(角度)阻塞压力反应更好的记忆?

Two years ago, a small molecule was discovered that enhanced the memory of rodents (1). Pinpointing the target of this compound, called integrated stress response inhibitor (ISRIB), could guide the development of cognitive disorder treatments. Two groups have now identified a target. On page 1027 of this issue, Sekine et al. (2) report, as do Sidrauski et al. (3), that ISRIB increases the activity of eukaryotic translation initiation factor 2B (eIF2B), a factor that regulates protein synthesis in a pathway underlying the cellular response to stress.

• http://www.sciencemag.org/content/348/6238/967.abstract?rss=1

[详细]

(角度)克服kinetoplastid疾病的忽视

Of the 17 neglected tropical diseases listed by the World Health Organization (WHO) (1), three are caused by parasitic kinetoplastid protozoa: human African trypanosomiasis (HAT; also known as sleeping sickness), leishmaniasis, and Chagas disease. The three diseases are responsible for high mortality and morbidity among the world's poorest populations. Although these and other neglected diseases have received increased attention over the past decade, new drugs are still scarce: From 2000 to 2011, only 4% of new drugs and vaccines were registered for neglected diseases (2). However, the drug development pipeline, with sustained resources and research efforts, should see the delivery of new drugs for these diseases over the next decade.

• http://www.sciencemag.org/content/348/6238/974.abstract?rss=1

[详细]

(角度)灵活的基因库

Evolution acts to shape genetic variation within populations. However, in microbial communities, it is often surprisingly difficult to characterize what the “population” actually represents. This makes it hard to interpret the diversity often observed in microbial communities. To what extent is diversity within a microbial species (or operational taxonomic unit, typically defined to span ~3% 16S rRNA sequence divergence) representative of one population occupying a single ecological niche? Do multiple sequence clusters in a given population represent distinct functionally diverse strains? And by how much does genetic exchange blur the boundaries of strains and species? On page 1019 of this issue, Rosen et al. (1) show that rapid genetic exchange maintains extensive diversity of mosaic genomes in a cyanobacterial biofilm community, despite the action of selection on many individual loci.

• http://www.sciencemag.org/content/348/6238/977.abstract?rss=1

[详细]

(编辑选择)向更好地控制基因组编辑

Author: Valda Vinson

• http://www.sciencemag.org/content/348/6238/986.5.full?rss=1

[详细]

[研究]条结构依据能量转移途径在植物PSI-LHCI supercomplex

Photosynthesis converts solar energy to chemical energy by means of two large pigment-protein complexes: photosystem I (PSI) and photosystem II (PSII). In higher plants, the PSI core is surrounded by a large light-harvesting complex I (LHCI) that captures sunlight and transfers the excitation energy to the core with extremely high efficiency. We report the structure of PSI-LHCI, a 600-kilodalton membrane protein supercomplex, from Pisum sativum (pea) at a resolution of 2.8 angstroms. The structure reveals the detailed arrangement of pigments and other cofactors—especially within LHCI—as well as numerous specific interactions between the PSI core and LHCI. These results provide a firm structural basis for our understanding on the energy transfer and photoprotection mechanisms within the PSI-LHCI supercomplex.

• http://www.sciencemag.org/content/348/6238/989.abstract?rss=1

[详细]

[报告]合成和表征P2N3−:一个芳香离子组成的磷和氮

Aromaticity is predominantly associated with carbon-rich compounds but can also occur in all-inorganic ones. We report the synthesis of the diphosphatriazolate anion, a rare example of a planar aromatic inorganic species. Treatment of azide (N3−) in tetrahydrofuran solution with P2A2 (A = C14H10), a source of P2, produced P2N3−, which we isolated as its [Na-kryptofix-221]+ salt in 22% yield and characterized by single-crystal x-ray diffraction. Salts [Na-kryptofix-221] [P2N3] and [Na-kryptofix-221] [P215NN2] were analyzed by infrared and Raman spectroscopy, 15N and 31P nuclear magnetic resonance spectroscopy, and mass spectrometry. The formation of the P2N3− anion was investigated using density functional theory, and its aromatic character was confirmed by NICS (nucleus-independent chemical shift) and QTAIM (quantum theory of atoms in molecules) methods.

• http://www.sciencemag.org/content/348/6238/1001.summary?rss=1

[详细]

[报告]做精密的多样性和广泛的重组quasisexual细菌人口占据一个广泛的生态位

Extensive fine-scale genetic diversity is found in many microbial species across varied environments, but for most, the evolutionary scenarios that generate the observed variation remain unclear. Deep sequencing of a thermophilic cyanobacterial population and analysis of the statistics of synonymous single-nucleotide polymorphisms revealed a high rate of homologous recombination and departures from neutral drift consistent with the effects of genetic hitchhiking. A sequenced isolate genome resembled an unlinked random mixture of the allelic diversity at the sampled loci. These observations suggested a quasisexual microbial population that occupies a broad ecological niche, with selection driving frequencies of alleles rather than whole genomes.

• http://www.sciencemag.org/content/348/6238/1019.summary?rss=1

[详细]

[报告]转录因子GABP选择性结合并激活癌症突变叔子

Reactivation of telomerase reverse transcriptase (TERT) expression enables cells to overcome replicative senescence and escape apoptosis, which are fundamental steps in the initiation of human cancer. Multiple cancer types, including up to 83% of glioblastomas (GBMs), harbor highly recurrent TERT promoter mutations of unknown function but specific to two nucleotide positions. We identified the functional consequence of these mutations in GBMs to be recruitment of the multimeric GA-binding protein (GABP) transcription factor specifically to the mutant promoter. Allelic recruitment of GABP is consistently observed across four cancer types, highlighting a shared mechanism underlying TERT reactivation. Tandem flanking native E26 transformation-specific motifs critically cooperate with these mutations to activate TERT, probably by facilitating GABP heterotetramer binding. GABP thus directly links TERT promoter mutations to aberrant expression in multiple cancers.

• http://www.sciencemag.org/content/348/6238/1036.summary?rss=1

[详细]

[报告]cysteine-clamp基因驱动胚胎极性的蚊摇蚊属

In the fruit fly Drosophila, head formation is driven by a single gene, bicoid, which generates head-to-tail polarity of the main embryonic axis. Bicoid deficiency results in embryos with tail-to-tail polarity and no head. However, most insects lack bicoid, and the molecular mechanism for establishing head-to-tail polarity is poorly understood. We have identified a gene that establishes head-to-tail polarity of the mosquito-like midge, Chironomus riparius. This gene, named panish, encodes a cysteine-clamp DNA binding domain and operates through a different mechanism than bicoid. This finding, combined with the observation that the phylogenetic distributions of panish and bicoid are limited to specific families of flies, reveals frequent evolutionary changes of body axis determinants and a remarkable opportunity to study gene regulatory network evolution.

• http://www.sciencemag.org/content/348/6238/1040.summary?rss=1

[详细]

(商务办公功能)成瘾研究进展:应用基因生物标记个性化治疗

Advancements in genetics, sequencing technology, and bioinformatics are changing the principles of current medical practice and transforming the standards of patient care. Genetic detection of common and rare variants within populations provides valuable information about predisposition and vulnerability to complex human disease. Data from large-scale genome-wide association studies have identified genetic variations correlated to biological events, enabling combinations of genetic and non-genetic markers to be translated into potential diagnostic tools. However, aspects of these programs are still evolving, including best practices for protocol development, sample processing, genetic/genomic analysis, data management, and quality control. In this webinar, our expert panel will discuss how to better define these procedures and maximize the use of precious, limited clinical samples by utilizing recent innovations, advances in technology, and current best practices.View the Webinar

• http://www.sciencemag.org/content/348/6238/1044.3.summary?rss=1

[详细]

[工作]所有的家庭

Author: Rachel Bernstein

• http://www.sciencemag.org/content/348/6238/1050.summary?rss=1

[详细]

歧视在PCNA-immunolabeled细胞细胞周期的阶段

Background: Protein function in eukaryotic cells is often controlled in a cell cycle-dependent manner. Therefore, the correct assignment of cellular phenotypes to cell cycle phases is a crucial task in cell biology research. Nuclear proteins whose localization varies during the cell cycle are valuable and frequently used markers of cell cycle progression. Proliferating cell nuclear antigen (PCNA) is a protein which is involved in DNA replication and has cell cycle dependent properties. In this work, we present a tool to identify cell cycle phases and in particular, sub-stages of the DNA replication phase (S-phase) based on the characteristic patterns of PCNA distribution. Single time point images of PCNA-immunolabeled cells are acquired using confocal and widefield fluorescence microscopy. In order to discriminate different cell cycle phases, an optimized processing pipeline is proposed. For this purpose, we provide an in-depth analysis and selection of appropriate features for classification, an in-depth evaluation of different classification algorithms, as well as a comparative analysis of classification performance achieved with confocal versus widefield microscopy images. Results: We show that the proposed processing chain is capable of automatically classifying cell cycle phases in PCNA-immunolabeled cells from single time point images, independently of the technique of image acquisition. Comparison of confocal and widefield images showed that for the proposed approach, the overall classification accuracy is slightly higher for confocal microscopy images. Conclusion: Overall, automated identification of cell cycle phases and in particular, sub-stages of the DNA replication phase (S-phase) based on the characteristic patterns of PCNA distribution, is feasible for both confocal and widefield images.

• http://www.biomedcentral.com/1471-2105/16/180

[详细]

热力学和水平基因转移后恢复治理演化动力学

Shared host cells can serve as melting pots for viral genomes, giving many phylogenies a web-like appearance due to horizontal gene transfer. However, not all virus families exhibit web-like phylogenies. Microviruses form three distinct clades, represented by X174, G4, and α3. Here, we investigate protein-based barriers to horizontal gene transfer between clades. We transferred gene G, which encodes a structural protein, between X174 and G4, and monitored the evolutionary recovery of the resulting chimeras. In both cases, particle assembly was the major barrier after gene transfer. The G4XG chimera displayed a temperature-sensitive assembly defect that could easily be corrected via single mutations that promote productive assembly. Gene transfer in the other direction was more problematic. The initial XG4G chimera required an exogenous supply of both the X174 major spike G and DNA pilot H proteins. Elevated DNA pilot protein levels may be required to compensate for off-pathway reactions that may have become thermodynamically and/or kinetically favored when the foreign spike protein was present. After three targeted genetic selections, the foreign spike protein was productively integrated into the X174 background. The first adaption involved a global decrease in gene expression. This was followed by modifications affecting key protein-protein interactions that govern assembly. Finally, gene expression was re-elevated. While the first selection suppresses non-productive reactions, subsequent selections promote productive assembly and ultimately viability. However, viable chimeric strains exhibited reduced fitness compared to wild-type. This chimera’s path to recovery may partially explain how unusual recombinant viruses could persist long enough to naturally emerge.

• http://mbe.oxfordjournals.org/cgi/content/short/msv130v1?rss=1

[详细]

自动带注释的RNA结构探测与大量的毛细管电泳实验资料

Motivation: Capillary electrophoresis (CE) is a powerful approach for structural analysis of nucleic acids, with recent high-throughput variants enabling three-dimensional RNA modeling and the discovery of new rules for RNA structure design. Among the steps composing CE analysis, the process of finding each band in an electrophoretic trace and mapping it to a position in the nucleic acid sequence has required significant manual inspection and remains the most time-consuming and error-prone step. The few available tools seeking to automate this band annotation have achieved limited accuracy and have not taken advantage of information across dozens of profiles routinely acquired in high-throughput measurements.

Results: We present a dynamic-programming-based approach to automate band annotation for high-throughput capillary electrophoresis. The approach is uniquely able to define and optimize a robust target function that takes into account multiple CE profiles (sequencing ladders, different chemical probes, different mutants) collected for the RNA. Over a large benchmark of multi-profile datasets for biological RNAs and designed RNAs from the EteRNA project, the method outperforms prior tools (QuSHAPE and FAST) significantly in terms of accuracy compared with gold-standard manual annotations. The amount of computation required is reasonable at a few seconds per dataset. We also introduce an ‘E-score’ metric to automatically assess the reliability of the band annotation and show it to be practically useful in flagging uncertainties in band annotation for further inspection.

Availability and implementation: The implementation of the proposed algorithm is included in the HiTRACE software, freely available as an online server and for download at http://hitrace.stanford.edu.

Contact: sryoon@snu.ac.kr or rhiju@stanford.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv282v2?rss=1

[详细]

差异蛋白质表达和峰的质谱数据选择二进制判别分析

Motivation: Proteomic mass spectrometry analysis is becoming routine in clinical diagnostics, for example to monitor cancer biomarkers using blood samples. However, differential proteomics and identification of peaks relevant for class separation remains challenging.

Results: Here, we introduce a simple yet effective approach for identifying differentially expressed proteins using binary discriminant analysis. This approach works by data-adaptive thresholding of protein expression values and subsequent ranking of the dichotomized features using a relative entropy measure. Our framework may be viewed as a generalization of the ‘peak probability contrast’ approach of Tibshirani et al. (2004) and can be applied both in the two-group and the multi-group setting.

Our approach is computationally inexpensive and shows in the analysis of a large-scale drug discovery test data set equivalent prediction accuracy as a random forest. Furthermore, we were able to identify in the analysis of mass spectrometry data from a pancreas cancer study biological relevant and statistically predictive marker peaks unrecognized in the original study.

Availability: The methodology for binary discriminant analysis is implemented in the R package binda, which is freely available under the GNU General Public License (version 3 or later) from CRAN at URL http://cran.r-project.org/web/packages/binda/. R scripts reproducing all described analyzes are available from the web page http://strimmerlab.org/software/binda/.

Contact: k.strimmer@imperial.ac.uk

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv334v1?rss=1

[详细]

王牌:准确使用K-mer尝试纠正错误

Summary: The quality of high-throughput next-generation sequencing data significantly influences the performance and memory consumption of assembly and mapping algorithms. The most ubiquitous platform, Illumina, mainly suffers from substitution errors. We have developed a tool, ACE, based on K-mer tries to correct such errors. On real MiSeq and HiSeq Illumina archives, ACE yields higher gains in terms of coverage depth, outperforming state-of-the-art competitors in the majority of cases.

Availability and implementation: ACE is licensed under the GPL license and can be freely obtained at https://github.com/sheikhizadeh/ACE/. The program is implemented in C++ and runs on most Unix-derived operating systems.

Supplementary information: available at Bioinformatics online.

Contact: siavash.sheikhizadehanari@wur.nl

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv332v1?rss=1

[详细]

Qvz先锋教育网：质量值的有损压缩

Motivation: Recent advancements in sequencing technology have led to a drastic reduction in the cost of sequencing a genome. This has generated an unprecedented amount of genomic data that must be stored, processed, and transmitted. To facilitate this effort, we propose a new lossy compressor for the quality values presented in genomic data files (e.g., FASTQ and SAM files), which comprise roughly half of the storage space (in the uncompressed domain). Lossy compression allows for compression of data beyond its lossless limit.

Results: The proposed algorithm QVZ exhibits better rate-distortion performance than the previously proposed algorithms, for several distortion metrics and for the lossless case. Moreover, it allows the user to define any quasi-convex distortion function to be minimized, a feature not supported by the previous algorithms. Finally, we show that QVZ-compressed data exhibits better performance in the genotyping than data compressed with previously proposed algorithms, in the sense that for a similar rate, a genotyping closer to that achieved with the original quality values is obtained.

Availability: QVZ is written in C and can be downloaded from https://github.com/mikelhernaez/qvz.

Contact: gmalysa@stanford.edu, mhernaez@stanford.edu, iochoa@stanford.edu, milind@stanford.edu, karthik3@stanford.edu, tsachy@stanford.edu

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv330v1?rss=1

[详细]

涤纶:模拟RNA-seq数据集与微分记录表达式

Motivation: Statistical methods development for differential expression analysis of RNA sequencing (RNA-seq) requires software tools to assess accuracy and error rate control. Since true differential expression status is often unknown in experimental datasets, artificially constructed datasets must be utilized, either by generating costly spike-in experiments or by simulating RNA-seq data.

Results: Polyester is an R package designed to simulate RNA-seq data, beginning with an experimental design and ending with collections of RNA-seq reads. Its main advantage is the ability to simulate reads indicating isoform-level differential expression across biological replicates for a variety of experimental designs. Data generated by Polyester is a reasonable approximation to real RNA-seq data and standard differential expression workflows can recover differential expression set in the simulation by the user.

Availability and implementation: Polyester is freely available from Bioconductor (http://bioconductor.org/).

Contact: jtleek@gmail.com

Supplementary information: Supplementary data are available at Bioinformatics online.

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv272v2?rss=1

[详细]

GEO2Enrichr browser:3 to app服务器和扩展的全球环境展望和analyze sets gene而后for生物页

Motivation: Identification of differentially expressed genes is an important step in extracting knowledge from gene expression profiling studies. The raw expression data from microarray and other high-throughput technologies is deposited into the Gene Expression Omnibus (GEO) and served as Simple Omnibus Format in Text (SOFT) files. However, to extract and analyze differentially expressed genes from GEO requires significant computational skills.

Results: Here we introduce GEO2Enrichr, a browser extension for extracting differentially expressed gene sets from GEO and analyzing those sets with Enrichr, an independent gene set enrichment analysis tool containing over 70 000 annotated gene sets organized into 75 gene-set libraries. GEO2Enrichr adds JavaScript code to GEO web-pages; this code scrapes user selected accession numbers and metadata, and then, with one click, users can submit this information to a web-server application that downloads the SOFT files, parses, cleans and normalizes the data, identifies the differentially expressed genes, and then pipes the resulting gene lists to Enrichr for downstream functional analysis. GEO2Enrichr opens a new avenue for adding functionality to major bioinformatics resources such GEO by integrating tools and resources without the need for a plug-in architecture. Importantly, GEO2Enrichr helps researchers to quickly explore hypotheses with little technical overhead, lowering the barrier of entry for biologists by automating data processing steps needed for knowledge extraction from the major repository GEO.

Availability and implementation: GEO2Enrichr is an open source tool, freely available for installation as browser extensions at the Chrome Web Store and FireFox Add-ons. Documentation and a browser independent web application can be found at http://amp.pharm.mssm.edu/g2e/.

Contact: avi.maayan@mssm.edu

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv297v2?rss=1

[详细]

利用复制的证据评价ChIP-seq峰值

Motivation: Chromatin Immunoprecipitation followed by sequencing (ChIP-seq) detects genome-wide DNA–protein interactions and chromatin modifications, returning enriched regions (ERs), usually associated with a significance score. Moderately significant interactions can correspond to true, weak interactions, or to false positives; replicates of a ChIP-seq experiment can provide co-localised evidence to decide between the two cases. We designed a general methodological framework to rigorously combine the evidence of ERs in ChIP-seq replicates, with the option to set a significance threshold on the repeated evidence and a minimum number of samples bearing this evidence.

Results: We applied our method to Myc transcription factor ChIP-seq datasets in K562 cells available in the ENCODE project. Using replicates, we could extend up to 3 times the ER number with respect to single-sample analysis with equivalent significance threshold. We validated the ‘rescued’ ERs by checking for the overlap with open chromatin regions and for the enrichment of the motif that Myc binds with strongest affinity; we compared our results with alternative methods (IDR and jMOSAiCS), obtaining more validated peaks than the former and less peaks than latter, but with a better validation.

Availability and implementation: An implementation of the proposed method and its source code under GPLv3 license are freely available at http://www.bioinformatics.deib.polimi.it/MSPC/ and http://mspc.codeplex.com/, respectively.

Contact: marco.morelli@iit.it

Supplementary information: Supplementary Material are available at Bioinformatics online.

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv293v2?rss=1

[详细]

输入:预测从序列非同义变体对蛋白质稳定性的影响

Motivation: A tool for reliably predicting the impact of variations on protein stability is extremely important for both protein engineering and for understanding the effects of Mendelian and somatic mutations in the genome. Next Generation Sequencing studies are constantly increasing the number of protein sequences. Given the huge disproportion between protein sequences and structures, there is a need for tools suited to annotate the effect of mutations starting from protein sequence without relying on the structure. Here, we describe INPS, a novel approach for annotating the effect of non-synonymous mutations on the protein stability from its sequence. INPS is based on SVM regression and it is trained to predict the thermodynamic free energy change upon single-point variations in protein sequences.

Results: We show that INPS performs similarly to the state-of-the-art methods based on protein structure when tested in cross-validation on a non-redundant dataset. INPS performs very well also on a newly generated dataset consisting of a number of variations occurring in the tumor suppressor protein p53. Our results suggest that INPS is a tool suited for computing the effect of non-synonymous polymorphisms on protein stability when the protein structure is not available. We also show that INPS predictions are complementary to those of the state-of-the-art, structure-based method mCSM. When the two methods are combined, the overall prediction on the p53 set scores significantly higher than those of the single methods.

Availability and implementation: The presented method is available as web server at http://inps.biocomp.unibo.it.

Contact: piero.fariselli@unibo.it

Supplementary information: Supplementary Materials are available at Bioinformatics online.

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv291v2?rss=1

[详细]

随着时间的推移降低非氨基酸的收敛速度

Convergence is a central concept in evolutionary studies because it provides strong evidence for adaptation. It also provides information about the nature of the fitness landscape and the repeatability of evolution, and can mislead phylogenetic inference. To understand the role of adaptive convergence, we need to understand the patterns of nonadaptive convergence. Here, we consider the relationship between nonadaptive convergence and divergence in mitochondrial and model proteins. Surprisingly, nonadaptive convergence is much more common than expected in closely related organisms, falling off as organisms diverge. The extent of the convergent drop-off in mitochondrial proteins is well predicted by epistatic or coevolutionary effects in our "evolutionary Stokes shift" models and poorly predicted by conventional evolutionary models. Convergence probabilities decrease dramatically if the ancestral amino acids of branches being compared have diverged, but also drop slowly over evolutionary time even if the ancestral amino acids have not substituted. Convergence probabilities drop-off rapidly for quickly evolving sites, but much more slowly for slowly evolving sites. Furthermore, once sites have diverged their convergence probabilities are extremely low and indistinguishable from convergence levels at randomized sites. These results indicate that we cannot assume that excessive convergence early on is necessarily adaptive. This new understanding should help us to better discriminate adaptive from nonadaptive convergence and develop more relevant evolutionary models with improved validity for phylogenetic inference.

• http://mbe.oxfordjournals.org/cgi/content/short/32/6/1373?rss=1

[详细]

一个广泛的同源四倍体拟南芥arenosa谱系随后interploidy外加剂单地理起源

Whole-genome duplication, which leads to polyploidy, has been implicated in speciation and biological novelty. In plants, many species exhibit ploidy variation, which is likely representative of an early stage in the evolution of polyploid lineages. To understand the evolution of such multiploidy systems, we must address questions such as whether polyploid lineage(s) had a single or multiple origins, whether admixture occurs between ploidies, and the timescale over which ploidy variation affects the evolution of populations. Here we analyze three genomic data sets using nonparametric and parametric analyses, including coalescent-based methods, to study the evolutionary history of a geographically widespread autotetraploid variant of Arabidopsis arenosa, a new model system for understanding the molecular basis of autopolyploid evolution. Autotetraploid A. arenosa populations are widely distributed across much of Northern and Central Europe, whereas diploids occur in Eastern Europe and along the southern Baltic coast; the two ploidies overlap in the Carpathian Mountains. We find that the widespread autotetraploid populations we sampled likely arose from a single ancestral population approximately 11,000–30,000 generations ago in the Northern Carpathians, where its closest extant diploid relatives are found today. Afterward, the tetraploid population split into at least four major lineages that colonized much of Europe. Reconstructions of population history suggest that substantial interploidy admixture occurred in both directions, but only among geographically proximal populations. We find two cases in which selection likely acted on an introgressed locus, suggesting that persistent interploidy gene flow has a local influence on patterns of genetic variation in A. arenosa.

• http://mbe.oxfordjournals.org/cgi/content/short/32/6/1382?rss=1

[详细]

流行克隆，海洋基因库，并在自由生活海洋病原菌副溶血性弧菌生态LD

We investigated global patterns of variation in 157 whole-genome sequences of Vibrio parahaemolyticus, a free-living and seafood associated marine bacterium. Pandemic clones, responsible for recent outbreaks of gastroenteritis in humans, have spread globally. However, there are oceanic gene pools, one located in the oceans surrounding Asia and another in the Mexican Gulf. Frequent recombination means that most isolates have acquired the genetic profile of their current location. We investigated the genetic structure in the Asian gene pool by calculating the effective population size in two different ways. Under standard neutral models, the two estimates should give similar answers but we found a 27-fold difference. We propose that this discrepancy is caused by the subdivision of the species into a hundred or more ecotypes which are maintained stably in the population. To investigate the genetic factors involved, we used 51 unrelated isolates to conduct a genome-wide scan for epistatically interacting loci. We found a single example of strong epistasis between distant genome regions. A majority of strains had a type VI secretion system associated with bacterial killing. The remaining strains had genes associated with biofilm formation and regulated by cyclic dimeric GMP signaling. All strains had one or other of the two systems and none of isolate had complete complements of both systems, although several strains had remnants. Further "top down" analysis of patterns of linkage disequilibrium within frequently recombining species will allow a detailed understanding of how selection acts to structure the pattern of variation within natural bacterial populations.

• http://mbe.oxfordjournals.org/cgi/content/short/32/6/1396?rss=1

[详细]