SEARCH · Search bioRxiv

Results for “Genetics”

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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,387 records · Page 77Linked to original sources

bioRxiv2016

Ploidy tug-of-war: evolutionary and genetic environments influence the rate of ploidy drive in a human fungal pathogen

Variation in baseline ploidy is seen throughout the tree of life, yet the factors that determine why one ploidy level is selected over another remain poorly understood. Experimental evolution studies using asexual fungal microbes with manipulated ploidy levels intriguingly reveals a propensity to return to the historical baseline ploidy, a phenomenon that we term ploidy drive. We evolved haploid, diploid, and polyploid strains of the human fungal pathogen Candida albicans under three different nutrient limitation environments to test whether these conditions, hypothesized to select for low ploidy levels, could counteract ploidy drive. Strains generally maintained or acquired smaller genome sizes in minimal medium and under phosphorus depletion compared to in a complete medium, while mostly maintained or acquired increased genome sizes under nitrogen depletion. Surprisingly, improvements in fitness often ran counter to changes in total nuclear genome size; in a number of scenarios lines that maintained their original genome size often increased in fitness more than lines that converged towards diploidy. Combined, this work demonstrates a role for both the environment and genotype in determination of the rate of ploidy drive, and highlights questions that remain about the force(s) that cause genome size variation.

evolutionary biology↗

bioRxiv2016

Genetic variation for mitochondrial function in the New Zealand freshwater snail Potamopyrgus antipodarum

The proteins responsible for mitochondrial function are encoded by two different genomes with distinct inheritance regimes, rendering rigorous inference of genotype-phenotype connections intractable for all but a few model systems. Asexual organisms provide a powerful means for addressing these challenges because offspring produced without recombination inherit both nuclear and mitochondrial genomes from a single parent. As such, these offspring inherit mitonuclear genotypes that are identical to the mitonuclear genotypes of their parents and siblings and different from those of other asexual lineages. Here, we compared mitochondrial function across distinct asexual lineages of Potamopyrgus antipodarum, a New Zealand freshwater snail model for understanding the evolutionary consequences of asexuality. Our analyses revealed substantial phenotypic variation across asexual lineages at three levels of biological organization: mitogenomic, organellar, and organismal. These data demonstrate that different asexual lineages have different mitochondrial function phenotypes and that there exists heritable variation (that is, the raw material for evolution) for mitochondrial function in P. antipodarum. The discovery of this variation combined with the methods developed here sets the stage to use P. antipodarum to study central evolutionary questions involving mitochondrial function, including whether mitochondrial mutation accumulation influences the maintenance of sexual reproduction in natural populations.

evolutionary biology↗

bioRxiv2016

Temporal Genetic Dynamics of an Experimental, Biparental Field Population of Phytophthora capsici

Defining the contributions of dispersal, reproductive mode, and mating system to the population structure of a pathogenic organism is essential to estimating its evolutionary potential. After introduction of the devastating plant pathogen, Phytophthora capsici, into a growers field, a lack of aerial spore dispersal restricts migration. Once established, coexistence of both mating types results in formation of overwintering recombinant oospores, engendering persistent pathogen populations. To mimic these conditions, in 2008, we inoculated a field with two P. capsici isolates of opposite mating type. We analyzed pathogenic isolates collected in 2009-13 from this experimental population, using genome-wide single-nucleotide polymorphism markers. By tracking heterozygosity across years, we show that the population underwent a generational shift; transitioning from exclusively F1 in 2009-10; mixed generational in 2011; and ultimately all inbred in 2012-13. Survival of F1 oospores, characterized by heterozygosity excess, coupled with a low rate of selfing, delayed declines in heterozygosity due to inbreeding and attainment of equilibrium genotypic frequencies. Large allele and haplotype frequency changes in specific genomic regions accompanied the generational shift, representing putative signatures of selection. Finally, we identified an approximately 1.6 Mb region associated with mating type determination, constituting the first detailed genomic analysis of a mating type region (MTR) in Phytophthora. Segregation patterns in the MTR exhibited tropes of sex-linkage, where maintenance of allele frequency differences between isolates of opposite mating type was associated with elevated heterozygosity despite inbreeding. Characterizing the trajectory of this experimental system provides key insights into the processes driving persistent, sexual pathogen populations.

evolutionary biology↗

bioRxiv2017

Density-dependent selection in evolutionary genetics: a lottery model of Grime’s triangle

Selection is commonly described by assigning constant relative fitness values to genotypes. Yet population density is often regulated by crowding. Relative fitness may then depend on density, and selection can change density when it acts on a density-regulating trait. When strong density-dependent selection acts on a density-regulating trait, selection is no longer describable by density-independent relative fitnesses, even in demographically stable populations. These conditions are met in most previous models of density-dependent selection (e.g. \"K-selection\" in the logistic and Lotka-Volterra models), suggesting that density-independent relative fitnesses must be replaced with more ecologically explicit absolute fit-nesses unless selection is weak. Here we show that density-independent relative fitnesses can also accurately describe strong density-dependent selection under some conditions. We develop a novel model of density-regulated population growth with three ecologically intuitive traits: fecundity, mortality, and competitive ability. Our model, unlike the logistic or Lotka-Volterra, incorporates a density-dependent juvenile \"reproductive excess\", which largely decouples density-dependent selection from the regulation of density. We find that density-independent relative fitnesses accurately describe strong selection acting on any one trait, even fecundity, which is both density-regulating and subject to density-dependent selection. Pleiotropic interactions between these traits recovers the familiar K-selection behavior. In such cases, or when the population is maintained far from demographic equilibrium, our model offers a possible alternative to relative fitness.

evolutionary biology↗

bioRxiv2017

WIDE-SCALE COMPARATIVE ANALYSIS OF LONGEVITY GENES AND GENETIC INTERVENTIONS

Hundreds of genes have been identified as being involved in the control of lifespan in the four common model organisms (yeast, worm, fruit fly and mouse). A major challenge is to determine if longevity-associated genes (LAGs) are model-specific or may play a universal role as longevity regulators across diverse taxa. A wide-scale comparative analysis of the 1,805 known LAGs across 205 species revealed that (i) LAG orthologs are substantially over-represented, from bacteria to mammals, especially noted for essential LAGs; (ii) the effects on lifespan, when manipulating orthologous LAGs in different model organisms, were mostly concordant, despite of a high evolutionary distance between them; (iii) the most conserved LAGs were enriched in translational processes, energy metabolism, development, and DNA repair. The least conserved LAGs were enriched in autophagy (Fungi), G-proteins (Nematodes), and neuroactive ligand-receptor interactions (Chordata). The results also suggest that antagonistic pleiotropy is a conserved principle of aging.

systems biology↗

bioRxiv2017

Clay-induced DNA double-strand breaks underlay genetic diversity, antibiotic resistance and molecular basis of asbestosis

Some natural clays and synthetic nanofibres present in the environment have a severe impact on human health. After several decades of research, the molecular mechanism of how asbestos induce cancers is not well understood. Different fibres, including asbestos, can penetrate the membrane and introduce DNA in both, bacterial and eukaryotic cells. Incubating Escherichia coli with sepiolite, a clayey material, and asbestos under friction forces, both fibres cause double-strand breaks in bacteria. Since antibiotics and clays are used together in animal husbandry, the mutagenic effect of these fibres might constitute a pathway to antibiotic resistance due to the friction provided by peristalsis of the gut from farm animals in addition to the previously proposed horizontal gene transfer. Moreover, we raise the possibility that the same mechanism could generate bacteria diversity in natural scenarios with a role in the evolution of species. Finally, we provide a new model on how asbestos may promote mutagenesis and cancer based on the observed mechanical genotoxicity.

evolutionary biology↗

bioRxiv2017

Genetic characterization of the Zika virus epidemic in the US Virgin Islands

Here we release draft genome sequences of Zika virus (ZIKV) that were sequenced from PCR-positive diagnostic specimens collected by the United States Virgin Islands Department of Health (USVI DoH) as part of their ongoing response to the ZIKV outbreak. We will use these sequences to conduct a genomic epidemiological study of ZIKV transmission in the USVI. We are releasing these genomes in the hope that they are useful for those individuals involved in the public health response to ZIKV and to other groups working to understand Zika virus transmission and evolution.

epidemiology↗

bioRxiv2017

A Comprehensive Assessment of the Genetic Determinants in Salmonella Typhimurium for Resistance to Hydrogen Peroxide

Salmonella is an intracellular pathogen that infects a wide range of hosts and can survive in macrophages. An essential mechanism uses by the macrophages to eradicate Salmonella is production of reactive oxygen species. Here, we used proteogenomics to determine the candidate genes and proteins that have a role in resistance of S. Typhimurium to H2O2. For Tn-seq, a highly saturated Tn5 insertion library was grown in vitro under either 2.5 (H2O2L) or 3.5 mM H2O2 (H2O2H). We identified two sets of overlapping genes that are required for resistance of S. Typhimurium to H2O2L and H2O2H, and the results were validated via phenotypic evaluation of 50 selected mutants. The enriched pathways for resistance to H2O2 included DNA repair, aromatic amino acid biosynthesis (aroBK), Fe-S cluster biosynthesis, iron homeostasis and a putative iron transporter system (ybbKLM), flagellar genes (fliBC), H2O2 scavenging enzymes, and DNA adenine methylase. Proteomics revealed that the majority of essential proteins, including ribosomal proteins, were downregulated upon exposure to H2O2. A subset of proteins identified by Tn-seq were analyzed by targeted proteomics, and 70% of them were upregulated upon exposure to H2O2. The identified candidate genes will deepen our understanding about mechanisms of S. Typhimurium survival in macrophages, and can be exploited to develop new antimicrobial drugs.

microbiology↗

bioRxiv2017

The Maternal Environment Interacts With Genetic Variation In Regulating Seed Dormancy In Arabidopsis thaliana

Seed dormancy is a complex adaptive trait that controls the timing of seed germination, one of the major fitness components in many plant species. Despite being highly heritable, seed dormancy is extremely plastic and influenced by a wide range of environmental cues. Here, using a set of 92 Arabidopsis thaliana lines from Sweden, we investigate the effect of seed maturation temperature on dormancy variation at the population level. The response to temperature differs dramatically between lines, demonstrating that genotype and the maternal environment interact in controlling the trait. By performing a genome-wide association study (GWAS), we identified several candidate genes that could account for this plasticity, two of which are involved in the photoinduction of germination. Altogether, our results provide insight into both the molecular mechanisms and the evolution of dormancy plasticity, and can serve to improve our understanding of environmentally dependent life-history transitions.\n\nHighlightThe effect of low seed-maturation temperatures on seed dormancy is highly variable in Arabidopsis thaliana accessions from Sweden, denoting strong genotype-environment interactions, and a genome-wide association study identified compelling candidates that could account for this plasticity.

plant biology↗

bioRxiv2017

The Cellular Expression and Genetics of an Established Polymorphism in Poecilia reticulata; Purple Body, (Pb) is an Autosomal Dominant Gene

Modification of wild-type carotenoid orange and pteridine red coloration and spotting of male ornaments in both wild populations of Poecilia reticulata (Guppies) and modern Domestic Guppy strains by the Purple Body gene has long been overlooked in research articles and little understood in breeder publications. This modification is commonly found in wild-type Poecilia reticulata reticulata populations from numerous collection sites and has been photographed but not recognized in these collections. It is non-existent or near absent in collections taken from variant populations of Poecilia reticulata wingei. We identify and determine the mode of inheritance, cellular and phenotypic expression by the Purple gene in these stocks. The Purple Body color pigment modification is a distinct polymorphism in wild P. reticulata reticulata populations. Its existence suggests multiple benefits that satisfy female sexual selection preferences, and minimize or reduce potential predation risks. Photographic and microscopic evidence demonstrated that Purple Body is a normal polymorphism in wild and domestic guppies modifying color pigment regions. Purple Body is inherited as an autosomal incompletely dominant trait.

evolutionary biology↗

bioRxiv2017

The Cellular Expression and Genetics of Purple Body (Pb) in Poecilia reticulata, and its Interactions with Asian Blau (Ab) and Blond (bb) under Reflected and Transmitted Light

Mature Purple Body and Non-Purple Body male guppies differ from each other in several ways. Non-Purple males may have large numbers of xanthophores, erythrophores, and blue iridophores, in addition to the usual dendritic, corolla and punctate melanophores. Fewer violet iridophores are found. In contrast, homozygous Purple Body males lack collected and clustered xanthophores, although isolated single xanthophores remain. Violet iridophores and blue iridophores (violet-blue chromatophores units) abound. The dendrites of dendritic melanophores are finer and form chains with each other. Punctate and corolla melanophores in areas comprising orange ornaments are greatly reduced in number. The heterozygous Purple Body male has erythrophores similar to those of non-Purple males, but yellow pigment is reduced. The melanophores are not as greatly changed in orange ornaments. In Domestic Guppy strains, and at least in one suspected instance in wild-type, melanophore structure and populations may be further modified by one or more additional autosomal genes.

evolutionary biology↗

bioRxiv2017

The Cellular Expression and Genetics of Purple Body (Pb) in the Ocular Media of the Guppy Poecilia reticulata

Our study revealed the presence of all major classes of chromatophores (melanophores, xanthophores, erythrophores, violet-blue iridophores, xantho-erythrophores) and crystalline platelets in various combinations in the iris and ocular media (cornea, aqueous humor, vitreous humor, outer lens membrane) of Poecilia reticulata. This novel ocular media study of P. reticulata takes into account the distinct interactions of Purple Body (Pb) based on results of previous Bias and Squire Purple Body (Pb) publications. Taken in conjunction with other researchers published results (regarding UV reflected color and pattern, vision, mate choice, individual preferences, and opsin capabilities) this indicates that these ocular chromatophore populations together create a complex ocular filter mechanism. This mechanism in turn provides spectral capabilities into the UV and Near-UV wavelengths in both Pb and non-Pb individuals. The chromatophores in the cornea, aqueous humor, covering membranes of the lens, and the vitreous humor comprise an ocular filter system that could reduce UV damage to the internal structures of the eye. The guppys ability to use UVA as a visual component provides a \"private signally system\" that cannot be detected by some predators. While non-Pb guppies should derive benefit in the near-UV from violet-blue iridophore units, greater benefit will be derived by Pb individuals with more violet iridophores functioning in the lower UV and near-UV wavelengths. To our knowledge little has been published for P. reticulata concerning pigmentation within the guppy eye. Macroscopic and microscopic imagery is presented.

evolutionary biology↗

bioRxiv2017

The WPRE Improves Genetic Engineering With Site-Specific Nucleases

AbstractInclusion of the woodchuck hepatitis virus post-transcriptional response element (WPRE) in the 3 UTR of mRNA encoding zinc-finger or TALE nucleases results in up to a fifty-fold increase in nuclease expression and a several-fold increase in nuclease-modified chromosomes. Significantly, this increase is additive with the enhancement generated by transient hypothermic shock. The WPRE-mediated improvement is seen across several types of human and mouse primary and transformed cells and is translatable in vivo to the mouse liver.

synthetic biology↗

bioRxiv2017

Systematic Genetic Dissection Of Chitin Degradation And Uptake In Vibrio cholerae

Vibrio cholerae is a natural resident of the aquatic environment, where a common nutrient is the chitinous exoskeletons of microscopic crustaceans. Chitin utilization requires chitinases, which degrade this insoluble polymer into soluble chitin oligosaccharides. These oligosaccharides also serve as an inducing cue for natural transformation in Vibrio species. There are 7 predicted endochitinase-like genes in the V. cholerae genome. Here, we systematically dissect the contribution of each gene to growth on chitin as well as induction of natural transformation. Specifically, we created a strain that lacks all 7 putative chitinases and from this strain, generated a panel of strains where each expresses a single chitinase. We also generated expression plasmids to ectopically express all 7 chitinases in our chitinase deficient strain. Through this analysis, we found that low levels of chitinase activity are sufficient for natural transformation, while growth on insoluble chitin as a sole carbon source requires more robust and concerted chitinase activity. We also assessed the role that the three uptake systems for the chitin degradation products GlcNAc, (GlcNAc)2, and (GlcN)2, play in chitin utilization and competence induction. Cumulatively, this study provides mechanistic details for how this pathogen utilizes chitin to thrive and evolve in its environmental reservoir.\n\nORIGINALITY-SIGNIFICANCE STATEMENTVibrio cholerae, the causative agent of the diarrheal disease cholera, interacts with the chitinous shells of crustacean zooplankton in the aquatic environment, which serves as an environmental reservoir for this pathogen. It degrades and utilizes chitin-derived products as a source of carbon and nitrogen. Also, chitin serves as an inducing cue for natural transformation - an important mechanism of horizontal gene transfer in this species. Here, we systematically dissect the genes required for chitin degradation and uptake, and characterize the role of these genes for growth on chitin as a nutrient and during chitininduced natural transformation. Thus, this study provides mechanistic details for how this pathogen utilizes chitin to thrive and evolve in its environmental reservoir.

microbiology↗

bioRxiv2017

A Core Speech Circuit Between Primary Motor, Somatosensory, And Auditory Cortex: Evidence From Connectivity And Genetic Descriptions

What adaptations allow humans to produce and perceive speech so effortlessly? We show that speech is supported by a largely undocumented core of structural and functional connectivity between the central sulcus (CS or primary motor and somatosensory cortex) and the transverse temporal gyrus (TTG or primary auditory cortex). Anatomically, we show that CS and TTG cortical thickness covary across individuals and that they are connected by white matter tracts. Neuroimaging network analyses confirm the functional relevance and specificity of these structural relationships. Specifically, the CS and TTG are functionally connected at rest, during natural audiovisual speech perception, and are coactive over a large variety of linguistic stimuli and tasks. Importantly, across structural and functional analyses, connectivity of regions immediately adjacent to the TTG are with premotor and prefrontal regions rather than the CS. Finally, we show that this structural/functional CS-TTG relationship is mediated by a constellation of genes associated with vocal learning and disorders of efference copy. We propose that this core circuit constitutes an interface for rapidly exchanging articulatory and acoustic information and discuss implications for current models of speech.

neuroscience↗

bioRxiv2017

Brain xQTL Map: Integrating The Genetic Architecture Of The Human Brain Transcriptome And Epigenome

We perform quantitative trait locus (xQTL) analyses on a multi-omic dataset, comprising RNA sequence, DNA methylation, and histone acetylation ChIP sequence data from the dorsolateral prefrontal cortex of 411 older adult individuals. We identify SNPs that are significantly associated with gene expression, DNA methylation, and histone modification levels. Many SNPs influence more than one type of molecular feature, and epigenetic features are shown to mediate eQTLs in a number of (9%) such loci. We illustrate the utility of our new resource, xQTL Serve, in prioritizing the cell type most affected by an xQTL and in enhancing genome wide association studies (GWAS) as we report 18 additional CNS disease susceptibility loci after re-analyzing published studies.

bioinformatics↗

bioRxiv2017

Pathogen Dependent Phenotypic But No Genetic Correlation Between Sexual Activity And Immunity In Male Drosophila melanogaster Subjected To Differential Sexual Selection

The theory of trade-off suggest that limited resources should lead to trade-off in resource intensive traits such as immunity related and sexually selected traits in males. Alternatively, sexual exaggerations can also act as an honest indicator of underlying immunocompetence, leading to positive correlations between these traits. Several studies have addressed this question using experimental evolution. However, they have rarely used ecologically relevant pathogens and fitness measurement (e.g., measuring post-infection survivorship) to find correlations between sexual selection and immunity. Here we attempt to address this caveat by evolving populations of Drosophila melanogaster under differential sexual selection. After more than hundred generations, we infected virgin and mated males from each population with three pathogenic bacteria: Pseudomonas entomophila (Pe), Staphylococcus succinus (Ss) and Providentia rettgeri (Pr). Fitness was measured as either post-infection survivorship (Pe and Ss) or bacterial clearance ability (Pr). Contrary to expectations, sexual selection had no evolutionary effect on male fitness against any of the pathogens. Moreover, mating had a beneficial effect against Pe and Pr, but no effect against Ss, suggesting pathogen specific phenotypic correlations between mating and immunity. Following these results, we discuss the significance of using ecologically relevant pathogens and quantifying host fitness while studying sexual selection-immunity correlations.

evolutionary biology↗

bioRxiv2017

Genetically modified human type II collagen for N- and C-terminal covalent tagging

Collagen is the predominant structural protein in vertebrates, where it contributes to connective tissues and the extracellular matrix; it is also widely used in biomaterials and tissue engineering. Dysfunction of this protein and its processing can lead to a wide variety of developmental disorders and connective tissue diseases. Recombinantly engineering the protein is challenging due to posttranslational modifications generally required for its stability and secretion from cells. Introducing end labels into the protein is problematic, because the N- and C-termini of the physiologically relevant tropocollagen lie internal to the initially flanking N- and C-propeptide sequences. Here, we introduce mutations into human type II procollagen in a manner that address these concerns, and purify the recombinant protein from a stably transfected HT1080 human fibrosarcoma cell line. Our approach introduces chemically addressable groups into the N- and Ctelopeptide termini of tropocollagen. Simultaneous overexpression of formylglycine generating enzyme (FGE) allows the endogenous production of an aldehyde tag in a defined, substituted sequence in the N-terminus of the mutated collagen, while the C-terminus of each chain presents a sulfhydryl group from an introduced cysteine. These modifications are designed to enable specific covalent end-labelling of collagen. We find that the doubly-mutated protein folds and is secreted from cells, while higher-order assembly into well-ordered collagen fibrils is demonstrated through transmission electron microscopy. Chemical tagging of thiols is successful, however background from endogenous aldehydes present in wildtype collagen has thus far obscured the desired specific N-terminal labelling. Strategies to overcome this challenge are proposed.

biochemistry↗