Metabonomic, transcriptomic, and genomic variation of a population cohort.
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ABSTRACT:
SUBMITTER: Inouye M
PROVIDER: S-EPMC3018170 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Whole-genome sequence data from samples of natural populations provide fertile grounds for analyses of intraspecific variation and tests of population genetic theory. We show that the urochordate Ciona savignyi, one of the species of ocean-dwelling broadcast spawners commonly known as sea squirts, exhibits the highest rates of single-nucleotide and structural polymorphism ever comprehensively quantified in a multicellular organism. We demonstrate that the cause for the extreme heterozygosity is a large effective population size, and, consistent with prediction by the neutral theory, we find evidence of strong purifying selection. These results constitute in-depth insight into the dynamics of highly polymorphic genomes and provide important empirical support of population genetic theory as it pertains to population size, heterozygosity, and natural selection.
| S-EPMC1838466 | biostudies-literature
Project description:BackgroundThe emergence of macrolide resistance in Bordetella pertussis, the causative agent of pertussis, due to mutations in the 23S rRNA gene has been recently recognized. However, resistance mechanisms to macrolides in Bordetella parapertussis and Bordetella holmesii remain unknown.ObjectivesThis study investigated genomic changes induced by in vitro exposure to erythromycin in these three main pathogens responsible for pertussis-like disease.MethodsA set of 10 clinical and reference strains of B. pertussis, B. parapertussis and B. holmesii was exposed to erythromycin for 15 weeks or 30 subculture passages. Antibiotic pressure was achieved by growth on the selective media with erythromycin Etest strips or impregnated discs. Genome polymorphisms and transcriptomic profiles were examined by short- and long-read sequencing of passaged isolates.ResultsB. parapertussis and B. holmesii isolates developed significant in vitro resistance to erythromycin (MIC >256 mg/L) within 2 to 7 weeks and at 5 to 12 weeks, respectively. B. pertussis remained phenotypically susceptible to the antibiotic following 15 weeks of exposure, with the MIC between 0.032 to 0.38 mg/L. Genomic analysis revealed that B. holmesii developed resistance due to mutations in the 23S rRNA gene. The resistance mechanism in B. parapertussis was hypothesized as being due to upregulation of an efflux pump mechanism.ConclusionsThese findings indicate that both B. holmesii and B. parapertussis can be more prone to induced resistance following exposure to treatment with erythromycin than B. pertussis. The surveillance of macrolide resistance in Bordetella isolates recovered from patients with pertussis, especially persistent disease, is warranted.
| S-EPMC9616548 | biostudies-literature
Project description:Hybridization can lead to phenotypic differences arising from changes in gene expression patterns or new allele combinations. Variation in gene expression is thought to be controlled by differences in transcription regulation of parental alleles, either through cis- or trans-regulatory elements. A previous study among brook charr hybrids from different populations (Rupert, Laval, and domestic) showing distinct length at age during early life stages also revealed different patterns in transcription regulation inheritance of transcript abundance. In the present study, transcript abundance using RNA-sequencing and quantitative real-time PCR, single-nucleotide polymorphism (SNP) genotypes and allelic imbalance were assessed in order to understand the molecular mechanisms underlying the observed transcriptomic and differences in length at age among domestic × Rupert hybrids and Laval × domestic hybrids. We found 198 differentially expressed genes between the two hybrid crosses, and allelic imbalance could be analyzed for 69 of them. Among these 69 genes, 36 genes exhibited cis-acting regulatory effects in both of the two crosses, thus confirming the prevalent role of cis-acting regulatory elements in the regulation of differentially expressed genes among intraspecific hybrids. In addition, we detected a significant association between SNP genotypes of three genes and length at age. Our study is thus one of the few that have highlighted some of the molecular mechanisms potentially involved in the differential phenotypic expression in intraspecific hybrids for nonmodel species.
| S-EPMC3630814 | biostudies-literature
Project description:Gene duplication is a major driver of organismal evolution. Gene retroposition is a mechanism of gene duplication whereby a gene's transcript is used as a template to generate retroposed gene copies, or retrocopies. Intriguingly, the formation of retrocopies depends upon the enzymatic machinery encoded by retrotransposable elements, genomic parasites occurring in the majority of eukaryotes. Most retrocopies are depleted of the regulatory regions found upstream of their parental genes; therefore, they were initially considered transcriptionally incompetent gene copies, or retropseudogenes. However, examples of functional retrocopies, or retrogenes, have accumulated since the 1980s. Here, we review what we have learned about retrocopies in animals, plants and other eukaryotic organisms, with a particular emphasis on comparative and population genomic analyses complemented with transcriptomic datasets. In addition, these data have provided information about the dynamics of the different "life cycle" stages of retrocopies (i.e., polymorphic retrocopy number variants, fixed retropseudogenes and retrogenes) and have provided key insights into the retroduplication mechanisms, the patterns and evolutionary forces at work during the fixation process and the biological function of retrogenes. Functional genomic and transcriptomic data have also revealed that many retropseudogenes are transcriptionally active and a biological role has been experimentally determined for many. Finally, we have learned that not only non-long terminal repeat retroelements but also long terminal repeat retroelements play a role in the emergence of retrocopies across eukaryotes. This body of work has shown that mRNA-mediated duplication represents a widespread phenomenon that produces an array of new genes that contribute to organismal diversity and adaptation.
| S-EPMC5470649 | biostudies-other
Project description:Watermelon (Citrullus lanatus) is one of the most popular fruit crops. However, Fusarium wilt (FW) is a serious soil-borne disease caused by Fusarium oxysporum f. sp. niveum (FON) that severely limits the development of the watermelon industry. Trichoderma spp. is an important plant anti-pathogen biocontrol agent. The results of our previous study indicated that Trichoderma asperellum M45a (T. asperellum M45a) could control FW by enhancing the relative abundance of plant growth-promoting rhizobacteria (PGPR) in the rhizosphere of watermelon. However, there are few studies on its mechanism in the pathogen resistance of watermelon. Therefore, transcriptome sequencing of T. asperellum M45a-treated watermelon roots combined with metabolome sequencing of the rhizosphere soil was performed with greenhouse pot experiments. The results demonstrated that T. asperellum M45a could stably colonize roots and significantly increase the resistance-related enzymatic activities (e.g., lignin, cinnamic acid, peroxidase and peroxidase) of watermelon. Moreover, the expression of defense-related genes such as MYB and PAL in watermelon roots significantly improved with the inoculation of T. asperellum M45a. In addition, KEGG pathway analysis showed that a large number of differentially expressed genes were significantly enriched in phenylpropane metabolic pathways, which may be related to lignin and cinnamic acid synthesis, thus further inducing the immune response to resist FON. Furthermore, metabolic analysis indicated that four differential metabolic pathways were enriched in M45a-treated soil, including six upregulated compounds and one down-regulated compound. Among them, galactinol and urea were significantly positively correlated with Trichoderma. Hence, this study provides insight into the biocontrol mechanism of T. asperellum M45a to resist soil-borne diseases, which can guide its industrial application.
| S-EPMC9365129 | biostudies-literature
Project description:Cryptococcus neoformans is the causative agent of cryptococcosis, a disease with poor patient outcomes that accounts for approximately 180,000 deaths each year. Patient outcomes may be impacted by the underlying genetics of the infecting isolate; however, our current understanding of how genetic diversity contributes to clinical outcomes is limited. Here, we leverage clinical, in vitro growth and genomic data for 284 C. neoformans isolates to identify clinically relevant pathogen variants within a population of clinical isolates from patients with human immunodeficiency virus (HIV)-associated cryptococcosis in Malawi. Through a genome-wide association study (GWAS) approach, we identify variants associated with the fungal burden and the growth rate. We also find both small and large-scale variation, including aneuploidy, associated with alternate growth phenotypes, which may impact the course of infection. Genes impacted by these variants are involved in transcriptional regulation, signal transduction, glycosylation, sugar transport, and glycolysis. We show that growth within the central nervous system (CNS) is reliant upon glycolysis in an animal model and likely impacts patient mortality, as the CNS yeast burden likely modulates patient outcome. Additionally, we find that genes with roles in sugar transport are enriched in regions under selection in specific lineages of this clinical population. Further, we demonstrate that genomic variants in two genes identified by GWAS impact virulence in animal models. Our approach identifies links between the genetic variation in C. neoformans and clinically relevant phenotypes and animal model pathogenesis, thereby shedding light on specific survival mechanisms within the CNS and identifying the pathways involved in yeast persistence. IMPORTANCE Infection outcomes for cryptococcosis, most commonly caused by C. neoformans, are influenced by host immune responses as well as by host and pathogen genetics. Infecting yeast isolates are genetically diverse; however, we lack a deep understanding of how this diversity impacts patient outcomes. To better understand both clinical isolate diversity and how diversity contributes to infection outcomes, we utilize a large collection of clinical C. neoformans samples that were isolated from patients enrolled in a clinical trial across 3 hospitals in Malawi. By combining whole-genome sequence data, clinical data, and in vitro growth data, we utilize genome-wide association approaches to examine the genetic basis of virulence. Genes with significant associations display virulence attributes in both murine and rabbit models, demonstrating that our approach can identify potential links between genetic variants and patho-biologically significant phenotypes.
| S-EPMC9765290 | biostudies-literature
Project description:Results from data on > 1000 haplotypes distributed over a nine-year period from a natural population of the microcrustacean Daphnia pulex reveal evolutionary-genomic features at a refined scale, including key population-genetic properties that are obscured in studies with smaller sample sizes. Background selection, resulting from the recurrent introduction of deleterious alleles, appears to strongly influence the dynamics of neutral alleles, inducing indirect negative selection on rare variants and positive selection on common variants. Fluctuating selection increases the persistence of nonsynonymous alleles with intermediate frequencies, while reducing standing levels of variation at linked silent sites. Combined with the results from an equally large metapopulation survey of the study species, regions of gene structure that are under strong purifying selection and classes of genes that are under strong positive selection in this key species can be confidently identified. Most notable among rapidly evolving Daphnia genes are those associated with ribosomes, mitochondrial functions, sensory systems, and lifespan determination.
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Project description:The relationship between population size, inbreeding, loss of genetic variation and evolutionary potential of fitness traits is still unresolved, and large-scale empirical studies testing theoretical expectations are surprisingly scarce. Here we present a highly replicated experimental evolution setup with 120 lines of Drosophila melanogaster having experienced inbreeding caused by low population size for a variable number of generations. Genetic variation in inbred lines and in outbred control lines was assessed by genotyping-by-sequencing (GBS) of pooled samples consisting of 15 males per line. All lines were reared on a novel stressful medium for 10 generations during which body mass, productivity, and extinctions were scored in each generation. In addition, we investigated egg-to-adult viability in the benign and the stressful environments before and after rearing at the stressful conditions for 10 generations. We found strong positive correlations between levels of genetic variation and evolutionary response in all investigated traits, and showed that genomic variation was more informative in predicting evolutionary responses than population history reflected by expected inbreeding levels. We also found that lines with lower genetic diversity were at greater risk of extinction. For viability, the results suggested a trade-off in the costs of adapting to the stressful environments when tested in a benign environment. This work presents convincing support for long-standing evolutionary theory, and it provides novel insights into the association between genetic variation and evolutionary capacity in a gradient of diversity rather than dichotomous inbred/outbred groups.
| S-EPMC6590832 | biostudies-literature
Project description:Haemonchus contortus is a globally distributed and economically important gastrointestinal pathogen of small ruminants and has become a key nematode model for studying anthelmintic resistance and other parasite-specific traits among a wider group of parasites including major human pathogens. Here, we report using PacBio long-read and OpGen and 10X Genomics long-molecule methods to generate a highly contiguous 283.4 Mbp chromosome-scale genome assembly including a resolved sex chromosome for the MHco3(ISE).N1 isolate. We show a remarkable pattern of conservation of chromosome content with Caenorhabditis elegans, but almost no conservation of gene order. Short and long-read transcriptome sequencing allowed us to define coordinated transcriptional regulation throughout the parasite's life cycle and refine our understanding of cis- and trans-splicing. Finally, we provide a comprehensive picture of chromosome-wide genetic diversity both within a single isolate and globally. These data provide a high-quality comparison for understanding the evolution and genomics of Caenorhabditis and other nematodes and extend the experimental tractability of this model parasitic nematode in understanding helminth biology, drug discovery and vaccine development, as well as important adaptive traits such as drug resistance.
| S-EPMC7652881 | biostudies-literature
Project description:Banana (Musa spp.) is an important crop in the African Great Lakes region in terms of income and food security, with the highest per capita consumption worldwide. Pests, diseases and climate change hamper sustainable production of bananas. New breeding tools with increased crossbreeding efficiency are being investigated to breed for resistant, high yielding hybrids of East African Highland banana (EAHB). These include genomic selection (GS), which will benefit breeding through increased genetic gain per unit time. Understanding trait variation and the correlation among economically important traits is an essential first step in the development and selection of suitable GS models for banana. In this study, we tested the hypothesis that trait variations in bananas are not affected by cross combination, cycle, field management and their interaction with genotype. A training population created using EAHB breeding material and its progeny was phenotyped in two contrasting conditions. A high level of correlation among vegetative and yield related traits was observed. Therefore, genomic selection models could be developed for traits that are easily measured. It is likely that the predictive ability of traits that are difficult to phenotype will be similar to less difficult traits they are highly correlated with. Genotype response to cycle and field management practices varied greatly with respect to traits. Yield related traits accounted for 31-35% of principal component variation under low and high input field management conditions. Resistance to Black Sigatoka was stable across cycles but varied under different field management depending on the genotype. The best cross combination was 1201K-1xSH3217 based on selection response (R) of hybrids. Genotyping using simple sequence repeat (SSR) markers revealed that the training population was genetically diverse, reflecting a complex pedigree background, which was mostly influenced by the male parents.
| S-EPMC5460855 | biostudies-literature