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Adaptive Protein Evolution of the Drosophila Germline Stem Cell Gene Bag of Marbles

果蝇种系干细胞基因袋大理石的适应性蛋白质进化

基本信息

批准号：
10298579
负责人：
CHARLES F AQUADRO
金额：
$ 33.76万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10298579
关键词：
Address Amino Acid Sequence Amino Acid Substitution Amino Acids Animals Automobile Driving Bacteria CRISPR/Cas technology Cell Communication Cell Differentiation process Cell Maintenance Cells Characteristics Computer Models Conflict (Psychology)Culicidae Development Developmental Process Diptera Drosophila genus Drosophila melanogaster Evolution Female Fertility Fertility Disorders Fossils Funding Gametogenesis Gene Expression Genes Genetic Genetic Transcription Genome Germ Cells Hand Infection Infertility Insecta Lead Learning Life Malignant Neoplasms Marble Modeling Molecular Mutation Natural Selections Nature Parasites Pattern Process Proteins Regulation Regulator Genes Reproduction Role Shapes Signal Transduction Surveys Switch Genes Testing Time Variant Virus Wolbachia cell type comparative driving force egg endosymbiont female fertility fly germline stem cells human pathogen improved innovation insight loss of function male mutant novel null mutation pressure reference genome reproductive self-renewal sperm cell stem cell differentiation stem cell division stem cell function stem cell genes stem cells symbiont tool transcriptome sequencing

项目摘要

PROJECT SUMMARY Animals contain a small number of germline stem cells (GSCs) that are essential for making sperm or eggs. The decision for a dividing stem cell to renew itself or to differentiate, and the regulation of early GSC divisions are some of the most critical processes 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. We have shown that the gene bag of marbles (bam), the key “switch” for GSC differentiation, is adaptively evolving with a dramatic excess of amino acid substitutions in D. melanogaster, D. simulans, D. yakuba but not in six other related species. During our current funding period we have generated new bam null mutations in sequenced genomes of D. melanogaster, D. simulans, D. yakuba, D. teissieri, and D. ananassae to test for conservation of function. These have allowed us to demonstrate that surprisingly unlike in D. melanogaster, bam is not required for female GSC differentiation in D. teissieri nor is it required for male GSC differentiation in D. teissieri and D. ananassae. We have shown that infection with different strains of the intracellular endosymbiont Wolbachia pipientis vary in their degree of rescue of the fertility defects characteristic of the bam hypomorph. This proposal focuses on identifying the functional and evolutionary consequences of observed sequence diversification at bam and discriminating between the hypothesis that bam’s role in GSC function has been selected for new functions, vs the hypothesis that interactions between bam and W. pipientis has been the evolutionary force driving changes at bam. This includes generating and analyzing novel bam hypomorphs in D. melanogaster and D. simulans, and testing interactions of these new hypomorphs with intra and interspecific Wolbachia strains. We will carry out RNA-seq studies of the bam rescue by W. pipientis. We are developing a computational model to generate experimentally testable predictions of sequence diversification under several mechanisms of interaction between W. pipientis and GSC genes. Finally, we will functionally evaluate evolutionary diversification of the bam protein sequence between D. melanogaster and D. simulans, and the loss of the requirement for bam for female and male gametogenesis and fertility in D. teissieri compared to its close relative D. yakuba. What we learn will contribute significantly to our understanding of how GSCs are regulated during development in diverse species, how such critical developmental functions can evolve, and how their mis-regulation due to mutation and interaction with germline parasites can lead to infertility, germline cancers, and reproductive isolation.

项目总结