Our long term goal is to understand how natural genetic variation generates morphological variation. We pursue this goal by combining approaches from developmental genetics and evolutionary biology. Recent work from our lab and others has demonstrated that alterations in gene regulation are likely to be the predominant mode of molecular change underlying morphological evolution. However, we currently have a limited understanding of the structure and function of the genomic regions that regulate gene expression. In addition, several studies have demonstrated that regulatory regions can evolve dramatically different DNA sequences while retaining conserved function. In contrast to studies of genes with conserved patterns of gene expression, almost nothing is known at the molecular level about the alterations in gene function that lead to morphological evolution. Our work is focused on identifying and characterising the DNA changes that are responsible for morphological evolution between closely related species. We have already identified some of the genes that have evolved between closely related Drosophila species to alter the patterning of fine hairs (trichomes) on the larvae and adult. We will perform a detailed investigation of the evolution of the regulatory regions of these genes by combining functional studies and phylogenetic comparisons of DNA sequence variation. Although gene regulatory regions encode much of the logic of development, it is not yet possible to read this logic directly from genomic data. An evolutionary approach to understanding the function of these gene regions is likely to provide important insights into the logic of gene regulatory regions and assist in the interpretation of comparative genomics data.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Genetics Study Section (GEN)
Program Officer
Eckstrand, Irene A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Princeton University
Schools of Arts and Sciences
United States
Zip Code
Frankel, Nicolás; 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

Showing the most recent 10 out of 18 publications