New species form when diverging populations become reproductively isolated. One cause of this isolation is hybrid incompatibility, the sterility and lethality of interspecific hybrids. This proposal investigates two previously identified genes that interact to cause lethality in hybrids between the fruit fly species Drosophila melanogaster and D. simulans. Sequence analysis of both genes shows that they have evolved under adaptive evolution, a pattern also observed with other hybrid incompatibility genes. Identifying the specific selective forces causing this pattern of molecular evolution will therefore help elucidate the biological causes of speciation. This proposal is based on the recent discovery that these Drosophila hybrid incompatibility genes are required to repress transposable elements, selfish DNAs that can mobilize, reach high copy number, and cause significant damage to eukaryotic genomes. A range of genetic and molecular assays are proposed here to identify how these genes function in repressing transposable elements, including profiling the genome-wide pattern of transposition in mutant lines. Other phenotypic assays will investigate how these genes affect fertility and meiotic performance within their own host species. Attention will then turn to an integrated effort to determine how sequence divergence and adaptive evolution between species has altered specific functions of these genes. Transposable elements are a major cause of spontaneous mutation and DNA damage in eukaryotes including humans. The proposed studies will provide a high resolution view of how transposable element load contributes to host gene evolution and reproductive isolation between species.

Public Health Relevance

The genomes of humans and other animals are littered with parasitic DNAs that can cause havoc when they become unregulated. Many animal genes are dedicated to regulating these parasitic DNAs, and as these genes change they can contribute to the formation of new species. This process can be studied in great detail using experimental genetic approaches in fruit flies.

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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Cornell University
Schools of Arts and Sciences
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Ferree, Patrick M; Gomez, Karina; Rominger, Peter et al. (2014) Heterochromatin position effects on circularized sex chromosomes cause filicidal embryonic lethality in Drosophila melanogaster. Genetics 196:1001-5
Satyaki, P R V; Cuykendall, Tawny N; Wei, Kevin H-C et al. (2014) The Hmr and Lhr hybrid incompatibility genes suppress a broad range of heterochromatic repeats. PLoS Genet 10:e1004240
Wei, Kevin H-C; Clark, Andrew G; Barbash, Daniel A (2014) Limited gene misregulation is exacerbated by allele-specific upregulation in lethal hybrids between Drosophila melanogaster and Drosophila simulans. Mol Biol Evol 31:1767-78
Andersson, Magnus; Ulmschneider, Jakob P; Ulmschneider, Martin B et al. (2013) Conformational states of melittin at a bilayer interface. Biophys J 104:L12-4
Kelleher, Erin S; Barbash, Daniel A (2013) Analysis of piRNA-mediated silencing of active TEs in Drosophila melanogaster suggests limits on the evolution of host genome defense. Mol Biol Evol 30:1816-29
Maheshwari, Shamoni; Barbash, Daniel A (2012) Cis-by-Trans regulatory divergence causes the asymmetric lethal effects of an ancestral hybrid incompatibility gene. PLoS Genet 8:e1002597
Mihailescu, Mihaela; Vaswani, Rishi G; Jardon-Valadez, Eduardo et al. (2011) Acyl-chain methyl distributions of liquid-ordered and -disordered membranes. Biophys J 100:1455-62
Maheshwari, Shamoni; Barbash, Daniel A (2011) The genetics of hybrid incompatibilities. Annu Rev Genet 45:331-55
Ulmschneider, Jakob P; Andersson, Magnus; Ulmschneider, Martin B (2011) Determining peptide partitioning properties via computer simulation. J Membr Biol 239:15-26
Barbash, Daniel A (2010) Ninety years of Drosophila melanogaster hybrids. Genetics 186:1-8

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