One of the most influential findings of the last 20 years in molecular evolutionary studies has been that recombination rate is frequently correlated with nucleotide sequence diversity within a species. In Drosophila species, this relationship has been attributed to natural selection, while neutral causes have been attributed as primary contributors to this association in humans. However, the relationship of recombination to diversity has not been observed in all species examined, and conflicting reports also exist on whether recombination rate is associated with interspecies sequence divergence or codon usage bias. If there is fine-scale heterogeneity in recombination rate across a genome, the conflicting conclusions could result from differences in the scale with which recombination is measured. Additionally, interpreting the evolutionary causes of these associations to recombination rate can be facilitated by evaluations at multiple scales. This proposal takes a collaborative and interdisciplinary approach to tackling these oft- cited relationships. Building upon a successful preliminary study, the investigators will construct very high resolution linkage maps using the species Drosophila pseudoobscura, and correlate local recombination rates to various sequence motifs. They will also generate multiple whole-genome sequence assemblies of this species from which to carefully examine patterns of nucleotide diversity at an unprecedented scale. Finally, extensive modeling is proposed to examine possible effects of background selection and selective sweeps to infer conditions under which they can operate to produce the observed associations between recombination rate and diversity, divergence, or codon bias. The investigators have extensive experience with all of the proposed work, as illustrated by the preliminary results reported.

Public Health Relevance

Drosophila fruit flies and humans likely share many metabolic housekeeping genes and thus could experience similar absolute selection coefficients. Because humans have a much smaller population size, we accumulate many detrimental mutations that would be eliminated in Drosophila, so quantifying the contributions of such classes of mutations to genome evolution using a model system could potentially inform the rate of accumulation of hereditary human diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM086445-04
Application #
8246526
Study Section
Special Emphasis Panel (ZRG1-GGG-C (62))
Program Officer
Eckstrand, Irene A
Project Start
2009-04-06
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2012
Total Cost
$267,560
Indirect Cost
$56,642
Name
Duke University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Gredler, Jennifer N; Hish, Alexander J; Noor, Mohamed A F (2015) Temporal Stability of Molecular Diversity Measures in Natural Populations of Drosophila pseudoobscura and Drosophila persimilis. J Hered 106:407-11
Hoehn, Kenneth B; Noor, Mohamed A F (2014) How big is your Y? A genome sequence-based estimate of the size of the male-specific region in Megaselia scalaris. G3 (Bethesda) 5:45-8
Kliman, Richard M (2014) Evidence that natural selection on codon usage in Drosophila pseudoobscura varies across codons. G3 (Bethesda) 4:681-92
Manzano-Winkler, Brenda; McGaugh, Suzanne E; Noor, Mohamed A F (2013) How hot are drosophila hotspots? examining recombination rate variation and associations with nucleotide diversity, divergence, and maternal age in Drosophila pseudoobscura. PLoS One 8:e71582
McDermott, S R; Noor, M A F (2012) Mapping of within-species segregation distortion in Drosophila persimilis and hybrid sterility between D.ýýpersimilis and D.ýýpseudoobscura. J Evol Biol 25:2023-32
McGaugh, Suzanne E; Heil, Caiti S S; Manzano-Winkler, Brenda et al. (2012) Recombination modulates how selection affects linked sites in Drosophila. PLoS Biol 10:e1001422
Hoehn, Kenneth B; McGaugh, Suzanne E; Noor, Mohamed A F (2012) Effects of premature termination codon polymorphisms in the Drosophila pseudoobscura subclade. J Mol Evol 75:141-50
Graham, Allie M; Merrill, Jennifer D; McGaugh, Suzanne E et al. (2012) Geographic selection in the small heat shock gene complex differentiating populations of Drosophila pseudoobscura. J Hered 103:400-7
Heil, Caiti S S; Noor, Mohamed A F (2012) Zinc finger binding motifs do not explain recombination rate variation within or between species of Drosophila. PLoS One 7:e45055
Heil, Caiti S S; Hunter, Mika J; Noor, Juliet Kf et al. (2012) Witnessing Phenotypic and Molecular Evolution in the Fruit Fly. Evolution (N Y) 5:629-634

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