Rapid evolutionary adaptation is the foundational process in biology and at the core of many problems facing humanity, including cancer, bacterial and viral diseases, evolution of drug and pesticide resistance, and biological response to global change. This project aims to build predictive understanding of rapid evolution in an outbred, sexual organism in natural habitats by generating large-scale datasets of genotypic and phenotypic evolution on seasonal timescales (~10-20 generations) of the genetic model Drosophila melanogaster. The project follows previous work in which it was established that D. melanogaster populations in several temperate populations on the East Coast of North America cycle phenotypically for a number of fitness-related traits and genotypically at hundreds of SNPs. This project aims to test whether these patterns reflect the action of strong, local directional selection or whether they are due primarily to biased sampling and recurrent migration from refugia. In order to distinguish between these two scenarios the project will use a three-pronged approach. First, large-scale field seasonal collections across 20+ locations in North America and Europe combined with deep pooled resequencing of the collections, phenotyping of a subset of flies, and environmental monitoring will provide a fine map of the tempo and mode of phenotypic and genotyping evolution across space and environmental variation. Second, the project will employ highly replicated field mesocosms in an experimental orchard to directly observe phenotypic and genotypic evolution of D. melanogaster in a way that eliminates migration as a possible source of evolution. The experimental mesocosms will be initiated from two large outbred populations initiated from either a set of ~150 inbred and sequenced strains that were or from ~10,000 inbred lines generated by this project. Phenotyping and pooled resequencing will allow fine-mapping of genotype to phenotype, genotype to fitness, and phenotype to fitness to the best extent currently feasible. Finally, the project will investigate the phenotypic effects of ~50 seasonal SNPs that cycle robustly in the field and in the experimental mesocosms and that match to the best extent possible the genomic and population genetic properties of seasonal SNPs overall. The phenotypic tests across a large panel of fitness-related phenotypes will be carried out using outbred, indoor cages that are fixed for the alternate states of the seasonal SNPs in question and using genomic editing using CRISPR/Cas9 technology in two common genetic backgrounds. Upon completion of the three aims the project will generate the most comprehensive analysis and data to date of genotypic and phenotypic rapid evolution in a natural environmental context for any outbred, sexual organism.

Public Health Relevance

Using the model organism Drosophila melanogaster, this project seeks to determine fundamental dynamics of rapid adaptation in natural populations. Understanding the causes, mechanisms and consequences of rapid adaptation is of direct relevance to a number of biological phenomena including the dynamics of cancer, vector-borne disease, antibiotic resistance, and evolution in a changing environment. Heuristic and analytic methods developed under this proposal can be applied to genomic data in humans to aid in identifying disease causing loci that have become prevalent in humans as we have colonized the world and been exposed to novel environments.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM100366-06
Application #
9357625
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Janes, Daniel E
Project Start
2012-05-15
Project End
2020-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
6
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Rajpurohit, Subhash; Gefen, Eran; Bergland, Alan O et al. (2018) Spatiotemporal dynamics and genome-wide association genome-wide association analysis of desiccation tolerance in Drosophila melanogaster. Mol Ecol 27:3525-3540
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Rajpurohit, S; Hanus, R; Vrkoslav, V et al. (2017) Adaptive dynamics of cuticular hydrocarbons in Drosophila. J Evol Biol 30:66-80
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Assaf, Zoe June; Tilk, Susanne; Park, Jane et al. (2017) Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations. Genome Res 27:1988-2000
Rajpurohit, Subhash; Zhao, Xiaqing; Schmidt, Paul S (2017) A resource on latitudinal and altitudinal clines of ecologically relevant phenotypes of the Indian Drosophila. Sci Data 4:170066
Wittmann, Meike J; Bergland, Alan O; Feldman, Marcus W et al. (2017) Seasonally fluctuating selection can maintain polymorphism at many loci via segregation lift. Proc Natl Acad Sci U S A 114:E9932-E9941

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