title: Whole-Genome Resequencing of Experimental Populations Reveals Polygenic Basis of Egg-Size Variation in Drosophila melanogaster.
abstract: Complete genome resequencing of populations holds great promise in deconstructing complex polygenic traits to elucidate molecular and developmental mechanisms of adaptation. Egg size is a classic adaptive trait in insects, birds, and other taxa, but its highly polygenic architecture has prevented high-resolution genetic analysis. We used replicated experimental evolution in Drosophila melanogaster and whole-genome sequencing to identify consistent signatures of polygenic egg-size adaptation. A generalized linear-mixed model revealed reproducible allele frequency differences between replicated experimental populations selected for large and small egg volumes at approximately 4,000 single nucleotide polymorphisms (SNPs). Several hundred distinct genomic regions contain clusters of these SNPs and have lower heterozygosity than the genomic background, consistent with selection acting on polymorphisms in these regions. These SNPs are also enriched among genes expressed in Drosophila ovaries and many of these genes have well-defined functions in Drosophila oogenesis. Additional genes regulating egg development, growth, and cell size show evidence of directional selection as genes regulating these biological processes are enriched for highly differentiated SNPs. Genetic crosses performed with a subset of candidate genes demonstrated that these genes influence egg size, at least in the large genetic background. These findings confirm the highly polygenic architecture of this adaptive trait, and suggest the involvement of many novel candidate genes in regulating egg size.
authors.affiliation: Institute for Genomics and Systems Biology, The University of Chicago Department of Human Genetics, The University of Chicago Department of Ecology and Evolution, The University of Chicago nepaliaashish@gmail.com mkre@uchicago.edu.
authors.forename: Aashish R
authors.initials: AR
authors.lastname: Jha
authors.affiliation: Department of Biology, Augustana College, Sioux Falls, SD.
authors.forename: Cecelia M
authors.initials: CM
authors.lastname: Miles
authors.affiliation: Department of Biology, Augustana College, Sioux Falls, SD.
authors.forename: Nodia R
authors.initials: NR
authors.lastname: Lippert
authors.affiliation: Institute for Genomics and Systems Biology, The University of Chicago Department of Genetics, Perelman School of Medicine, University of Pennsylvania.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Brown
authors.affiliation: Institute for Genomics and Systems Biology, The University of Chicago Department of Human Genetics, The University of Chicago Department of Ecology and Evolution, The University of Chicago Committee on Genetics, Genomics & Systems Biology, The University of Chicago.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: White
authors.affiliation: Institute for Genomics and Systems Biology, The University of Chicago Department of Ecology and Evolution, The University of Chicago Committee on Genetics, Genomics & Systems Biology, The University of Chicago nepaliaashish@gmail.com mkre@uchicago.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Kreitman
mesh_terms: D000818:Animals; D048429:Cell Size; D003433:Crosses, Genetic; D019020:Directed Molecular Evolution; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency / Q000235:genetics; D063990:Gene Ontology; D056726:Genetic Association Studies; D014644:Genetic Variation; D049750:Genome, Insect; D008297:Male; D020412:Multifactorial Inheritance / Q000235:genetics*; D010063:Ovum / Q000166:cytology*; D010641:Phenotype; D017422:Sequence Analysis, DNA / Q000379:methods*
keywords: adaptation; complex traits; egg size; evolution; experimental evolution; polygenic adaptation; pooled sequencing