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

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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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Genetic Variation and Evolution Study Section (GVE)
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Eckstrand, Irene A
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Princeton University
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Rogers, Rebekah L; Cridland, Julie M; Shao, Ling et al. (2015) Tandem Duplications and the Limits of Natural Selection in Drosophila yakuba and Drosophila simulans. PLoS One 10:e0132184
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
Rogers, Rebekah L; Shao, Ling; Sanjak, Jaleal S et al. (2014) Revised annotations, sex-biased expression, and lineage-specific genes in the Drosophila melanogaster group. G3 (Bethesda) 4:2345-51
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
Zhen, Ying; Aardema, Matthew L; Medina, Edgar M et al. (2012) Parallel molecular evolution in an herbivore community. Science 337:1634-7
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

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