A growing body of evidence supports the view that regulatory evolution - the evolution of where and when a gene is expressed - is the primary genetic mechanism behind the modular organization, functional diversification, and origin of novel traits in higher organisms. Most elements regulating gene expression in eukaryotic genomes reside in noncoding DNA (i.e. DNA that does not encode protein). Recent studies suggest that much of the noncoding portion of the Drosophila melanogaster genome is evolutionarily constrained, implying that these regions are important for an organism

Public Health Relevance

Changes in genetic regulation contribute to adaptations in natural populations and influence susceptibility to human diseases (Gilad et al. 2008;Gobbi et al. 2006). Despite their potential phenotypic importance, the selective pressures acting on regulatory processes and gene expression levels in particular are largely unknown. Our research combines computational and experimental approaches to study how natural selection acts on genetic variation underlying both beneficial and detrimental functional differences in gene expression. This work will significantly improve our understanding of biology of human diseases caused by the misexpression of genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM083228-05
Application #
8514007
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
2009-09-01
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$283,176
Indirect Cost
$91,111
Name
Princeton University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Rogers, Rebekah L; Cridland, Julie M; Shao, Ling et al. (2014) Landscape of standing variation for tandem duplications in Drosophila yakuba and Drosophila simulans. Mol Biol Evol 31:1750-66
Simons, Yuval B; Turchin, Michael C; Pritchard, Jonathan K et al. (2014) The deleterious mutation load is insensitive to recent population history. Nat Genet 46:220-4
Hu, Tina T; Eisen, Michael B; Thornton, Kevin R et al. (2013) A second-generation assembly of the Drosophila simulans genome provides new insights into patterns of lineage-specific divergence. Genome Res 23:89-98
Benger, Etam; Sella, Guy (2013) Modeling the effect of changing selective pressures on polymorphism and divergence. Theor Popul Biol 85:73-85
Slotte, Tanja; Hazzouri, Khaled M; Stern, David et al. (2012) Genetic architecture and adaptive significance of the selfing syndrome in Capsella. Evolution 66:1360-74
Garrigan, Daniel; Kingan, Sarah B; Geneva, Anthony J et al. (2012) Genome sequencing reveals complex speciation in the Drosophila simulans clade. Genome Res 22:1499-511
Zhen, Ying; Andolfatto, Peter (2012) Methods to detect selection on noncoding DNA. Methods Mol Biol 856:141-59
Hernandez, Ryan D; Kelley, Joanna L; Elyashiv, Eyal et al. (2011) Classic selective sweeps were rare in recent human evolution. Science 331:920-4
Sattath, Shmuel; Elyashiv, Eyal; Kolodny, Oren et al. (2011) Pervasive adaptive protein evolution apparent in diversity patterns around amino acid substitutions in Drosophila simulans. PLoS Genet 7:e1001302
Wilson, Daniel J; Hernandez, Ryan D; Andolfatto, Peter et al. (2011) A population genetics-phylogenetics approach to inferring natural selection in coding sequences. PLoS Genet 7:e1002395

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