Identification and Phenotypic Characterization of Hsp90 Phosphorylation Sites That Modulate Virulence Traits in the Major Human Fungal Pathogen .

The highly conserved, ubiquitous molecular chaperone Hsp90 is a key regulator of cellular proteostasis and environmental stress responses. In human pathogenic fungi, which kill more than 1.6 million patients each year worldwide, Hsp90 governs cellular morphogenesis, drug resistance, and virulence.

Tobacco Hornworm () caterpillars as a novel host model for the study of fungal virulence and drug efficacy.

The two leading yeast pathogens of humans, and , cause systemic infections in >1.4 million patients worldwide with mortality rates approaching 75%. It is thus imperative to study fungal virulence mechanisms, efficacy of antifungal drugs, and host response pathways.

Cis-effects on gene expression in the human prenatal brain associated with genetic risk for neuropsychiatric disorders.

The majority of common risk alleles identified for neuropsychiatric disorders reside in noncoding regions of the genome and are therefore likely to impact gene regulation. However, the genes that are primarily affected and the nature and developmental timing of these effects remain unclear. Given the hypothesized role for early neurodevelopmental processes in these conditions, we here define genetic predictors of gene expression in the human fetal brain with which we perform transcriptome-wide association studies (TWASs) of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, bipolar disorder, major depressive disorder, and schizophrenia.

Novel Insight Into the Etiology of Autism Spectrum Disorder Gained by Integrating Expression Data With Genome-wide Association Statistics.

Background: A recent genome-wide association study (GWAS) of autism spectrum disorder (ASD) (n = 18,381, n = 27,969) has provided novel opportunities for investigating the etiology of ASD. Here, we integrate the ASD GWAS summary statistics with summary-level gene expression data to infer differential gene expression in ASD, an approach called transcriptome-wide association study (TWAS).

Methods: Using FUSION software, ASD GWAS summary statistics were integrated with predictors of gene expression from 16 human datasets, including adult and fetal brains.

Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders.

Background: Genetic influences on gene expression in the human fetal brain plausibly impact upon a variety of postnatal brain-related traits, including susceptibility to neuropsychiatric disorders. However, to date, there have been no studies that have mapped genome-wide expression quantitative trait loci (eQTL) specifically in the human prenatal brain.

Results: We performed deep RNA sequencing and genome-wide genotyping on a unique collection of 120 human brains from the second trimester of gestation to provide the first eQTL dataset derived exclusively from the human fetal brain.

Light-induced dynamic structural color by intracellular 3D photonic crystals in brown algae.

Natural photonic crystals are responsible for strong reflectance at selective wavelengths in different natural systems. We demonstrate that intracellular opal-like photonic crystals formed from lipids within photosynthetic cells produce vivid structural color in the alga . The reflectance of the opaline vesicles is dynamically responsive to environmental illumination.

Genomic and Gene-Expression Comparisons among Phage-Resistant Type-IV Pilus Mutants of Pseudomonas syringae pathovar phaseolicola.

Pseudomonas syringae pv. phaseolicola (Pph) is a significant bacterial pathogen of agricultural crops, and phage Φ6 and other members of the dsRNA virus family Cystoviridae undergo lytic (virulent) infection of Pph, using the type IV pilus as the initial site of cellular attachment. Despite the popularity of Pph/phage Φ6 as a model system in evolutionary biology, Pph resistance to phage Φ6 remains poorly characterized.

Dispersal analysis of three species based on landscape genetics data.

Lichens can either disperse sexually through fungal spores or asexually through vegetative propagules and fragmentation. Understanding how genetic variation in lichens is distributed across a landscape can be useful to infer dispersal and establishment events in space and time as well as the conditions needed for this establishment. Most studies have sampled lichens across large spatial distances on the order of hundreds of kilometers, while here we sequence the internal transcribed spacer (ITS) for 113 samples of three species sampling at a variety of small spatial scales.

Assessing population structure and host specialization in lichenized cyanobacteria.

Coevolutionary theory predicts that the distribution of obligately symbiotic organisms will be determined by the dispersal ability and ecological range of both partners. We examined this prediction for lichen-forming fungi that form obligate symbioses with cyanobacteria. We compared genotypes of both partners of 250 lichens collected at multiple spatial scales in British Columbia, Canada.

Extensive remodeling of the Pseudomonas syringae pv. avellanae type III secretome associated with two independent host shifts onto hazelnut.

Background: Hazelnut (Corylus avellana) decline disease in Greece and Italy is caused by the convergent evolution of two distantly related lineages of Pseudomonas syringae pv. avellanae (Pav). We sequenced the genomes of three Pav isolates to determine if their convergent virulence phenotype had a common genetic basis due to either genetic exchange between lineages or parallel evolution.

Use of low-coverage, large-insert, short-read data for rapid and accurate generation of enhanced-quality draft Pseudomonas genome sequences.

Next-generation genomic technology has both greatly accelerated the pace of genome research as well as increased our reliance on draft genome sequences. While groups such as the Genomics Standards Consortium have made strong efforts to promote genome standards there is a still a general lack of uniformity among published draft genomes, leading to challenges for downstream comparative analyses. This lack of uniformity is a particular problem when using standard draft genomes that frequently have large numbers of low-quality sequencing tracts.

HopAS1 recognition significantly contributes to Arabidopsis nonhost resistance to Pseudomonas syringae pathogens.

• Plant immunity is activated by sensing either conserved microbial signatures, called pathogen/microbe-associated molecular patterns (P/MAMPs), or specific effectors secreted by pathogens. However, it is not known why most microbes are nonpathogenic in most plant species. • Nonhost resistance (NHR) consists of multiple layers of innate immunity and protects plants from the vast majority of potentially pathogenic microbes.

Evolution of plant pathogenesis in Pseudomonas syringae: a genomics perspective.

The phytopathogenic bacterium Pseudomonas syringae causes serious diseases in a wide range of important crop plants, with recent severe outbreaks on the New Zealand kiwifruit crop and among British horse chestnut trees. Next-generation genome sequencing of over 25 new strains has greatly broadened our understanding of how this species adapts to a diverse range of plant hosts. Not unexpectedly, the genomes were found to be highly dynamic, and extensive polymorphism was found in the distribution of type III secreted effectors (T3SEs) and other virulence-associated genes, even among strains within the same pathovar.

Next-generation genomics of Pseudomonas syringae.

The first wave of Pseudomonas syringae next-generation genomic studies has revealed insights into host-specific virulence and immunity, genome dynamics and evolution, and genetic and metabolic specialization. These studies have further enhanced our understanding of type III effector diversity, identified an atypical type III secretion system (T3SS) in a new clade of nonpathogenic P. syringae, identified metabolic pathways common to pathogens of woody hosts and revealed extensive genomic diversity among strains that infect common hosts.

Multiple origins of high reciprocal symbiotic specificity at an intercontinental spatial scale among gelatinous lichens (Collemataceae, Lecanoromycetes).

Because the number of fungal species (mycobionts) exceeds the number of algae and cyanobacteria (photobionts) found in lichens by more than two orders of magnitude, reciprocal one-to-one specificity between one fungal species and one photobiont across their entire distribution is not expected in this symbiotic system, and has not previously been observed. The specificity of the cyanobacterium Nostoc found in lichens was evaluated at a broad geographical scale within one of the main families of lichen-forming fungi (Collemataceae) that associate exclusively with this photobiont. A phylogenetic study was conducted using rbcLXS sequences from Nostoc sampled from 79 thalli (representing 24 species within the Collemataceae), and 163 Nostoc sequences gathered from GenBank.

Assessing reproductive isolation in highly diverse communities of the lichen-forming fungal genus peltigera.

The lichen-forming fungal genus Peltigera includes a number of species that are extremely widespread, both geographically and ecologically. However, morphological variability has lead to doubts about the distinctness of some species, and it has been suggested that hybridization is common in nature. We examined species boundaries by looking for evidence of hybridization and gene flow among seven described species collected at five sites in British Columbia, Canada.

Moths that vector a plant pathogen also transport endophytic fungi and mycoparasitic antagonists.

Claviceps paspali, a common fungal pathogen of Paspalum grasses, attracts moth vectors by producing sugary exudates in the grass florets it infects. These exudates also support mycoparasitic Fusarium species that may negatively influence C. paspali fitness.

Correlated evolution of self-incompatibility and clonal reproduction in Solanum (Solanaceae).

It has been suggested that clonality provides reproductive assurance in cross-fertilizing species subject to pollen limitation, relieving one of the main selective pressures favoring the evolution of self-fertilization. According to this hypothesis, cross-fertilizing species subject to pollen limitation should often be clonal. Here, we investigated the association between clonality and a genetic mechanism enforcing outcrossing, self-incompatibility, in Solanum (Solanaceae).

Fungal community analysis by large-scale sequencing of environmental samples.

Fungi are an important and diverse component of soil communities, but these communities have proven difficult to study in conventional biotic surveys. We evaluated soil fungal diversity at two sites in a temperate forest using direct isolation of small-subunit and internal transcribed spacer (ITS) rRNA genes by PCR and high-throughput sequencing of cloned fragments. We identified 412 sequence types from 863 fungal ITS sequences, as well as 112 ITS sequences from other eukaryotic microorganisms.

Repeated evolution of net venation and fleshy fruits among monocots in shaded habitats confirms a priori predictions: evidence from an ndhF phylogeny.

We present a well-resolved, highly inclusive phylogeny for monocots, based on ndhF sequence variation, and use it to test a priori hypotheses that net venation and vertebrate-dispersed fleshy fruits should undergo concerted convergence, representing independent but often concurrent adaptations to shaded conditions. Our data demonstrate that net venation arose at least 26 times and was lost eight times over the past 90 million years; fleshy fruits arose at least 21 times and disappeared 11 times. Both traits show a highly significant pattern of concerted convergence (p<10(-9)), arising 16 times and disappearing four times in tandem.

Inference of higher-order relationships in the cycads from a large chloroplast data set.

We investigated higher-order relationships in the cycads, an ancient group of seed-bearing plants, by examining a large portion of the chloroplast genome from seven species chosen to exemplify our current understanding of taxonomic diversity in the order. The regions considered span approximately 13.5 kb of unaligned data per taxon, and comprise a diverse range of coding sequences, introns and intergenic spacers dispersed throughout the plastid genome.