Natural genetic variation in yeast longevity

The genetics of aging in the yeast Saccharomyces cerevisiae has involved the manipulation of individual genes in laboratory strains. We have instituted a quantitative genetic analysis of the yeast replicative lifespan by sampling the natural genetic variation in a wild yeast isolate. Haploid segrega...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Genome research 2012-10, Vol.22 (10), p.1963-1973
Hauptverfasser: Stumpferl, Stefan W, Brand, Sue E, Jiang, James C, Korona, Boguslawa, Tiwari, Anurag, Dai, Jianliang, Seo, Jae-Gu, Jazwinski, S Michal
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1973
container_issue 10
container_start_page 1963
container_title Genome research
container_volume 22
creator Stumpferl, Stefan W
Brand, Sue E
Jiang, James C
Korona, Boguslawa
Tiwari, Anurag
Dai, Jianliang
Seo, Jae-Gu
Jazwinski, S Michal
description The genetics of aging in the yeast Saccharomyces cerevisiae has involved the manipulation of individual genes in laboratory strains. We have instituted a quantitative genetic analysis of the yeast replicative lifespan by sampling the natural genetic variation in a wild yeast isolate. Haploid segregants from a cross between a common laboratory strain (S288c) and a clinically derived strain (YJM145) were subjected to quantitative trait locus (QTL) analysis, using 3048 molecular markers across the genome. Five significant, replicative lifespan QTL were identified. Among them, QTL 1 on chromosome IV has the largest effect and contains SIR2, whose product differs by five amino acids in the parental strains. Reciprocal gene swap experiments showed that this gene is responsible for the majority of the effect of this QTL on lifespan. The QTL with the second-largest effect on longevity was QTL 5 on chromosome XII, and the bulk of the underlying genomic sequence contains multiple copies (100-150) of the rDNA. Substitution of the rDNA clusters of the parental strains indicated that they play a predominant role in the effect of this QTL on longevity. This effect does not appear to simply be a function of extrachromosomal ribosomal DNA circle production. The results support an interaction between SIR2 and the rDNA locus, which does not completely explain the effect of these loci on longevity. This study provides a glimpse of the complex genetic architecture of replicative lifespan in yeast and of the potential role of genetic variation hitherto unsampled in the laboratory.
doi_str_mv 10.1101/gr.136549.111
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3460191</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1082235762</sourcerecordid><originalsourceid>FETCH-LOGICAL-c486t-7797a77aa051b20733a5522fc98d04b75dce5cd1a09f0e9b6b747350c79ee80f3</originalsourceid><addsrcrecordid>eNqFkU1PwzAMhiMEYmNw5Ip65EDBSZqvCxKa-JImuMA5Sru0BHXtSNJJ-_dk2pjgxMm2_Oj1axuhcwzXGAO-afw1ppwVKpX4AI1xSnNWcHWYcpAyV8DwCJ2E8AkAtJDyGI0IUYzhAsbo6sXEwZs2a2xno6uylfHORNd3meuytTUhZm3fNXbl4voUHdWmDfZsFyfo_eH-bfqUz14fn6d3s7wqJI-5EEoYIYxJk0sCglLDGCF1peQcilKweWVZNccGVA1WlbwUhaAMKqGslVDTCbrd6i6HcmET3cVkUS-9Wxi_1r1x-m-ncx-66VeaFhywwkngcifg-6_BhqgXLlS2bU1n-yFozJMpCUzy_1GQhFAmOElovkUr34fgbb13hEFvnqEbr7fPSOXGxcXvNfb0z_XpNws0hI8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1082235762</pqid></control><display><type>article</type><title>Natural genetic variation in yeast longevity</title><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Stumpferl, Stefan W ; Brand, Sue E ; Jiang, James C ; Korona, Boguslawa ; Tiwari, Anurag ; Dai, Jianliang ; Seo, Jae-Gu ; Jazwinski, S Michal</creator><creatorcontrib>Stumpferl, Stefan W ; Brand, Sue E ; Jiang, James C ; Korona, Boguslawa ; Tiwari, Anurag ; Dai, Jianliang ; Seo, Jae-Gu ; Jazwinski, S Michal</creatorcontrib><description>The genetics of aging in the yeast Saccharomyces cerevisiae has involved the manipulation of individual genes in laboratory strains. We have instituted a quantitative genetic analysis of the yeast replicative lifespan by sampling the natural genetic variation in a wild yeast isolate. Haploid segregants from a cross between a common laboratory strain (S288c) and a clinically derived strain (YJM145) were subjected to quantitative trait locus (QTL) analysis, using 3048 molecular markers across the genome. Five significant, replicative lifespan QTL were identified. Among them, QTL 1 on chromosome IV has the largest effect and contains SIR2, whose product differs by five amino acids in the parental strains. Reciprocal gene swap experiments showed that this gene is responsible for the majority of the effect of this QTL on lifespan. The QTL with the second-largest effect on longevity was QTL 5 on chromosome XII, and the bulk of the underlying genomic sequence contains multiple copies (100-150) of the rDNA. Substitution of the rDNA clusters of the parental strains indicated that they play a predominant role in the effect of this QTL on longevity. This effect does not appear to simply be a function of extrachromosomal ribosomal DNA circle production. The results support an interaction between SIR2 and the rDNA locus, which does not completely explain the effect of these loci on longevity. This study provides a glimpse of the complex genetic architecture of replicative lifespan in yeast and of the potential role of genetic variation hitherto unsampled in the laboratory.</description><identifier>ISSN: 1088-9051</identifier><identifier>EISSN: 1549-5469</identifier><identifier>DOI: 10.1101/gr.136549.111</identifier><identifier>PMID: 22955140</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Chromosome Mapping ; DNA, Ribosomal - genetics ; Gene Expression Regulation, Fungal ; Genetic Variation ; Longevity ; Molecular Sequence Data ; Quantitative Trait Loci ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae - genetics ; Saccharomyces cerevisiae - growth &amp; development ; Silent Information Regulator Proteins, Saccharomyces cerevisiae - genetics ; Sirtuin 2 - genetics ; Transcription, Genetic</subject><ispartof>Genome research, 2012-10, Vol.22 (10), p.1963-1973</ispartof><rights>2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-7797a77aa051b20733a5522fc98d04b75dce5cd1a09f0e9b6b747350c79ee80f3</citedby><cites>FETCH-LOGICAL-c486t-7797a77aa051b20733a5522fc98d04b75dce5cd1a09f0e9b6b747350c79ee80f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460191/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460191/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22955140$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stumpferl, Stefan W</creatorcontrib><creatorcontrib>Brand, Sue E</creatorcontrib><creatorcontrib>Jiang, James C</creatorcontrib><creatorcontrib>Korona, Boguslawa</creatorcontrib><creatorcontrib>Tiwari, Anurag</creatorcontrib><creatorcontrib>Dai, Jianliang</creatorcontrib><creatorcontrib>Seo, Jae-Gu</creatorcontrib><creatorcontrib>Jazwinski, S Michal</creatorcontrib><title>Natural genetic variation in yeast longevity</title><title>Genome research</title><addtitle>Genome Res</addtitle><description>The genetics of aging in the yeast Saccharomyces cerevisiae has involved the manipulation of individual genes in laboratory strains. We have instituted a quantitative genetic analysis of the yeast replicative lifespan by sampling the natural genetic variation in a wild yeast isolate. Haploid segregants from a cross between a common laboratory strain (S288c) and a clinically derived strain (YJM145) were subjected to quantitative trait locus (QTL) analysis, using 3048 molecular markers across the genome. Five significant, replicative lifespan QTL were identified. Among them, QTL 1 on chromosome IV has the largest effect and contains SIR2, whose product differs by five amino acids in the parental strains. Reciprocal gene swap experiments showed that this gene is responsible for the majority of the effect of this QTL on lifespan. The QTL with the second-largest effect on longevity was QTL 5 on chromosome XII, and the bulk of the underlying genomic sequence contains multiple copies (100-150) of the rDNA. Substitution of the rDNA clusters of the parental strains indicated that they play a predominant role in the effect of this QTL on longevity. This effect does not appear to simply be a function of extrachromosomal ribosomal DNA circle production. The results support an interaction between SIR2 and the rDNA locus, which does not completely explain the effect of these loci on longevity. This study provides a glimpse of the complex genetic architecture of replicative lifespan in yeast and of the potential role of genetic variation hitherto unsampled in the laboratory.</description><subject>Chromosome Mapping</subject><subject>DNA, Ribosomal - genetics</subject><subject>Gene Expression Regulation, Fungal</subject><subject>Genetic Variation</subject><subject>Longevity</subject><subject>Molecular Sequence Data</subject><subject>Quantitative Trait Loci</subject><subject>Saccharomyces cerevisiae</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Saccharomyces cerevisiae - growth &amp; development</subject><subject>Silent Information Regulator Proteins, Saccharomyces cerevisiae - genetics</subject><subject>Sirtuin 2 - genetics</subject><subject>Transcription, Genetic</subject><issn>1088-9051</issn><issn>1549-5469</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1PwzAMhiMEYmNw5Ip65EDBSZqvCxKa-JImuMA5Sru0BHXtSNJJ-_dk2pjgxMm2_Oj1axuhcwzXGAO-afw1ppwVKpX4AI1xSnNWcHWYcpAyV8DwCJ2E8AkAtJDyGI0IUYzhAsbo6sXEwZs2a2xno6uylfHORNd3meuytTUhZm3fNXbl4voUHdWmDfZsFyfo_eH-bfqUz14fn6d3s7wqJI-5EEoYIYxJk0sCglLDGCF1peQcilKweWVZNccGVA1WlbwUhaAMKqGslVDTCbrd6i6HcmET3cVkUS-9Wxi_1r1x-m-ncx-66VeaFhywwkngcifg-6_BhqgXLlS2bU1n-yFozJMpCUzy_1GQhFAmOElovkUr34fgbb13hEFvnqEbr7fPSOXGxcXvNfb0z_XpNws0hI8</recordid><startdate>20121001</startdate><enddate>20121001</enddate><creator>Stumpferl, Stefan W</creator><creator>Brand, Sue E</creator><creator>Jiang, James C</creator><creator>Korona, Boguslawa</creator><creator>Tiwari, Anurag</creator><creator>Dai, Jianliang</creator><creator>Seo, Jae-Gu</creator><creator>Jazwinski, S Michal</creator><general>Cold Spring Harbor Laboratory Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20121001</creationdate><title>Natural genetic variation in yeast longevity</title><author>Stumpferl, Stefan W ; Brand, Sue E ; Jiang, James C ; Korona, Boguslawa ; Tiwari, Anurag ; Dai, Jianliang ; Seo, Jae-Gu ; Jazwinski, S Michal</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-7797a77aa051b20733a5522fc98d04b75dce5cd1a09f0e9b6b747350c79ee80f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Chromosome Mapping</topic><topic>DNA, Ribosomal - genetics</topic><topic>Gene Expression Regulation, Fungal</topic><topic>Genetic Variation</topic><topic>Longevity</topic><topic>Molecular Sequence Data</topic><topic>Quantitative Trait Loci</topic><topic>Saccharomyces cerevisiae</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Saccharomyces cerevisiae - growth &amp; development</topic><topic>Silent Information Regulator Proteins, Saccharomyces cerevisiae - genetics</topic><topic>Sirtuin 2 - genetics</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stumpferl, Stefan W</creatorcontrib><creatorcontrib>Brand, Sue E</creatorcontrib><creatorcontrib>Jiang, James C</creatorcontrib><creatorcontrib>Korona, Boguslawa</creatorcontrib><creatorcontrib>Tiwari, Anurag</creatorcontrib><creatorcontrib>Dai, Jianliang</creatorcontrib><creatorcontrib>Seo, Jae-Gu</creatorcontrib><creatorcontrib>Jazwinski, S Michal</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genome research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stumpferl, Stefan W</au><au>Brand, Sue E</au><au>Jiang, James C</au><au>Korona, Boguslawa</au><au>Tiwari, Anurag</au><au>Dai, Jianliang</au><au>Seo, Jae-Gu</au><au>Jazwinski, S Michal</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Natural genetic variation in yeast longevity</atitle><jtitle>Genome research</jtitle><addtitle>Genome Res</addtitle><date>2012-10-01</date><risdate>2012</risdate><volume>22</volume><issue>10</issue><spage>1963</spage><epage>1973</epage><pages>1963-1973</pages><issn>1088-9051</issn><eissn>1549-5469</eissn><abstract>The genetics of aging in the yeast Saccharomyces cerevisiae has involved the manipulation of individual genes in laboratory strains. We have instituted a quantitative genetic analysis of the yeast replicative lifespan by sampling the natural genetic variation in a wild yeast isolate. Haploid segregants from a cross between a common laboratory strain (S288c) and a clinically derived strain (YJM145) were subjected to quantitative trait locus (QTL) analysis, using 3048 molecular markers across the genome. Five significant, replicative lifespan QTL were identified. Among them, QTL 1 on chromosome IV has the largest effect and contains SIR2, whose product differs by five amino acids in the parental strains. Reciprocal gene swap experiments showed that this gene is responsible for the majority of the effect of this QTL on lifespan. The QTL with the second-largest effect on longevity was QTL 5 on chromosome XII, and the bulk of the underlying genomic sequence contains multiple copies (100-150) of the rDNA. Substitution of the rDNA clusters of the parental strains indicated that they play a predominant role in the effect of this QTL on longevity. This effect does not appear to simply be a function of extrachromosomal ribosomal DNA circle production. The results support an interaction between SIR2 and the rDNA locus, which does not completely explain the effect of these loci on longevity. This study provides a glimpse of the complex genetic architecture of replicative lifespan in yeast and of the potential role of genetic variation hitherto unsampled in the laboratory.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>22955140</pmid><doi>10.1101/gr.136549.111</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1088-9051
ispartof Genome research, 2012-10, Vol.22 (10), p.1963-1973
issn 1088-9051
1549-5469
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3460191
source MEDLINE; PubMed Central; Alma/SFX Local Collection
subjects Chromosome Mapping
DNA, Ribosomal - genetics
Gene Expression Regulation, Fungal
Genetic Variation
Longevity
Molecular Sequence Data
Quantitative Trait Loci
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - growth & development
Silent Information Regulator Proteins, Saccharomyces cerevisiae - genetics
Sirtuin 2 - genetics
Transcription, Genetic
title Natural genetic variation in yeast longevity
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T02%3A13%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Natural%20genetic%20variation%20in%20yeast%20longevity&rft.jtitle=Genome%20research&rft.au=Stumpferl,%20Stefan%20W&rft.date=2012-10-01&rft.volume=22&rft.issue=10&rft.spage=1963&rft.epage=1973&rft.pages=1963-1973&rft.issn=1088-9051&rft.eissn=1549-5469&rft_id=info:doi/10.1101/gr.136549.111&rft_dat=%3Cproquest_pubme%3E1082235762%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1082235762&rft_id=info:pmid/22955140&rfr_iscdi=true