAN Letters, and RAS Letters/Numbers were observed for SNPs located on chromosome 10q23.31 (rs1555839, multivariate association, p=2.23 x 10-8), which also showed significant association with reading fluency and word reading performance (p <0.001). Bioinformatic analysis of this region using epigenetic data from the NIH Roadmap Epigenomics Mapping Consortium indicates active transcription of the gene RNLS in the brain. Neuroimaging genetic analysis of fourteen cortical regions in an independent sample of typically developing children across multiple ethnicities (n=690) showed that rs1555839 was associated with variation in volume of the right inferior parietal cortex--a region of the brain that processes numerical information and has been implicated in reading disability. This study provides support for a novel locus on chromosome 10q23.31 associated with RAN, RAS, and reading-related performance.\n\nAUTHOR SUMMARYReading disability has a strong genetic component that is explained by multiple genes and genetic factors. The complex genetic architecture along with diverse cognitive impairments associated with reading disability, poses challenges in identifying novel genes and variants that confer risk. One method to begin parsing genetic and neurobiological mechanisms that contribute to reading disability is to take advantage of the high correlation among reading-related cognitive traits like rapid automatized naming (RAN) and rapid alternating stimulus (RAS) to identify shared genetic factors that contribute to common biological mechanisms. In the present study, we used a multivariate genome-wide analysis approach that identified a region of chromosome 10q23.31 associated with variation in RAN Objects, RAN Letters, and RAS Letters/Numbers performance in a sample of 1,331 Hispanic and African American youth in the Genes, Reading, and Dyslexia (GRaD) Study. Genetic variants in this region were also associated with reading fluency in GRaD, and differences in brain structures implicated in reading disability in a separate sample of 690 children. The gene, RNLS, is located within the implicated region of chromosome 10q23.31 and plays a role in breaking down a class of chemical messengers known to affect attention, learning, and memory in the brain. These findings provide a basis to inform our understanding of the biological basis of reading disability.

genetics↗