Adaptive Protein Evolution of the Drosophila Germline Stem Cell Gene Bag of Marbles
Adaptive Protein Evolution of the Drosophila Germline Stem Cell Gene Bag of Marbles
批准号:
10618937
负责人:
CHARLES F AQUADRO
金额:
$33.95万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
未结题
起止时间:
2011-08-01 至 2025-05-31
关键词:
AddressAgeAmino Acid SequenceAmino Acid SubstitutionAmino AcidsAnimalsAutomobile DrivingBacteriaCRISPR/Cas technologyCell CommunicationCell Differentiation processCell MaintenanceCellsCharacteristicsComputer ModelsConflict (Psychology)CulicidaeDevelopmentDevelopmental ProcessDipteraDrosophila genusDrosophila melanogasterEvolutionFemaleFertilityFertility DisordersFossilsFundingGametogenesisGene ExpressionGenesGeneticGenetic TranscriptionGenomeGerm CellsHandInfectionInfertilityInsectaLearningLifeMalignant NeoplasmsMarbleModelingMolecularMutationNatural SelectionsNatureParasitesPatternProcessProteinsRegulationRegulator GenesReproductionRoleShapesSignal TransductionSurveysSwitch GenesTestingTimeVariantVirusWolbachiabarrier to testingcell typecomparativedriving forceeggendosymbiontfemale fertilityflygermline stem cellshuman pathogenimprovedinnovationinsightloss of functionmalemutantnovelnull mutationpressurereference genomereproductiveself-renewalsperm cellstem cell differentiationstem cell divisionstem cell functionstem cell genesstem cellssymbionttooltranscriptome sequencingtransmission process
中文摘要
项目摘要
动物含有少量的生殖干细胞(GSC),这些细胞对于制造精子或卵子至关重要。
决定一个分裂的干细胞更新自己或分化,并调节早期GSC分裂
是发展中最关键的过程。对果蝇的研究,黑腹果蝇,
确定了许多参与GSC维持和分化的细胞信号传导的关键基因。我们
已经表明,大理石基因袋(bam),GSC分化的关键“开关”,是适应性进化的
在D. melanogaster、黑腹果蝇D. simulans、D.日本料理,但不是在六
其他相关物种。在我们目前的资助期间,我们已经产生了新的bam无效突变,
D. melanogaster、黑腹果蝇D. simulans,拟谷盗D. yakuba,尖吻隐翅虫D. teissieri和D. ananassae测试
功能守恒。这使我们能够证明,令人惊讶的是,与D。黑腹动物,
bam对雌性D.也不是雄性GSC分化所必需的
in D. teissieri和D. ananassae。我们已经证明,感染不同菌株的细胞内
内共生体Wolbachia pipientis在挽救bam的生育缺陷特征方面的程度各不相同
亚型这项建议的重点是确定所观察到的功能和进化后果,
bam的序列多样性,并区分bam在GSC功能中的作用
已被选定为新的功能,与假设之间的相互作用bam和W。皮皮恩蒂斯河
是推动巴姆变革的进化力量这包括生成和分析新的bam
D. melanogaster和D. simulans,并测试这些新的hypomorphs与intra
和种间沃尔巴克氏体菌株。我们将对W. pipientis。我们
正在开发一个计算模型,以产生实验可检验的序列预测,
在W. pipientis和GSC基因。最后我们将
在功能上评估D. melanogaster和D.
simulans的雌、雄配子体发育和育性对bam的需求消失。
teissieri与近缘种D.日本料理。我们学到的东西将大大有助于我们的
了解GSC在不同物种发育过程中的调节方式,
发育功能可以进化,以及它们如何由于突变和与
生殖系寄生虫可导致不育、生殖系癌症和生殖隔离。
英文摘要
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.
期刊论文(13)
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DOI:
10.1534/g3.114.015875
发表时间:
2015-02-09
期刊:
G3 (Bethesda, Md.)
影响因子:
--
作者:
[Flores HA, DuMont VL, Fatoo A, Hubbard D, Hijji M, Barbash DA, Aquadro CF]
通讯作者:
Aquadro CF
DOI:
10.1371/journal.pgen.1005453
发表时间:
2015-08
期刊:
PLoS genetics
影响因子:
4.5
作者:
[Flores HA, Bubnell JE, Aquadro CF, Barbash DA]
通讯作者:
Barbash DA
DOI:
10.1007/s00239-016-9753-9
发表时间:
2016-08
期刊:
JOURNAL OF MOLECULAR EVOLUTION
影响因子:
3.9
作者:
[Choi, Jae Young, Aquadro, Charles F.]
通讯作者:
Aquadro, Charles F.
DOI:
10.1371/journal.pgen.1011009
发表时间:
2023-10
期刊:
PLoS genetics
影响因子:
4.5
作者:
[]
通讯作者:
DOI:
10.1093/gbe/evv158
发表时间:
2015-08-08
期刊:
Genome biology and evolution
影响因子:
3.3
作者:
[Choi JY, Bubnell JE, Aquadro CF]
通讯作者:
Aquadro CF
共 10 条
Adaptive Protein Evolution of the Drosophila Germline Stem Cell Gene Bag of Marbles
-
批准号:10459566
-
项目类别:
-
资助金额:$33.76万
-
财政年份:2011
-
负责人:CHARLES F AQUADRO
-
依托单位:
Adaptive protein evolution of the Drosophila germline stem cell gene bag of marbles
-
批准号:9353828
-
项目类别:
-
资助金额:$32.31万
-
财政年份:2011
-
负责人:CHARLES F AQUADRO
-
依托单位:
Adaptive protein evolution of_Drosophila_germline stem cell genes_bam_and_bgcn_
-
批准号:8512742
-
项目类别:
-
资助金额:$29.91万
-
财政年份:2011
-
负责人:CHARLES F AQUADRO
-
依托单位:
Adaptive protein evolution of the Drosophila germline stem cell gene bag of marbles
-
批准号:9509464
-
项目类别:
-
资助金额:$32.27万
-
财政年份:2011
-
负责人:CHARLES F AQUADRO
-
依托单位:
Adaptive protein evolution of_Drosophila_germline stem cell genes_bam_and_bgcn_
-
批准号:8306723
-
项目类别:
-
资助金额:$31.01万
-
财政年份:2011
-
负责人:CHARLES F AQUADRO
-
依托单位:
Adaptive protein evolution of_Drosophila_germline stem cell genes_bam_and_bgcn_
-
批准号:8708121
-
项目类别:
-
资助金额:$30.98万
-
财政年份:2011
-
负责人:CHARLES F AQUADRO
-
依托单位:
Adaptive Protein Evolution of the Drosophila Germline Stem Cell Gene Bag of Marbles
-
批准号:10298579
-
项目类别:
-
资助金额:$33.76万
-
财政年份:2011
-
负责人:CHARLES F AQUADRO
-
依托单位:
Adaptive protein evolution of_Drosophila_germline stem cell genes_bam_and_bgcn_
-
批准号:8187760
-
项目类别:
-
资助金额:$31.02万
-
财政年份:2011
-
负责人:CHARLES F AQUADRO
-
依托单位:
ABI PRISM MODEL 377 DNA SEQUENCER
-
批准号:2803464
-
项目类别:
-
资助金额:$13.91万
-
财政年份:1999
-
负责人:CHARLES F AQUADRO
-
依托单位:
COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA
-
批准号:2178362
-
项目类别:
-
资助金额:$22.28万
-
财政年份:1986
-
负责人:CHARLES F AQUADRO
-
依托单位:
Comparative Molecular Population Genetics of Drosophila
-
批准号:7933883
-
项目类别:
-
资助金额:$37.04万
-
财政年份:1986
-
负责人:CHARLES F AQUADRO
-
依托单位:
COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA
-
批准号:2391997
-
项目类别:
-
资助金额:$23.97万
-
财政年份:1986
-
负责人:CHARLES F AQUADRO
-
依托单位:
COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA
-
批准号:2178363
-
项目类别:
-
资助金额:$22.86万
-
财政年份:1986
-
负责人:CHARLES F AQUADRO
-
依托单位:
COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA
-
批准号:6901085
-
项目类别:
-
资助金额:$30.95万
-
财政年份:1986
-
负责人:CHARLES F AQUADRO
-
依托单位:
COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA
-
批准号:3290397
-
项目类别:
-
资助金额:$20.75万
-
财政年份:1986
-
负责人:CHARLES F AQUADRO
-
依托单位:
COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA
-
批准号:2900623
-
项目类别:
-
资助金额:$32.21万
-
财政年份:1986
-
负责人:CHARLES F AQUADRO
-
依托单位:
MOLECULAR POPULATION GENETICS OF DROSOPHILA MELANOGASTER
-
批准号:3290390
-
项目类别:
-
资助金额:$13.42万
-
财政年份:1986
-
负责人:CHARLES F AQUADRO
-
依托单位:
MOLECULAR POPULATION GENETICS OF DROSOPHILA MELANOGASTER
-
批准号:3290392
-
项目类别:
-
资助金额:$16.02万
-
财政年份:1986
-
负责人:CHARLES F AQUADRO
-
依托单位:
COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA
-
批准号:2178361
-
项目类别:
-
资助金额:$22.77万
-
财政年份:1986
-
负责人:CHARLES F AQUADRO
-
依托单位:
COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA
-
批准号:3290391
-
项目类别:
-
资助金额:$18.73万
-
财政年份:1986
-
负责人:CHARLES F AQUADRO
-
依托单位:
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