The goal of this project is to identify the nucleotide changes that have led to phenotypic differences between closely related Drosophila species. The larger goal is to determine whether these evolved changes reflect a special set of all possible mutations. There are three specific aims for this proposal. First, we will survey three previously identified enhancer regions of the shavenbaby/ovo gene for all transcription factor binding sites that can be detected in vitro. This analysis will leverage the fact that all three enhancers have evolved new functions in D. sechellia, presumably through the loss or gain of transcription factor binding sites. This survey will provide the foundation for detailed study of binding sites that have evolved new functions. In particular, we will test whether these sites are required for gene function in D. melanogaster and we will further test whether altering them to a D. sechellia sequence is sufficient to alter their function in the manner in which svb function has evolved. We will then perform a population genetic analysis of the conserved and evolved transcription factor binding sites to test whether the evolving sites have evolved by natural selection. Second, we will continue development of a novel method for ultra high-resolution mapping of evolved differences between D. simulans, D. sechellia and D. mauritiana. This new method extends traditional meiotic mapping approaches by employing genetic markers that flank an evolved region to allow automated identification of individuals with informative recombination events. This approach promises to provide a transformative technology for studying the evolution of a large and diverse set of phenotypic differences, especially so-called quantitative traits that are controlled by multiple genes. Relevance: Differences between the response of individuals to disease and drug treatment are caused in part by genetic variation. In addition, the traits that make us uniquely human evolved in large part through changes in gene regulation, rather than through the evolution of new genes. This project involves detailed study of the evolution of a new pattern of gene regulation in a species of Drosophila. This detailed analysis of gene regulation promises to provide new insights into how gene regulation functions and evolves in natural species to cause possibly adaptive changes in morphology.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM063622-09
Application #
7851189
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
2001-08-01
Project End
2011-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
9
Fiscal Year
2010
Total Cost
$262,244
Indirect Cost
Name
Princeton University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Frankel, Nicolas; Wang, Shu; Stern, David L (2012) Conserved regulatory architecture underlies parallel genetic changes and convergent phenotypic evolution. Proc Natl Acad Sci U S A 109:20975-9
Frankel, Nicolás; Erezyilmaz, Deniz F; McGregor, Alistair P et al. (2011) Morphological evolution caused by many subtle-effect substitutions in regulatory DNA. Nature 474:598-603
Andolfatto, Peter; Davison, Dan; Erezyilmaz, Deniz et al. (2011) Multiplexed shotgun genotyping for rapid and efficient genetic mapping. Genome Res 21:610-7
Frankel, Nicolas; Davis, Gregory K; Vargas, Diego et al. (2010) Phenotypic robustness conferred by apparently redundant transcriptional enhancers. Nature 466:490-3
Erezyilmaz, Deniz F; Kelstrup, Hans C; Riddiford, Lynn M (2009) The nuclear receptor E75A has a novel pair-rule-like function in patterning the milkweed bug, Oncopeltus fasciatus. Dev Biol 334:300-10
Rebeiz, Mark; Ramos-Womack, Margarita; Jeong, Sangyun et al. (2009) Evolution of the tan locus contributed to pigment loss in Drosophila santomea: a response to Matute et al. Cell 139:1189-96
Brisson, Jennifer A; Nuzhdin, Sergey V; Stern, David L (2009) Similar patterns of linkage disequilibrium and nucleotide diversity in native and introduced populations of the pea aphid, Acyrthosiphon pisum. BMC Genet 10:22
Stern, David L; Orgogozo, Virginie (2008) The loci of evolution: how predictable is genetic evolution? Evolution 62:2155-77
Rockman, Matthew V; Stern, David L (2008) Tinker where the tinkering's good. Trends Genet 24:317-9
Stern, David L (2008) Aphids. Curr Biol 18:R504-5

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