Identifying Mutations that Promote Microbial Evolvability
识别促进微生物进化的突变
基本信息
- 批准号:8217096
- 负责人:
- 金额:$ 24.48万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-03-01 至 2014-01-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAntibiotic ResistanceBacteriaBiological AssayBiomedical ResearchBiotechnologyCell physiologyChemosensitizationChronicCoculture TechniquesCollectionDefectDisease ProgressionEnvironmentEscherichia coliEventEvolutionFrequenciesGene AmplificationGene DeletionGeneticGenetic AnticipationGenetic DriftGenomeGenomic InstabilityGenotypeHumanIncidenceInfectionInstructionKnowledgeLaboratoriesLeadMeasuresMetabolicMetabolismMicrobeMicrosatellite RepeatsModelingMolecularMutationOrganismPhysiologicalPoint MutationPopulationPopulation DynamicsPopulation GeneticsRelative (related person)ReporterResearchSeriesSpeedStatistical MethodsSystems BiologyTestingTimeVariantabstractingcase findingexpectationexperiencefitnessgenome sequencingimprovedinnovationmathematical modelmicrobialmicroorganismpathogenresearch studysimulationsuccesstrend
项目摘要
Evolvability describes an organism's capacity for producing descendants that are better adapted to a given
environment. Mutations that elevate overall point mutation rates can make bacteria more evolvable under
certain circumstances and consequently speed the progression of chronic infections and increase the
incidence of antibiotic resistance. Little is currently known about how mutations affecting other cellular
processes impact microbial evolvability or about how evolvability typically varies as microorganisms
experience random mutations due to genetic drift or adapt by beneficial mutations to higher fitness.
The proposed research systematically investigates how different kinds of mutations affect the evolvability of
Escherichia coli in laboratory evolution experiments. The first aim is to test three strain series differing by
predominantly deleterious, beneficial, or random mutations to establish baseline expectations. The second
aim is to recover genotypes that eventually prevail over competitors of higher fitness because they are more
evolvable by chronicling mutation dynamics in evolution experiments using deep sequencing, highthroughput
genotyping, and deletion and microsatellite markers. The third aim is to construct chromosomal
reporters with selectable markers for measuring gene amplification and deletion rates. These reporters will
be used to isolate new kinds of genomic instability mutators and to examine whether a similar defect
potentiated the evolution of a rare metabolic innovation in a 20-year evolution experiment.
Throughout, evolvability will be measured on multiple time scales by comparing the initial divergence of
marker trajectories in replicate evolution experiments to population genetic simulations and by performing
co-culture competition assays between endpoint isolates and a reference strain. When a strain is found with
unusually high or low evolvability, the causal mutation will be identified by genome re-sequencing, and its
physiological consequences will be investigated to find out why it affects evolutionary potential.
进化性描述了一个有机体产生后代的能力,这些后代更好地适应给定的环境。
环境提高整体点突变率的突变可以使细菌在环境中更容易进化。
在某些情况下,从而加速慢性感染的进展,并增加
抗生素耐药性发生率。目前对突变如何影响其他细胞的知之甚少。
过程影响微生物的进化性或关于进化性通常如何随着微生物
由于遗传漂变而经历随机突变或通过有益突变适应更高的适应性。
该研究系统地研究了不同类型的突变如何影响
实验室进化实验中的大肠杆菌。第一个目的是测试三个不同的菌株系列,
主要是有害的,有益的或随机的突变,以建立基线预期。第二
目标是恢复最终战胜适应度更高的竞争对手的基因型,因为它们的基因型更多
通过使用深度测序、高通量、
基因分型、缺失和微卫星标记。第三个目标是构建染色体
用于测量基因扩增和缺失率的选择性标记。这些记者将
用于分离新的基因组不稳定性突变体,并检查是否存在类似的缺陷,
在20年的进化实验中,加强了一种罕见的代谢创新的进化。
在整个过程中,将通过比较
标记轨迹在重复进化实验种群遗传模拟和执行
终点分离株和参考菌株之间的共培养竞争试验。当发现一种菌株,
异常高或低的进化性,因果突变将通过基因组重新测序来鉴定,
生理后果将被调查,以找出为什么它会影响进化潜力。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jeffrey Evan Barrick其他文献
Jeffrey Evan Barrick的其他文献
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{{ truncateString('Jeffrey Evan Barrick', 18)}}的其他基金
Identifying Mutations that Promote Microbial Evolvability
识别促进微生物进化的突变
- 批准号:
8213191 - 财政年份:2009
- 资助金额:
$ 24.48万 - 项目类别:
A mechanistic model of bacteriophage T7 infection, replication, and evolution
噬菌体 T7 感染、复制和进化的机制模型
- 批准号:
10624298 - 财政年份:2009
- 资助金额:
$ 24.48万 - 项目类别:
Identifying Mutations that Promote Microbial Evolvability
识别促进微生物进化的突变
- 批准号:
7644063 - 财政年份:2009
- 资助金额:
$ 24.48万 - 项目类别:
Identifying Mutations that Promote Microbial Evolvability
识别促进微生物进化的突变
- 批准号:
8413011 - 财政年份:2009
- 资助金额:
$ 24.48万 - 项目类别:
A mechanistic model of bacteriophage T7 infection, replication, and evolution
噬菌体 T7 感染、复制和进化的机制模型
- 批准号:
10406315 - 财政年份:2009
- 资助金额:
$ 24.48万 - 项目类别:
A mechanistic model of bacteriophage T7 infection, replication, and evolution
噬菌体 T7 感染、复制和进化的机制模型
- 批准号:
10224216 - 财政年份:2009
- 资助金额:
$ 24.48万 - 项目类别:
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