Vibrio cholerae is a globally dispersed pathogen that has evolved with humans for centuries, but also includes non-pathogenic environmental strains. Here, we identify the genomic variability underlying this remarkable persistence across the three major niche dimensions space, time, and habitat.
Results
Taking an innovative approach of genome-wide association applicable to microbial genomes (GWAS-M), we classify 274 complete V. cholerae genomes by niche, including 39 newly sequenced for this study with the Ion Torrent DNA-sequencing platform. Niche metadata were collected for each strain and analyzed together with comprehensive annotations of genetic and genomic attributes, including point mutations (single-nucleotide polymorphisms, SNPs), protein families, functions and prophages.
Conclusions
Our analysis revealed that genomic variations, in particular mobile functions including phages, prophages, transposable elements, and plasmids underlie the metadata structuring in each of the three niche dimensions. This underscores the role of phages and mobile elements as the most rapidly evolving elements in bacterial genomes, creating local endemicity (space), leading to temporal divergence (time), and allowing the invasion of new habitats. Together, we take a data-driven approach for comparative functional genomics that exploits high-volume genome sequencing and annotation, in conjunction with novel statistical and machine learning analyses to identify connections between genotype and phenotype on a genome-wide scale.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-654) contains supplementary material, which is available to authorized users. 相似文献
Bipolar disorder is a common, heritable mental illness characterized by recurrent episodes of mania and depression. Despite considerable effort to elucidate the genetic underpinnings of bipolar disorder, causative genetic risk factors remain elusive. We conducted a comprehensive genomic analysis of bipolar disorder in a large Old Order Amish pedigree. Microsatellite genotypes and high-density SNP-array genotypes of 388 family members were combined with whole genome sequence data for 50 of these subjects, comprising 18 parent-child trios. This study design permitted evaluation of candidate variants within the context of haplotype structure by resolving the phase in sequenced parent-child trios and by imputation of variants into multiple unsequenced siblings. Non-parametric and parametric linkage analysis of the entire pedigree as well as on smaller clusters of families identified several nominally significant linkage peaks, each of which included dozens of predicted deleterious variants. Close inspection of exonic and regulatory variants in genes under the linkage peaks using family-based association tests revealed additional credible candidate genes for functional studies and further replication in population-based cohorts. However, despite the in-depth genomic characterization of this unique, large and multigenerational pedigree from a genetic isolate, there was no convergence of evidence implicating a particular set of risk loci or common pathways. The striking haplotype and locus heterogeneity we observed has profound implications for the design of studies of bipolar and other related disorders. 相似文献
Growth condition perturbation or gene function disruption are commonly used strategies to study cellular systems. Although it is widely appreciated that such experiments may involve indirect effects, these frequently remain uncharacterized. Here, analysis of functionally unrelated Saccharyomyces cerevisiae deletion strains reveals a common gene expression signature. One property shared by these strains is slower growth, with increased presence of the signature in more slowly growing strains. The slow growth signature is highly similar to the environmental stress response (ESR), an expression response common to diverse environmental perturbations. Both environmental and genetic perturbations result in growth rate changes. These are accompanied by a change in the distribution of cells over different cell cycle phases. Rather than representing a direct expression response in single cells, both the slow growth signature and ESR mainly reflect a redistribution of cells over different cell cycle phases, primarily characterized by an increase in the G1 population. The findings have implications for any study of perturbation that is accompanied by growth rate changes. Strategies to counter these effects are presented and discussed. 相似文献
In utero microinjection has proven valuable for exploring the developmental consequences of altering gene expression, and
for studying cell lineage or migration during the latter half of embryonic mouse development (from embryonic day 9.5 of gestation
(E9.5)). In the current study, we use ultrasound guidance to accurately target microinjections in the conceptus at E6.5–E7.5,
which is prior to cardiovascular or placental dependence. This method may be useful for determining the developmental effects
of targeted genetic or cellular interventions at critical stages of placentation, gastrulation, axis formation, and neural
tube closure. 相似文献
The qualitative and quantitative carotenoid composition of seven prasinophytes (eight clones) have been examined by chromatographic (TLC and HPLC) and spectroscopic methods (VIS, CD and mass spectra).
The prasinophytes studied fall into two pigment types: (A) those producing common green algal carotenoids (β,β-carotene, β,ε-carotene, lutein, zeaxanthin and the epoxides violaxanthin and neoxanthin) and (B) prasinophytes synthesising carotenoids peculiar to this algal class (prasinoxanthin, anhydroprasinoxanthin, uriolide, anhydrouriolide, micromonal, anhydromicromonal, micromonol, anhydromicromonol and dihydrolutein), where prasinoxanthin is a major carotenoid.
Mantoniella squamata (clone 2) was grown under both low and high light intensity, revealing differences in carotenoid composition. Lutein together with lesser amounts of zeaxanthin and its epoxides were only detected at high light intensity.
Three previously unidentified carotenoids were identified as prasinoxanthin (xanthophyll K), micromonal and dihydrolutein. 相似文献
Journal of Applied Phycology - Botryococcus braunii CCAP 807/2 has been studied intensively for biofuel production due to its high hydrocarbon content. This strain is also capable of producing high... 相似文献
Bathycoccus prasinos Eikrem et Throndsen exhibited a complex carotenoid distribution pattern including the carotenes β,β-carotene (0.8% of total carotenoids) and β, ° Carotene (0.4%) and several xanthophylls. These were prasinoxanthin (49% of total carotenoids), micromonal (16%), neoxanthin (14%), uriolide (7%), violaxanthin (0.8%), 31-dehydrouriolide (0.8%), dihydrolutein (0.1%), two partly characterized esterified carotenols (together 10%), and five minor unidentified carotenols (together 2%). The identifications were based on high-performance liquid chromatography (HPLC), thin-layer chromatography (TLC), visible spectroscopy (VIS), and mass spectra (MS) and in part on 1H nuclear magnetic resonance (NMR), circular dichroism (CD), and chemical derivatization. The carotenoid composition of B. prasinos was related to that of other prasinoxanthin / uriolide / micromonal-producing prasinophytes (Mantoniella squamata, Micromonas pusilla, and Pseudoscourfieldia marina). The relative distribution of chlorophylls (w/w) were chlorophyll a (chl a; 63%), chl b (31%), and an unknown chl c-like chlorophyll (7%) with spectral characteristics similar to magnesium 2,4-divinylphaeoporphyrin a, monomethyl ester, compatible with other prasinophytes. The chemosystematic data and ultrastructural characteristics for the order Mamiellales are discussed. We conclude that HPLC studies alone are insufficient for the identification and characterization of the carotenoids, including the minor carotenoids essential for biosynthetic/chemosystematic considerations. 相似文献