Is most complex trait variation caused by a few common alleles, or is it largely due to the aggregate contributions of many rare variants? How large are per-locus allelic effects on quantitative traits? Is effect size correlated with allele frequency across loci? These are questions of import throughout biology. Mutation- selection balance predicts that polymorphic loci will have rare alleles while balancing selection models predict intermediate allele frequencies. The respective contributions of these evolutionary mechanisms determines the relevance of standing variation to adaptive evolution and the extent to which quantitative trait evolution is limited by mutation as opposed to selection. In human health, the so-called common disease/common variant hypothesis is a statement on these conditions and its validity has clear clinical implications. The proposed studies advance ongoing experiments using the model plant Mimulus guttatus to provide a rigorous exploration of the genetic and ecological factors that maintain genetic variation in natural populations.
The aims are to determine sequence-level determinants of variation in fitness-related traits. This research involves a combination of classical and modern genetics, molecular biology, statistical modeling, and field experimentation. The research should determine not only whether natural selection maintains genetic variation in ecologically important traits, but will begin to elucidate the particular selective agents that are involved.
The third aim also develops a novel procedure for population mapping of quantitative trait loci that is potentially applicable to a broad range of organisms. The proposed studies will train undergraduates, doctoral students, and postdoctoral researchers in each of the four years of the project.

Public Health Relevance

The proposed studies directly investigate the genetic architecture of complex traits. Most chronic human diseases are complex traits and the dissection of genetic causes is a major research focus of the National Institutes of Health. Our experiments on the model plant Mimulus guttatus provide relevant results and 'proof-of-concept'of genetic methods for future health-related research.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Genetic Variation and Evolution Study Section (GVE)
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Eckstrand, Irene A
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University of Kansas Lawrence
Schools of Arts and Sciences
United States
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Holeski, Liza M; Monnahan, Patrick; Koseva, Boryana et al. (2014) A high-resolution genetic map of yellow monkeyflower identifies chemical defense QTLs and recombination rate variation. G3 (Bethesda) 4:813-21
Flagel, Lex E; Willis, John H; Vision, Todd J (2014) The standing pool of genomic structural variation in a natural population of Mimulus guttatus. Genome Biol Evol 6:53-64
Delph, Lynda F; Kelly, John K (2014) On the importance of balancing selection in plants. New Phytol 201:45-56
Fishman, L; Willis, J H; Wu, C A et al. (2014) Comparative linkage maps suggest that fission, not polyploidy, underlies near-doubling of chromosome number within monkeyflowers (Mimulus; Phrymaceae). Heredity (Edinb) 112:562-8
Kelly, John K; Koseva, Boryana; Mojica, Julius P (2013) The genomic signal of partial sweeps in Mimulus guttatus. Genome Biol Evol 5:1457-69
Anderson, Jill T; Willis, John H; Mitchell-Olds, Thomas (2011) Evolutionary genetics of plant adaptation. Trends Genet 27:258-66
Scoville, Alison G; Lee, Young Wha; Willis, John H et al. (2011) Explaining the heritability of an ecologically significant trait in terms of individual quantitative trait loci. Biol Lett 7:896-8
Magwene, Paul M; Willis, John H; Kelly, John K (2011) The statistics of bulk segregant analysis using next generation sequencing. PLoS Comput Biol 7:e1002255
Roels, Sarah A Bodbyl; Kelly, John K (2011) Rapid evolution caused by pollinator loss in Mimulus guttatus. Evolution 65:2541-52
Kelly, John K; Mojica, Julius P (2011) Interactions among flower-size QTL of Mimulus guttatus are abundant but highly variable in nature. Genetics 189:1461-71

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