Recent studies suggest that positive selection is driving rapid divergence of genes involved in reproductive isolation between species. Detailed characterization of reproductive isolation genes will therefore contribute to our knowledge both of species-specific traits and adaptations and of the speciation process itself. We have) recently shown that the gene Hmr causes Fl hybrid lethality between Drosophila melanogaster and its sibling; species, and suggested that a second gene, Lhr, is also involved in this lethality.
In Aim 1 of this proposal we propose to clone the Lhr gene in order to test the hypothesis that hybrid lethality is caused by the interaction of the D. melanogaster Hmr gene and the sibling-species Lhr gene. We will attempt to reconstitute the interspecific incompatibility entirely within /). melanogaster strains using transgenic constructs. We will also create a loss-of-function mutation in Lhr in D. melanogaster in order to understand the function of Lhr within species.
Aim 2 will explore the relationship between the molecular evolution and the functional properties ct Hmr with respect to its intraspecific and hybrid functions. We will do developmental analyses of Hmr loss of- function mutants and of interspecific hybrids, use molecular evolutionary and population genetic techniques to identify regions and codons of Hmr that may be diverging under selection, and then use transgenic assays to test the functional consequences of hypotheses derived from these evolutionary analyses. We will also investigate whether Lhr has diverged under selection between D. melanogaster and its sibling species.
In Aim 3 a genetic screen will be done in D. melanogaster to identify new genes that interact with Hmr and Lhr to cause hybrid lethality. The forthcoming whole-genome sequence from the sibling species D. simulans as well as several other Drosophila species will greatly enhance both the technical feasibility and the potential impact of this proposal as a model for testing functional consequences of sequence divergence.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM074737-04
Application #
7490581
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
2005-09-01
Project End
2009-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
4
Fiscal Year
2008
Total Cost
$240,375
Indirect Cost
Name
Cornell University
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Wei, Kevin H-C; Lower, Sarah E; Caldas, Ian V et al. (2018) Variable Rates of Simple Satellite Gains across the Drosophila Phylogeny. Mol Biol Evol 35:925-941
Ulmschneider, Martin B; Ulmschneider, Jakob P; Freites, J Alfredo et al. (2017) Transmembrane helices containing a charged arginine are thermodynamically stable. Eur Biophys J 46:627-637
Blum, Jacob A; Bonaccorsi, Silvia; Marzullo, Marta et al. (2017) The Hybrid Incompatibility Genes Lhr and Hmr Are Required for Sister Chromatid Detachment During Anaphase but Not for Centromere Function. Genetics 207:1457-1472
Wei, Kevin H-C; Reddy, Hemakumar M; Rathnam, Chandramouli et al. (2017) A Pooled Sequencing Approach Identifies a Candidate Meiotic Driver in Drosophila. Genetics 206:451-465
Dion-Côté, Anne-Marie; Barbash, Daniel A (2017) Beyond speciation genes: an overview of genome stability in evolution and speciation. Curr Opin Genet Dev 47:17-23
Wei, Kevin H-C; Barbash, Daniel A (2015) Never settling down: frequent changes in sex chromosomes. PLoS Biol 13:e1002077
Gilliland, William D; Colwell, Eileen M; Osiecki, David M et al. (2015) Normal segregation of a foreign-species chromosome during Drosophila female meiosis despite extensive heterochromatin divergence. Genetics 199:73-83
Wei, Kevin H-C; Grenier, Jennifer K; Barbash, Daniel A et al. (2014) Correlated variation and population differentiation in satellite DNA abundance among lines of Drosophila melanogaster. Proc Natl Acad Sci U S A 111:18793-8
Cuykendall, Tawny N; Satyaki, P; Ji, Shuqing et al. (2014) A screen for F1 hybrid male rescue reveals no major-effect hybrid lethality loci in the Drosophila melanogaster autosomal genome. G3 (Bethesda) 4:2451-60
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

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