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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM073990-06
Application #
8404038
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
2006-05-01
Project End
2015-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
6
Fiscal Year
2013
Total Cost
$351,451
Indirect Cost
$74,958
Name
University of Kansas Lawrence
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
076248616
City
Lawrence
State
KS
Country
United States
Zip Code
66045
Lee, Young Wha; Fishman, Lila; Kelly, John K et al. (2016) A Segregating Inversion Generates Fitness Variation in Yellow Monkeyflower (Mimulus guttatus). Genetics 202:1473-84
Puzey, Joshua R; Willis, John H; Kelly, John K (2016) Population structure and local selection yield high genomic variation in Mimulus guttatus. Mol Ecol :
Colicchio, Jack M; Miura, Fumihito; Kelly, John K et al. (2015) DNA methylation and gene expression in Mimulus guttatus. BMC Genomics 16:507
Monnahan, Patrick J; Kelly, John K (2015) Naturally segregating loci exhibit epistasis for fitness. Biol Lett 11:
Fishman, Lila; Kelly, John K (2015) Centromere-associated meiotic drive and female fitness variation in Mimulus. Evolution 69:1208-18
Monnahan, Patrick J; Colicchio, Jack; Kelly, John K (2015) A genomic selection component analysis characterizes migration-selection balance. Evolution 69:1713-27
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
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
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
Delph, Lynda F; Kelly, John K (2014) On the importance of balancing selection in plants. New Phytol 201:45-56

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