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Loss of heterozygosity by SCRaMbLEing.

Identifieur interne : 000290 ( Main/Exploration ); précédent : 000289; suivant : 000291

Loss of heterozygosity by SCRaMbLEing.

Auteurs : Yunxiang Li [République populaire de Chine] ; Yi Wu [République populaire de Chine] ; Lu Ma [République populaire de Chine] ; Zhou Guo [République populaire de Chine] ; Wenhai Xiao [République populaire de Chine] ; Yingjin Yuan [République populaire de Chine]

Source :

RBID : pubmed:30900161

Descripteurs français

English descriptors

Abstract

Genetic variation drives phenotypic evolution within populations. Genetic variation can be divided into different forms according to the size of genomic changes. However, study of large-scale genomic variation such as structural variation and aneuploidy is still limited and mainly based on the static, predetermined feature of individual genomes. Here, using SCRaMbLE, different levels of loss of heterozygosity (LOH) events including short-range LOH, long-range LOH and whole chromosome LOH were detected in evolved strains. By contrast, using rapid adaptive evolution, aneuploidy was detected in the adaptive strains. It was further found that deletion of gene GLN3, long-range LOH in the left arm of synthetic chromosome X, whole chromosome LOH of synthetic chromosome X, and duplication of chromosome VIII (trisomy) lead to increased rapamycin resistance in synthetic yeast. Comparative analysis of genome stability of evolved strains indicates that the aneuploid strain has a higher frequency of degeneration than the SCRaMbLEd strain. These findings enrich our understanding of genetic mechanism of rapamycin resistance in yeast, and provide valuable insights into yeast genome architecture and function.

DOI: 10.1007/s11427-019-9504-5
PubMed: 30900161


Affiliations:


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<term>Aneuploidy (MeSH)</term>
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<term>Drug Resistance, Microbial (drug effects)</term>
<term>Drug Resistance, Microbial (genetics)</term>
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<div type="abstract" xml:lang="en">Genetic variation drives phenotypic evolution within populations. Genetic variation can be divided into different forms according to the size of genomic changes. However, study of large-scale genomic variation such as structural variation and aneuploidy is still limited and mainly based on the static, predetermined feature of individual genomes. Here, using SCRaMbLE, different levels of loss of heterozygosity (LOH) events including short-range LOH, long-range LOH and whole chromosome LOH were detected in evolved strains. By contrast, using rapid adaptive evolution, aneuploidy was detected in the adaptive strains. It was further found that deletion of gene GLN3, long-range LOH in the left arm of synthetic chromosome X, whole chromosome LOH of synthetic chromosome X, and duplication of chromosome VIII (trisomy) lead to increased rapamycin resistance in synthetic yeast. Comparative analysis of genome stability of evolved strains indicates that the aneuploid strain has a higher frequency of degeneration than the SCRaMbLEd strain. These findings enrich our understanding of genetic mechanism of rapamycin resistance in yeast, and provide valuable insights into yeast genome architecture and function.</div>
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<Affiliation>Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China.</Affiliation>
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<AffiliationInfo>
<Affiliation>Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.</Affiliation>
</AffiliationInfo>
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<ForeName>Wenhai</ForeName>
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<AffiliationInfo>
<Affiliation>Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Yuan</LastName>
<ForeName>Yingjin</ForeName>
<Initials>Y</Initials>
<AffiliationInfo>
<Affiliation>Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China. yjyuan@tju.edu.cn.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China. yjyuan@tju.edu.cn.</Affiliation>
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<Year>2019</Year>
<Month>03</Month>
<Day>01</Day>
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<Country>China</Country>
<MedlineTA>Sci China Life Sci</MedlineTA>
<NlmUniqueID>101529880</NlmUniqueID>
<ISSNLinking>1674-7305</ISSNLinking>
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<Chemical>
<RegistryNumber>0</RegistryNumber>
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<Chemical>
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<RefSource>Sci China Life Sci. 2019 Jun;62(6):868-869</RefSource>
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</CommentsCorrections>
</CommentsCorrectionsList>
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<DescriptorName UI="D000782" MajorTopicYN="Y">Aneuploidy</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D015825" MajorTopicYN="N">Chromosomes, Fungal</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004352" MajorTopicYN="N">Drug Resistance, Microbial</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
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<MeshHeading>
<DescriptorName UI="D014644" MajorTopicYN="N">Genetic Variation</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D016681" MajorTopicYN="N">Genome, Fungal</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D042822" MajorTopicYN="N">Genomic Instability</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D006579" MajorTopicYN="N">Heterozygote</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D019656" MajorTopicYN="N">Loss of Heterozygosity</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D010641" MajorTopicYN="N">Phenotype</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D012441" MajorTopicYN="N">Saccharomyces cerevisiae</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D029701" MajorTopicYN="N">Saccharomyces cerevisiae Proteins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D020123" MajorTopicYN="N">Sirolimus</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014157" MajorTopicYN="N">Transcription Factors</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM">
<Keyword MajorTopicYN="N">SCRaMbLE</Keyword>
<Keyword MajorTopicYN="N">aneuploidy</Keyword>
<Keyword MajorTopicYN="N">loss of heterozygosity (LOH)</Keyword>
<Keyword MajorTopicYN="N">rapid adaptive evolution</Keyword>
<Keyword MajorTopicYN="N">structural variation</Keyword>
<Keyword MajorTopicYN="N">synthetic yeast genome</Keyword>
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</MedlineCitation>
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<PubMedPubDate PubStatus="received">
<Year>2019</Year>
<Month>01</Month>
<Day>15</Day>
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<PubMedPubDate PubStatus="accepted">
<Year>2019</Year>
<Month>02</Month>
<Day>19</Day>
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<Year>2019</Year>
<Month>3</Month>
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<Hour>6</Hour>
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<Month>3</Month>
<Day>10</Day>
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<Year>2019</Year>
<Month>3</Month>
<Day>23</Day>
<Hour>6</Hour>
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<ArticleId IdType="doi">10.1007/s11427-019-9504-5</ArticleId>
<ArticleId IdType="pii">10.1007/s11427-019-9504-5</ArticleId>
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<list>
<country>
<li>République populaire de Chine</li>
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<name sortKey="Li, Yunxiang" sort="Li, Yunxiang" uniqKey="Li Y" first="Yunxiang" last="Li">Yunxiang Li</name>
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<name sortKey="Guo, Zhou" sort="Guo, Zhou" uniqKey="Guo Z" first="Zhou" last="Guo">Zhou Guo</name>
<name sortKey="Guo, Zhou" sort="Guo, Zhou" uniqKey="Guo Z" first="Zhou" last="Guo">Zhou Guo</name>
<name sortKey="Li, Yunxiang" sort="Li, Yunxiang" uniqKey="Li Y" first="Yunxiang" last="Li">Yunxiang Li</name>
<name sortKey="Ma, Lu" sort="Ma, Lu" uniqKey="Ma L" first="Lu" last="Ma">Lu Ma</name>
<name sortKey="Ma, Lu" sort="Ma, Lu" uniqKey="Ma L" first="Lu" last="Ma">Lu Ma</name>
<name sortKey="Wu, Yi" sort="Wu, Yi" uniqKey="Wu Y" first="Yi" last="Wu">Yi Wu</name>
<name sortKey="Wu, Yi" sort="Wu, Yi" uniqKey="Wu Y" first="Yi" last="Wu">Yi Wu</name>
<name sortKey="Xiao, Wenhai" sort="Xiao, Wenhai" uniqKey="Xiao W" first="Wenhai" last="Xiao">Wenhai Xiao</name>
<name sortKey="Xiao, Wenhai" sort="Xiao, Wenhai" uniqKey="Xiao W" first="Wenhai" last="Xiao">Wenhai Xiao</name>
<name sortKey="Yuan, Yingjin" sort="Yuan, Yingjin" uniqKey="Yuan Y" first="Yingjin" last="Yuan">Yingjin Yuan</name>
<name sortKey="Yuan, Yingjin" sort="Yuan, Yingjin" uniqKey="Yuan Y" first="Yingjin" last="Yuan">Yingjin Yuan</name>
</country>
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</affiliations>
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