Characterizing Pareto fronts: Trade-offs in the yeast growth cycle constrain adaptation
Characterizing Pareto fronts: Trade-offs in the yeast growth cycle constrain adaptation
批准号:
10749856
负责人:
JASON Alexander TARKINGTON
金额:
$7.43万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2024
资助国家:
美国
项目状态:
未结题
起止时间:
2024-01-17 至 2025-01-16
关键词:
Antineoplastic AgentsBar CodesBiological AssayBiophysical ProcessCarbonCommunicable DiseasesDNADataDimensionsDrug resistanceDrug usageEnvironmentEthanolEvolutionExperimental DesignsExtinctionFermentationFreedomFutureGeneticGenetic EpistasisGenotypeGlucoseGlycerolGrowthHeterogeneityLeadMapsMeasurementMeasuresMicrobeMolecularMutationNatural SelectionsOrganismOutcomePatternPerformancePharmaceutical PreparationsPhasePhenotypePopulationPopulation PressuresProcessRecording of previous eventsResearch PersonnelRespirationRoleRouteSamplingSeasonal VariationsShapesSourceSpecialistStochastic ProcessesTimeWorkYeastsantimicrobial drugcancer cellcostdesignexperiencefitnessgenome sequencingglobal healthimprovedinsightmutantpleiotropismpreventresponsetraittumor progressionwhole genomeyeast genome
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英文摘要
Project Summary/Abstract
Adaptive evolution involves optimizing multiple fitness related traits simultaneously. These traits can be
projected into a multidimensional space known as trait space. Mapping the trait space accessible by single
mutations can reveal the constraints imposed on organismal fitness. The fitness of an organism in an
environment is often dependent on more than one trait; for yeast these traits include fermentation,
respiration, and stationary phase performance. While in some cases it may be possible to improve
multiple fitness related traits independently, certain fitness-related traits can also be constrained due to the
pleiotropic effects of other fitness related traits, resulting in a trade-off. Previous work from the Sherlock lab
has shown that following evolution in a glucose-containing, carbon-limited medium, that Pareto fronts,
indicative of underlying trade-offs, emerge between stationary phase and respiration, and between respiration
and fermentation, though not between stationary phase and fermentation. Here, I aim to understand the
constraints on fitness in the yeast growth cycle and why such trade-offs emerge among some fitness-related
traits but not others. I will evolve barcoded yeast in a non-fermentable carbon source with varying amounts of
time spent in stationary phase. This experimental design eliminates selection for fermentation entirely and
creates varying degrees of selection for performance in respiration and stationary phase e.g., the two-day
transfer regime selects primarily for respiration performance, while in the 10-day transfer regime stationary
phase performance will be more important. Under these conditions stationary phase performance may be free
to increase unconstrained by fermentation performance resulting in the emergence of a pareto front between
these components of organismal fitness. Freedom from fermentation performance constraints may also allow
yeast to maximize respiration and stationary phase performances simultaneously. In addition to phenotypic
analysis, I will also characterize the molecular basis of the underlying adaptive mutations that emerge to gain
insight into the biophysical mechanism(s) preventing multiple traits from being optimized simultaneously.
Finally, I will further evolve specific adaptive mutants to gain insight into the role of contingency in
determining adaptive outcomes and determine whether specialists for one trait are limited in their future
evolutionary trajectories when selected for improvement of a different trait.
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