Genetic Conflict Shapes Centromeres and Heterochromatin
Genetic Conflict Shapes Centromeres and Heterochromatin
批准号:
10654557
负责人:
HARMIT S MALIK
金额:
$37.4万
依托单位国家:
美国
项目类别:
财政年份:
2005
资助国家:
美国
项目状态:
已结题
起止时间:
2005-07-01 至 2024-05-31
关键词:
AddressAdoptedAllelesAmino Acid MotifsAneuploidyAnimalsBehaviorBindingBiologicalBiological ProcessCellular biologyCentromereChromatidsChromosome SegregationChromosome abnormalityChromosomesConflict (Psychology)Congenital AbnormalityCytologyDNADNA Sequence AlterationDefectDepositionDown SyndromeDrosophila genusEmbryoEmbryonic DevelopmentEngineeringEnsureEpigenetic ProcessEukaryotaEvolutionFemaleFoundationsGene DuplicationGenesGeneticGenetic ModelsGenetic studyGenomeGenome engineeringHeterochromatinHistone H3HistonesInfertilityInheritedKinetochoresLeadMalignant NeoplasmsMediatingMeiosisMicrotubulesMitosisMitoticModelingMolecularMusNematodaOocytesOogenesisPhenotypePlantsProcessProteinsProteomicsRecurrenceRestRoleSatellite DNAShapesSiteSpermiogenesisTestingTransgenesVariantYeastsbasecostdevelopmental diseaseeggexpectationexperiencefitnessflygenetic analysisinsightinterdisciplinary approachknock-downneuronal cell bodyparalogous genepleiotropismprotein protein interactionrecruitsperm celltooltransmission process
中文摘要
项目总结
染色体分离是一个必不可少的过程。关键的染色体位置
确保染色体的适当分离是着丝粒,它绑定了微管
在减数分裂和有丝分裂期间将染色体或染色单体分开。着丝粒
因此,功能对染色体分离至关重要。有缺陷的着丝粒可能导致
到非整倍体、不孕不育和唐氏综合症之类的出生缺陷。尽管
染色体分离过程的保守性,着丝粒蛋白如CenH3,
它结合着丝粒DNA来组装微管招募运动中心,进化
在亲缘关系密切的物种之间迅速传播。它们的快速进化是意想不到的,可能
危及染色体分离过程的保真度。我们之前曾提出
这种快速进化是由于“着丝粒驱动”,即
在雌性减数分裂过程中,四个减数分裂产物中只有一个是
被选为卵原核。使用一种结合了以下见解的方法
进化遗传学和细胞生物学,以及最先进的基因组工程工具,我们
建议在果蝇物种中测试这种遗传冲突模型。此外,基于
关于我们在果蝇物种中发现的CenH3反复重复的情况,我们将测试
体细胞着丝粒和生殖系着丝粒功能是否具有不同的功能
限制,这是最容易通过基因复制和特化解决的
CenH3基因。
英文摘要
PROJECT SUMMARY
Chromosome segregation is an essential process. The key chromosomal sites that
ensure proper segregation of chromosomes are centromeres, which bind microtubules
that pull chromosomes or chromatids apart during meiosis and mitosis. Centromere
function is thus essential for chromosome segregation. Defective centromeres can lead
to aneuploidy, infertility, and birth defects like Down’s syndrome. Despite the
conservation of the chromosome segregation process, centromeric proteins like CenH3,
which bind centromeric DNA to assemble microtubule-recruiting kinetochores, evolve
rapidly between closely related species. Their rapid evolution is unexpected and could
imperil the fidelity of the chromosome segregation process. We previously proposed that
this rapid evolution occurs due to ‘centromere-drive’, i.e., competition between
chromosomes during female meiosis, in which only one of four meiotic products is
chosen to be the egg pronucleus. Using an approach that combines insights from
evolutionary genetics and cell biology, and state-of-the-art genome engineering tools, we
propose to test this model of genetic conflict in Drosophila species. Furthermore, based
on our finding of recurrent duplication of CenH3 in Drosophila species, we will test
whether somatic versus germline centromeric functions have different functional
constraints, which are easiest to resolve via gene duplication and specialization of
CenH3 genes.
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Molecular evolution of Drosophila Cdc6, an essential DNA replication-licensing gene, suggests an adaptive choice of replication origins.
果蝇 Cdc6(一种重要的 DNA 复制许可基因)的分子进化表明复制起点的适应性选择。
DOI:
10.4161/fly.4599
发表时间:
2007
期刊:
Fly
影响因子:
1.2
作者:
[Wiggins,BenjaminL, Malik,HarmitS]
通讯作者:
Malik,HarmitS
DOI:
10.1371/journal.pgen.1008520
发表时间:
2019
期刊:
PLoS genetics
影响因子:
4.5
作者:
[Lamelza,Piero, Young,JanetM, Noble,LukeM, Caro,Lews, Isakharov,Arielle, Palanisamy,Meenakshi, Rockman,MatthewV, Malik,HarmitS, Ailion,Michael]
通讯作者:
Ailion,Michael
Genetics: Master Regulator or Master of Disguise?
遗传学:监管大师还是伪装大师?
DOI:
10.1016/j.cub.2017.07.030
发表时间:
2017
期刊:
Current biology : CB
影响因子:
--
作者:
[Ailion,Michael, Malik,HarmitS]
通讯作者:
Malik,HarmitS
A mitochondrial DNA hypomorph of cytochrome oxidase specifically impairs male fertility in Drosophila melanogaster.
细胞色素氧化酶的线粒体 DNA 亚型特别损害果蝇的雄性生育能力。
DOI:
10.7554/elife.16923
发表时间:
2016
期刊:
eLife
影响因子:
7.7
作者:
[Patel,MaulikR, Miriyala,GaneshK, Littleton,AimeeJ, Yang,Heiko, Trinh,Kien, Young,JanetM, Kennedy,ScottR, Yamashita,YukikoM, Pallanck,LeoJ, Malik,HarmitS]
通讯作者:
Malik,HarmitS
DOI:
10.1101/gad.280941.116
发表时间:
2016-05-15
期刊:
Genes & development
影响因子:
10.5
作者:
[Franks TM, Benner C, Narvaiza I, Marchetto MC, Young JM, Malik HS, Gage FH, Hetzer MW]
通讯作者:
Hetzer MW
共 42 条
eDyNAmiC - FREDHUTCH
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批准号:10625801
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项目类别:
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资助金额:$16.55万
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财政年份:2022
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负责人:HARMIT S MALIK
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eDyNAmiC - FREDHUTCH
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资助金额:$22.0万
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财政年份:2012
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负责人:HARMIT S MALIK
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依托单位:
Poxviral antagonism of the IFIT-mediated antiviral response
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项目类别:
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资助金额:$24.82万
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财政年份:2012
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负责人:HARMIT S MALIK
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依托单位:
Genetic conflict shapes centromeres and heterochromatin
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批准号:7251925
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项目类别:
-
资助金额:$32.06万
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财政年份:2005
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负责人:HARMIT S MALIK
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依托单位:
Genetic Conflict Shapes Centromeres and Heterochromatin
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批准号:9039091
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项目类别:
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资助金额:$35.22万
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财政年份:2005
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负责人:HARMIT S MALIK
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依托单位:
Genetic conflict shapes centromeres and heterochromatin
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批准号:8101936
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项目类别:
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资助金额:$35.87万
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Genetic conflict shapes centromeres and heterochromatin
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批准号:8890953
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资助金额:$11.53万
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负责人:HARMIT S MALIK
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依托单位:
Genetic Conflict Shapes Centromeres and Heterochromatin
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批准号:9221343
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项目类别:
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资助金额:$35.16万
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财政年份:2005
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负责人:HARMIT S MALIK
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依托单位:
Genetic Conflict Shapes Centromeres and Heterochromatin
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批准号:8888585
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项目类别:
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资助金额:$35.3万
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财政年份:2005
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负责人:HARMIT S MALIK
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依托单位:
Genetic Conflict Shapes Centromeres and Heterochromatin
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批准号:10411940
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项目类别:
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资助金额:$20.32万
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财政年份:2005
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负责人:HARMIT S MALIK
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依托单位:
Genetic conflict shapes centromeres and heterochromatin
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批准号:8292291
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项目类别:
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资助金额:$35.85万
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财政年份:2005
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负责人:HARMIT S MALIK
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依托单位:
Genetic conflict shapes centromeres and heterochromatin
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批准号:6910492
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项目类别:
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资助金额:$36.56万
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财政年份:2005
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负责人:HARMIT S MALIK
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依托单位:
Genetic conflict shapes centromeres and heterochromatin
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批准号:7629567
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项目类别:
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资助金额:$33.02万
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财政年份:2005
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负责人:HARMIT S MALIK
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依托单位:
Genetic conflict shapes centromeres and heterochromatin
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批准号:7447380
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项目类别:
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资助金额:$32.06万
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财政年份:2005
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负责人:HARMIT S MALIK
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依托单位:
Genetic Conflict Shapes Centromeres and Heterochromatin
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批准号:10004659
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项目类别:
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资助金额:$37.4万
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财政年份:2005
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负责人:HARMIT S MALIK
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依托单位:
Genetic conflict shapes centromeres and heterochromatin
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批准号:7067193
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项目类别:
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资助金额:$32.06万
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财政年份:2005
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负责人:HARMIT S MALIK
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依托单位:
Genetic conflict shapes centromeres and heterochromatin
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批准号:8499346
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项目类别:
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资助金额:$34.58万
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财政年份:2005
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负责人:HARMIT S MALIK
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依托单位:
Genetic conflict shapes centromeres and heterochromatin
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批准号:7986005
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项目类别:
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资助金额:$36.26万
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财政年份:2005
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负责人:HARMIT S MALIK
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依托单位:
海外基金