What is the relative importance of evolutionary factors that maintain genetic variation within populations and species? Two evolutionary mechanisms contribute to trait variation in populations, although their relative importance remains unclear. Recurring deleterious variants provide a continual influx of harmful alleles which are gradually removed by purifying selection. In addition, balancing selection can maintain polymorphisms due to advantageous phenotypes. Understanding the importance of these alternatives has important implications for the genetics of human health and variation in the organisms around us. These questions will be addressed using a cloned quantitative trait locus (QTL) within a well-characterized pathway in the model plant Boechera stricta. This system provides known molecular mechanisms, and fitness can be measured in undisturbed populations and undisturbed habitats, enabling tests of evolutionary hypotheses in historically relevant environments. These analyses combine genetic variation in biochemical and regulatory function, measurements of resistance traits and fitness in nature, and the geography and history of functional alleles. Such experiments to understand the evolutionary significance of complex trait variation must confront the limitations of the QTL program: the large-effect alleles that can be discovered may be unrepresentative of the genes that matter for evolution. This proposed research moves beyond this limitation. Beginning with a large-effect polymorphism that influences defensive chemistry and individual fitness in nature, multiple, small-effect functional allelic differences have been identified. The proposed experiments will quantify precisely the allelic effects on defensive chemistry and gene expression, and will measure the consequences of this variation in nature in order to understand variation of natural selection in space and time. These approaches can elucidate the relative importance of evolutionary factors that maintain genetic variation for ecologically important traits.

Public Health Relevance

These proposed experiments examine genetic variation for complex traits, which are fundamental for human health and for organisms in their environments. Analyses will examine the evolutionary forces that influence genetic variation in populations. This research is focused on genes that synthesize glucosinolates, which are present in human diets and have well documented effects on resistance to cancer.

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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Duke University
Schools of Arts and Sciences
United States
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