Animals, including humans, contain a small number of cells in their gonads called germline stem cells (GSCs). These cells are essential for making sperm or eggs throughout the lifetime of the animal. The decision for a dividing stem cell to renew as a stem cell or to differentiate, and the regulation of early divisions during GSC are some of the most critical decisions in development. Studies in the fruit fly, Drosophila melanogaster, have identified many of the key genes involved in the cellular signaling for GSC maintenance and differentiation. Several of the key GSC regulatory genes are rapidly evolving under adaptive evolution in two closely related species of Drosophila (D. melanogaster and its sibling species D. simulans) but not in several additional closely related species. The key ?switch? gene for GSC differentiation, bag of marbles (bam) has accumulated a highly significant excess of amino-acid changes between these two closely related species (13%). This proposal focuses on identifying the functional consequences of these changes and gaining insight into possible evolutionary forces driving these changes, including interactions with the endosymbiotic bacteria Wolbachia. This knowledge is essential for understanding how GSCs are regulated during normal development and how their misregulation due to mutation and interaction with germline parasites can lead to infertility, germline cancers, and reproductive isolation. Our proposed studies provide a framework with which to test the functional consequences and evolutionary forces driving these evolutionary changes in genes controlling stem cell fate decisions in Drosophila as well as in other organisms, including humans.
Germline stem cells (GSCs) are arguably the most fundamental cell type required for animal reproduction because these cells both maintain the germline throughout the animal's life, and produce the cells that go on to form either sperm or eggs. Remarkably, several key GSC regulatory genes are under strong natural selection to change at the protein sequence level between species of Drosophila. Our proposed study is aimed at identifying the functional consequences and correlated evolutionary pressures associated with the rapid protein evolution of bag of marbles, the key switch gene for GSC differentiation.
|Raghavan, Vandana; Bui, Duyen T; Al-Sweel, Najla et al. (2018) Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Baker's Yeast. Genetics 210:1253-1266|
|Bui, Duyen T; Friedrich, Anne; Al-Sweel, Najla et al. (2017) Mismatch Repair Incompatibilities in Diverse Yeast Populations. Genetics 205:1459-1471|
|Choi, Jae Young; Aquadro, Charles F (2016) Recent and Long-Term Selection Across Synonymous Sites in Drosophila ananassae. J Mol Evol 83:50-60|
|Choi, Jae Young; Bubnell, Jaclyn E; Aquadro, Charles F (2015) Population Genomics of Infectious and Integrated Wolbachia pipientis Genomes in Drosophila ananassae. Genome Biol Evol 7:2362-82|
|Bui, Duyen T; Dine, Elliot; Anderson, James B et al. (2015) A Genetic Incompatibility Accelerates Adaptation in Yeast. PLoS Genet 11:e1005407|
|Flores, Heather A; DuMont, Vanessa L Bauer; Fatoo, Aalya et al. (2015) Adaptive evolution of genes involved in the regulation of germline stem cells in Drosophila melanogaster and D. simulans. G3 (Bethesda) 5:583-92|
|Choi, Jae Young; Aquadro, Charles F (2015) Molecular Evolution of Drosophila Germline Stem Cell and Neural Stem Cell Regulating Genes. Genome Biol Evol 7:3097-114|
|Flores, Heather A; Bubnell, Jaclyn E; Aquadro, Charles F et al. (2015) The Drosophila bag of marbles Gene Interacts Genetically with Wolbachia and Shows Female-Specific Effects of Divergence. PLoS Genet 11:e1005453|
|Zaborske, John M; DuMont, Vanessa L Bauer; Wallace, Edward W J et al. (2014) A nutrient-driven tRNA modification alters translational fidelity and genome-wide protein coding across an animal genus. PLoS Biol 12:e1002015|
|Choi, Jae Young; Aquadro, Charles F (2014) The coevolutionary period of Wolbachia pipientis infecting Drosophila ananassae and its impact on the evolution of the host germline stem cell regulating genes. Mol Biol Evol 31:2457-71|
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