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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2016

The Quick and the Dead: Microbial Demography at the Yeast Thermal Limit

The niche of microorganisms is determined by where their populations can expand. Populations can fail to grow because of high death or low birth rates, but these are challenging to measure in microorganisms. We developed a novel technique that enables single cell measurement of age-structured birth and death rates in the budding yeast, Saccharomyces cerevisiae, and used this method to study responses to heat stress in a genetically diverse panel of strains. We find that individual cells show significant heterogeneity in their rates of birth and death during heat stress. Genotype-by-environment effects on processes that regulate asymmetric cell division contribute to this heterogeneity. These lead to either premature senescence or early life mortality during heat stress, and we find that a mitochondrial inheritance defect explains the early life mortality phenotype of one of the strains we studied. This study demonstrates how the interplay of physiology, genetic variation, and environmental variables influences where microbial populations survive and flourish.

Microbiology↗

bioRxiv2016

Dopaminergic neurons modulate locomotion in Caenorhabditis elegans

Adaptation in the sensory-mechanical loop during locomotion is a powerful mechanism that allows organisms to survive in different conditions and environments. Motile animals need to alter motion patterns in different environments. For example, crocodiles and other animals can walk on solid ground but switch to swimming in water beds. The nematode Caenorhabditis elegans also shows adaptability by employing thrashing behaviour in low viscosity media and crawling in high viscosity media. The mechanism that enables this adaptability is an active area of research. It has been attributed previously to neuro-modulation by dopamine and serotonin.\n\nThe aim of this study is to physiologically investigate the neuronal mechanisms of modulation of locomotion by dopamine. The results suggest that the mechanosensory properties of the dopaminergic neurons PDE are not limited to touch sensation, but to surrounding environment resistance as well. The significance of such characterization is improving our understanding of dopamine gait switching which gets impaired in Parkinsons disease.

Neuroscience↗

bioRxiv2016

Distinct combinations of variant ionotropic glutamate receptors mediate thermosensation and hygrosensation in Drosophila

Ionotropic Receptors (IRs) are a large subfamily of variant ionotropic glutamate receptors present across Protostomia. While these receptors are most extensively studied for their roles in chemosensory detection in insects, recent work has implicated two family members, IR21a and IR25a, in thermosensation in Drosophila. Here we characterize one of the most deeply conserved receptors, IR93a, and show that it is co-expressed and functions with IR21a and IR25a to mediate physiological and behavioral responses to cool temperatures. IR93a is also co-expressed with IR25a and a distinct receptor, IR40a, in a discrete population of sensory neurons in the sacculus, a multi-chambered pocket within the antenna. We demonstrate that this combination of receptors is important for neuronal responses to dry air and behavioral discrimination of humidity differences. Our results identify IR93a as a common component of molecularly and cellularly distinct IR pathways underlying thermosensation and hygrosensation in insects.

Neuroscience↗

bioRxiv2016

Dnmts mediate neural processing after odor learning in the honeybee

DNA methyltransferases (Dnmts)-epigenetic writers catalyzing the transfer of methyl-groups to cytosine-regulate stimulus-specific olfactory long-term memory (LTM) formation and extinction in honeybees. The physiological relevance of their function in neural networks, however, remains unknown. Here, we investigated how Dnmts impact neuroplasticity in the bees primary olfactory center, the antennal lobe (AL) an equivalent of the olfactory bulb of vertebrates. The AL is crucial for odor discrimination, an indispensable process in stimulus-specific LTM. Using pharmacological inhibition, we show that Dnmts promote fast odor pattern separation in trained bees. We show Dnmt activity during memory formation increases both the number of responding glomeruli and the response magnitude to a novel odor. These data suggest that Dnmts are necessary for a form of homoeostatic network control which might involve inhibitory interneurons in the AL network and demonstrate that Dnmts influence neural network properties during memory formation in vivo.

Neuroscience↗

bioRxiv2016

Proteobacteria drive significant functional variability in the human gut microbiome

While human gut microbiomes vary significantly in taxonomic composition, biological pathway abundance is surprisingly invariable across hosts. We hypothesized that healthy microbiomes appear functionally redundant due to factors that obscure differences in gene abundance across hosts. To account for these biases, we developed a powerful test of gene variability, applicable to shotgun metagenomes from any environment. Our analysis of healthy stool metagenomes reveals thousands of genes whose abundance differs signifi-cantly between people consistently across studies, including glycolytic enzymes, lipopolysac-charide biosynthetic genes, and secretion systems. Even housekeeping pathways contain a mix of variable and invariable genes, though most deeply conserved genes are significantly invariable. Variable genes tend to be associated with Proteobacteria, as opposed to taxa used to define enterotypes or the dominant phyla Bacteroidetes and Firmicutes. These re-sults establish limits on functional redundancy and predict specific genes and taxa that may drive physiological differences between gut microbiomes.\n\nImpact StatementA statistical test for gene variability reveals extensive functional differences between healthy humanmicrobiomes.

Bioinformatics↗

bioRxiv2016

The evolutionary basis of premature migration in Pacific salmon highlights the utility of genomics for informing conservation

The delineation of conservation units (CUs) is a challenging issue that has profound implications for minimizing the loss of biodiversity and ecosystem services. CU delineation typically seeks to prioritize evolutionary significance and genetic methods play a pivotal role in the delineation process by quantifying overall differentiation between populations. While CUs that primarily reflect overall genetic differentiation do protect adaptive differences between distant populations, they do not necessarily protect adaptive variation within highly connected populations. Advances in genomic methodology facilitate the characterization of adaptive genetic variation, but the potential utility of this information for CU delineation is unclear. Here we use genomic methods to investigate the evolutionary basis of premature migration in Pacific salmon, a complex behavioral and physiological adaptation that exists within highly-connected populations and has experienced severe declines. Strikingly, we find that premature migration is associated with the same single locus across multiple populations in each of two different species. Patterns of variation at this locus suggest that the premature migration alleles arose from a single evolutionary event within each species and were subsequently spread to distant populations through straying and positive selection. Our results reveal that complex adaptive variation can depend on rare mutational events at a single locus, demonstrate that CUs reflecting overall genetic differentiation can fail to protect evolutionarily significant variation that has substantial ecological and societal benefits, and suggest that a supplemental framework for protecting specific adaptive variation will sometimes be necessary to prevent the loss of significant biodiversity and ecosystem services.

Genetics↗

bioRxiv2016

KIF1A/UNC-104 transports ATG-9 to regulate neurodevelopment and autophagy at synapses

Autophagy is a cellular degradation process essential for neuronal development and survival. Neurons are highly polarized cells in which autophagosome biogenesis is spatially compartmentalized. The mechanisms and physiological importance of this spatial compartmentalization of autophagy in the neuronal development of living animals are not well understood. Here we determine that, in C. elegans neurons, autophagosomes form near synapses and are required for neurodevelopment. We first determined, through unbiased genetic screens and systematic genetic analyses, that autophagy is required cell-autonomously for presynaptic assembly and for axon outgrowth dynamics in specific neurons. We observe autophagosomes in the axon near synapses, and this localization depends on the synaptic vesicle kinesin, KIF1A/UNC-104. KIF1A/UNC-104 coordinates localized autophagosome formation by regulating the transport of the integral membrane autophagy protein, ATG-9. Our findings indicate that autophagy is spatially regulated in neurons through the transport of ATG-9 by KIF1A/UNC-104 to regulate neurodevelopment.

Cell Biology↗

bioRxiv2016

Geo-climatic gradient shapes functional trait variations in Salix eriocephala Michx.

Intraspecific variations in seasonal phenology and growth physiology reflect adaptation to local climate. To explore the patterns of local adaptation along latitudinal and longitudinal clines, we used thirty-four populations of Salix eriocephala sourced from its natural ranges across Canada. The genotypes were examined for 6 phenology and 19 ecophysiology traits over two growing seasons under common garden condition. Photosynthetic assimilation rate (A) increased with increasein latitude when measured during free growth. In spite, the negative correlation between stomatal density and stomatal conductance (gs), higher A is facilitated via larger pore length among genotypes from short growing seasons. In addition, higher A, was positively associated with total leafnitrogen and leaf mass per unit area. No population level differences wereobserved for water use-efficiency ({Delta}13C), however nitrogen isotope discrimination ({delta}15N) displayed latitudinalclines. Growing season phenological traits considered in this study accounted highheritability (H2=0.65-0.94). Melampsora rust infestation also displayed a strong latitudinal cline with high-latitude genotypes being more susceptible. Overall, the results support the hypothesis that functional trait variations are largely explained by climate of origin and facilitate selection of parents with superior adaptive traits in the Canadian willow improvement program forbioenergy and environmental applications.

Plant Biology↗

bioRxiv2016

Geo-climatic gradient shapes functional trait variations in Salix eriocephala Michx.

Intraspecific variations in seasonal phenology and growth physiology reflect adaptation to local climate. To explore the patterns of local adaptation along latitudinal and longitudinal clines, we used thirty-four populations of Salix eriocephala sourced from its natural ranges across Canada. The genotypes were examined for 6 phenology and 19 ecophysiology traits over two growing seasons under common garden condition. Photosynthetic assimilation rate (A) increased with increasein latitude when measured during free growth. In spite, the negative correlation between stomatal density and stomatal conductance (gs), higher A is facilitated via larger pore length among genotypes from short growing seasons. In addition, higher A, was positively associated with total leafnitrogen and leaf mass per unit area. No population level differences wereobserved for water use-efficiency ({Delta}13C), however nitrogen isotope discrimination ({delta}15N) displayed latitudinalclines. Growing season phenological traits considered in this study accounted highheritability (H2 = 0.65-0.94). Melampsora rust infestation also displayed a strong latitudinal cline with high-latitude genotypes being more susceptible. Overall, the results support the hypothesis that functional trait variations are largely explained by climate of origin and facilitate selection of parents with superior adaptive traits in the Canadian willow improvement program forbioenergy and environmental applications.

Plant Biology↗

bioRxiv2016

RiVIERA-MT: A Bayesian model to infer risk variants in related traits using summary statistics and functional genomic annotations

Dissecting the physiological circuitry underlying diverse human complex traits associated with heritable common mutations is an ongoing effort. The primary challenge involves identifying the relevant cell types and the causal variants among the vast majority of the associated mutations in the noncoding regions. To address this challenge, we developed an efficient probabilistic framework. First, we propose a sparse group-guided learning algorithm to infer cell-type-specific enrichments. Second, we propose a fine-mapping Bayesian model that incorporates as Bayesian priors the sparse enrichments to infer risk variants. Using the proposed framework to analyze 32 complex human traits revealed meaningful tissue-specific epigenomic enrichments indicative of the relevant disease pathologies. The prioritized variants exhibit prominent tissue-specific epigenomic signatures and significant enrichments for eQTL and conserved elements. Together, we demonstrate the general benefits of the proposed integrative framework in elucidating meaningful tissue-specific epigenomic elements from large-scale correlated annotations and the implicated functional variants for future experimental interrogation.

Bioinformatics↗

bioRxiv2016

Auditory Nerve Stochasticity Impedes Category Learning: the Role of Cochlear Nucleus and Inferior Colliculus in Stabilising Auditory Nerve Firing

It is well known that auditory nerve (AN) fibers overcome bandwidth limitations through the \"volley principle\", a form of multiplexing. What is less well known is that the volley principle introduces a degree of unpredictability into AN neural firing patterns which makes even simple stimulus categorization tasks difficult. We use a physiologically grounded, unsupervised spiking neural network model of the auditory brain with STDP learning to demonstrate that plastic auditory cortex is unable to learn even simple auditory object categories when exposed to the raw AN firing input without subcortical preprocessing. We then demonstrate the importance of non-plastic subcortical preprocessing within the cochlear nucleus (CN) and the inferior colliculus (IC) for stabilising and denoising AN responses. Such preprocessing enables the plastic auditory cortex to learn efficient robust representations of the auditory object categories. The biological realism of our model makes it suitable for generating neurophysiologically testable hypotheses.

Neuroscience↗

bioRxiv2016

Higher stress and immunity responses are associated with higher mortality in reef-building coral exposed to a bacterial challenge

Understanding the drivers of intraspecific variation in susceptibility is essential to manage increasingly frequent coral disease outbreaks. We challenged replicate fragments of eight Acropora millepora genotypes with Vibrio spp. to quantify variation in lesion development and to identify host and coral-associated microbial community properties associated with resistance. While Vibrio spp. remained relatively rare in the microbiome of challenged corals, other stress-associated microbial taxa significantly increased in abundance. Contrary to expectations, higher constitutive immunity and more active immune responses did not confer higher resistance to bacterial challenge. Furthermore, more pronounced gene expression responses to bacterial challenge were associated with higher rather than lower mortality. A newly developed gene expression assay based on two genes related to inflammation and immune responses, deleted in malignant brain tumors 1 and a matrix metalloproteinase, predicted mortality under Vibrio treatment both in the initial experiment and in a validation experiment involving another 20 A. millepora genotypes. Instead of mounting more robust responses, resistant corals were largely unaffected by the bacterial challenge and maintained gene expression signatures of healthier condition, including elevated fluorescent proteins and ribosomal biosynthesis along with diminished ubiquitination. Overall, our results support the view that coral disease and mortality is commonly due to opportunistic pathogens exploiting physiologically compromised hosts rather than specific infections, and show, contrary to the prevailing wisdom, that greater immune responses do not necessarily translate into greater disease resistance.

Ecology↗

bioRxiv2016

Unsupervised Learning of Temporal Features for Word Categorization in a Spiking Neural Network Model of the Auditory Brain

The nature of the code used in the auditory cortex to represent complex auditory stimuli, such as naturally spoken words, remains a matter of debate. Here we argue that such representations are encoded by stable spatio-temporal patterns of firing within cell assemblies known as polychronous groups, or PGs. We develop a physiologically grounded, unsupervised spiking neural network model of the auditory brain with local, biologically realistic, spike-time dependent plasticity (STDP) learning, and show that the plastic cortical layers of the network develop PGs which convey substantially more information about the speaker independent identity of two naturally spoken word stimuli than does rate encoding that ignores the precise spike timings. We furthermore demonstrate that such informative PGs can only develop if the input spatio-temporal spike patterns to the plastic cortical areas of the model are relatively stable.\n\nAuthor SummaryCurrently we still do not know how the auditory cortex encodes the identity of complex auditory objects, such as words, given the great variability in the raw auditory waves that correspond to the different pronunciations of the same word by different speakers. Here we argue for temporal information encoding within neural cell assemblies for representing auditory objects. Unlike the more traditionally accepted rate encoding, temporal encoding takes into account the precise relative timing of spikes across a population of neurons. We provide support for our hypothesis by building a neurophysiologically grounded spiking neural network model of the auditory brain with a biologically plausible learning mechanism. We show that the model learns to differentiate between naturally spoken digits \"one\" and \"two\" pronounced by numerous speakers in a speaker-independent manner through simple unsupervised exposure to the words. Our simulations demonstrate that temporal encoding contains significantly more information about the two words than rate encoding. We also show that such learning depends on the presence of stable patterns of firing in the input to the cortical areas of the model that are performing the learning.

Neuroscience↗

bioRxiv2016

Temperature-induced transcriptional responses of the deep-biosphere bacterium, Kosmotoga olearia, illuminate its adaptation to growth from 20 ° to 79°

Temperature is one of the defining parameters of an ecological niche. Most organisms thrive within a temperature range that rarely exceeds [~] 30{degrees}C, but the deep subsurface bacterium Kosmotoga olearia can grow over a temperature range of 59{degrees}C (20{degrees}C -79{degrees}C). To identify genes correlated with this flexible phenotype, we compared transcriptomes of K. olearia cultures grown at its optimal 65{degrees}C to those at 30{degrees}C, 40{degrees}C, and 77{degrees}C. The temperature treatments affected expression of 573 of 2,224 K. olearia genes. Notably, this transcriptional response elicits re-modeling of the cellular membrane and changes in metabolism, with increased expression of genes involved in energy and carbohydrate metabolism at high temperatures and up-regulation of amino acid metabolism at lower temperatures. At sub-optimal temperatures, many transcriptional changes were similar to those observed in mesophilic bacteria at physiologically low temperatures, including up-regulation of typical cold stress genes and ribosomal proteins. Comparative genomic analysis of additional Thermotogae genomes, indicate that one of K. olearia's strategies for low temperature growth is increased copy number of some typical cold response genes through duplication and/or lateral acquisition. At 77{degrees}C one third of the up-regulated genes are of hypothetical function, indicating that many features of high temperature growth are unknown.

Evolutionary Biology↗

bioRxiv2016

Evolutionary genomics of peach and almond domestication

The domesticated almond [Prunus dulcis (L.) Batsch] and peach [P. persica (Mill.) D. A. Webb] originate on opposite sides of Asia and were independently domesticated approximately 5000 years ago. While interfertile, they possess alternate mating systems and differ in a number of morpholog-ical and physiological traits. Here we evaluated patterns of genome-wide diversity in both almond and peach to better understand the impacts of mating system, adaptation, and domestication on the evolution of these taxa. Almond has [~]7X the genetic diversity of peach, and high genome-wide FST values support their status as separate species. We estimated a divergence time of approximately 8 Mya, coinciding with an active period of uplift in the northeast Tibetan Plateau and subsequent Asian climate change. We see no evidence of bottleneck during domestication of either species, but identify a number of regions showing signatures of selection during domestication and a significant overlap in candidate regions between peach and almond. While we expected gene expression in fruit to overlap with candidate selected regions, instead we find enrichment for loci highly differentiated between the species, consistent with recent fossil evidence suggesting fruit divergence long preceded domestication. Taken together this study tells us how closely related tree species evolve and are domesticated, the impact of these events on their genomes, and the utility of genomic information for long-lived species. Further exploration of this data will contribute to the genetic knowledge of these species and provide information regarding targets of selection for breeding application and further the understanding of evolution in these species.

Evolutionary Biology↗

bioRxiv2016

Optimization of an anti Staphylococcus antibiotic produced by tropical soil dwelling Streptomyces parvulus

An antibiotic produced by strain Streptomyces parvulus showing activity against Staphylococcus citreus was subjected to various optimization parameters for enhancing its production. Nutritional and physiological parameters produced by S. parvulus under shaken flask conditions were determined. Optimization of these parameters led to 11% increase in antibiotic activity with a mean zone of inhibition of 42 mm.\n\nHighest antibiotic production was obtained at 250 rpm for 14 days with optimum temperature of 28{degrees}C and pH 7. Kuster#x2019;s modified medium containing glycerol 0.7% (v/v), casein 0.03% (w/v), NaCl 0% (w/v), phosphate 0.25% (w/v), KNO3 0.1% (w/v) and CaCO3 0.0015% (w/v) concentration was found ideal.

Microbiology↗

bioRxiv2016

Disorder Atlas: a web service for the proteome-based interpretation of intrinsic disorder predictions

BackgroundIntrinsically disordered proteins lack a stable three-dimensional structure under physiological conditions. While this property has gained considerable interest within the past two decades, disorder poses substantial challenges to experimental characterization efforts. In effect, numerous computational tools have been developed to predict disorder from primary sequences, however, interpreting the output of these algorithms remains a challenge.\n\nResultsHere, we present Disorder Atlas, web-based software that facilitates the interpretation of intrinsic disorder predictions using proteome-based descriptive statistics. This service is also equipped to facilitate large-scale systematic exploratory searches for proteins encompassing disorder features of interest, and further allows users to browse the prevalence of multiple disorder features at the proteome level. Disorder Atlas is freely available for non-commercial users at http://www.disorderatlas.org.\n\nConclusionDisorder Atlas enables a standardized interpretation of intrinsic disorder predictions, and provides researchers with a tool to assess disorder on multiple scales.

Bioinformatics↗

bioRxiv2016

Decoding the Infant Mind: Multichannel Pattern Analysis (MCPA) using fNIRS

The MRI environment restricts the types of populations and tasks that can be studied by cognitive neuroscientists (e.g., young infants, face-to-face communication). FNIRS is a neuroimaging modality that records the same physiological signal as fMRI but without the constraints of MRI, and with better spatial localization than EEG. However, research in the fNIRS community largely lacks the analytic sophistication of analogous fMRI work, restricting the application of this imaging technology. The current paper presents a method of multivariate pattern analysis for fNIRS that allows the authors to decode the infant mind (a key fNIRS population). Specifically, multi-channel pattern analysis (MCPA) employs a correlation-based decoding method where a group model is constructed for all infants except one; both average patterns (i.e., infant-level) and single trial patterns (i.e., trial-level) of activation are decoded. Between subjects decoding is a particularly difficult task, because each infant has their own somewhat idiosyncratic patterns of neural activation. The fact that our method succeeds at across-subject decoding demonstrates the presence of group-level multi-channel regularities across infants. The code for implementing these analyses has been made readily available online to facilitate the quick adoption of this method to advance the methodological tools available to the fNIRS researcher.

Neuroscience↗