Equilibrium Distributions of Microsatellite Repeat Length Resulting from a Balance between Slippage Events and Point Mutations
We describe and test a Markov chain model of microsatellite evolution that can explain the different distributions of microsatellite lengths across different organisms and repeat motifs. Two key features of this model are the dependence of mutation rates on microsatellite length and a mutation proce...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1998-09, Vol.95 (18), p.10774-10778 |
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creator | Kruglyak, Semyon Durrett, Richard T. Schug, Malcolm D. Aquadro, Charles F. |
description | We describe and test a Markov chain model of microsatellite evolution that can explain the different distributions of microsatellite lengths across different organisms and repeat motifs. Two key features of this model are the dependence of mutation rates on microsatellite length and a mutation process that includes both strand slippage and point mutation events. We compute the stationary distribution of allele lengths under this model and use it to fit DNA data for di-, tri-, and tetranucleotide repeats in humans, mice, fruit flies, and yeast. The best fit results lead to slippage rate estimates that are highest in mice, followed by humans, then yeast, and then fruit flies. Within each organism, the estimates are highest in di-, then tri-, and then tetranucleotide repeats. Our estimates are consistent with experimentally determined mutation rates from other studies. The results suggest that the different length distributions among organisms and repeat motifs can be explained by a simple difference in slippage rates and that selective constraints on length need not be imposed. |
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Two key features of this model are the dependence of mutation rates on microsatellite length and a mutation process that includes both strand slippage and point mutation events. We compute the stationary distribution of allele lengths under this model and use it to fit DNA data for di-, tri-, and tetranucleotide repeats in humans, mice, fruit flies, and yeast. The best fit results lead to slippage rate estimates that are highest in mice, followed by humans, then yeast, and then fruit flies. Within each organism, the estimates are highest in di-, then tri-, and then tetranucleotide repeats. Our estimates are consistent with experimentally determined mutation rates from other studies. The results suggest that the different length distributions among organisms and repeat motifs can be explained by a simple difference in slippage rates and that selective constraints on length need not be imposed.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.95.18.10774</identifier><identifier>PMID: 9724780</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Alleles ; Animals ; Biological Sciences ; DNA ; Evolution, Molecular ; Genetic loci ; Genetic mutation ; Genetics ; Humans ; Markov Chains ; Microsatellite Repeats ; Microsatellites ; Models, Genetic ; Mutation ; Nucleotides ; Organisms ; Point Mutation ; Yeasts</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1998-09, Vol.95 (18), p.10774-10778</ispartof><rights>Copyright 1993-1998 National Academy of Sciences</rights><rights>Copyright National Academy of Sciences Sep 1, 1998</rights><rights>Copyright © 1998, The National Academy of Sciences 1998</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c589t-70e709b326f585ffd1d0de2b0c6e7722a8f5350557d0da4b6c1d7246081763e43</citedby><cites>FETCH-LOGICAL-c589t-70e709b326f585ffd1d0de2b0c6e7722a8f5350557d0da4b6c1d7246081763e43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/95/18.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/45967$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/45967$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9724780$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kruglyak, Semyon</creatorcontrib><creatorcontrib>Durrett, Richard T.</creatorcontrib><creatorcontrib>Schug, Malcolm D.</creatorcontrib><creatorcontrib>Aquadro, Charles F.</creatorcontrib><title>Equilibrium Distributions of Microsatellite Repeat Length Resulting from a Balance between Slippage Events and Point Mutations</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We describe and test a Markov chain model of microsatellite evolution that can explain the different distributions of microsatellite lengths across different organisms and repeat motifs. Two key features of this model are the dependence of mutation rates on microsatellite length and a mutation process that includes both strand slippage and point mutation events. We compute the stationary distribution of allele lengths under this model and use it to fit DNA data for di-, tri-, and tetranucleotide repeats in humans, mice, fruit flies, and yeast. The best fit results lead to slippage rate estimates that are highest in mice, followed by humans, then yeast, and then fruit flies. Within each organism, the estimates are highest in di-, then tri-, and then tetranucleotide repeats. Our estimates are consistent with experimentally determined mutation rates from other studies. The results suggest that the different length distributions among organisms and repeat motifs can be explained by a simple difference in slippage rates and that selective constraints on length need not be imposed.</description><subject>Alleles</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>DNA</subject><subject>Evolution, Molecular</subject><subject>Genetic loci</subject><subject>Genetic mutation</subject><subject>Genetics</subject><subject>Humans</subject><subject>Markov Chains</subject><subject>Microsatellite Repeats</subject><subject>Microsatellites</subject><subject>Models, Genetic</subject><subject>Mutation</subject><subject>Nucleotides</subject><subject>Organisms</subject><subject>Point Mutation</subject><subject>Yeasts</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuP0zAQxiMEWsrCHSEhLA6IS8rYieNY4gJLeUhdgXicLSeZdF2ldtZ2Frjwt-Nsq_I4wMkaz--b15dl9yksKYji2Wh1WEq-pPUci_JGtqAgaV6VEm5mCwAm8rpk5e3sTghbAJC8hpPsRApWihoW2Y_V5WQG03gz7cgrE6I3zRSNs4G4npyb1rugIw6DiUg-4og6kjXaTbxIUZiGaOyG9N7tiCYv9aBti6TB-BXRkk-DGUe9QbK6QhsD0bYjH5yxkZxPUV83uZvd6vUQ8N7hPc2-vF59Pnubr9-_eXf2Yp23vJYxF4ACZFOwquc17_uOdtAha6CtUAjGdN3zggPnIv3rsqla2qUNK6ipqAosi9Ps-b7uODU77No0j9eDGr3Zaf9dOW3UnxlrLtTGXSkmpKBJ_uQg9-5ywhDVzoQ2XUVbdFNQopBQVxX7L0grzkvBZ_DxX-DWTd6mGygGNC3K5NwW9tDsQvDYHwemoGb_1ey_klzRWl37nyQPf1_0KDgYnvJPD_lZecz-qqD6aRgifosJffRvNBEP9sQ2ROePSMllJYqfHYvP2w</recordid><startdate>19980901</startdate><enddate>19980901</enddate><creator>Kruglyak, Semyon</creator><creator>Durrett, Richard T.</creator><creator>Schug, Malcolm D.</creator><creator>Aquadro, Charles F.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><general>The National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19980901</creationdate><title>Equilibrium Distributions of Microsatellite Repeat Length Resulting from a Balance between Slippage Events and Point Mutations</title><author>Kruglyak, Semyon ; 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Two key features of this model are the dependence of mutation rates on microsatellite length and a mutation process that includes both strand slippage and point mutation events. We compute the stationary distribution of allele lengths under this model and use it to fit DNA data for di-, tri-, and tetranucleotide repeats in humans, mice, fruit flies, and yeast. The best fit results lead to slippage rate estimates that are highest in mice, followed by humans, then yeast, and then fruit flies. Within each organism, the estimates are highest in di-, then tri-, and then tetranucleotide repeats. Our estimates are consistent with experimentally determined mutation rates from other studies. 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subjects | Alleles Animals Biological Sciences DNA Evolution, Molecular Genetic loci Genetic mutation Genetics Humans Markov Chains Microsatellite Repeats Microsatellites Models, Genetic Mutation Nucleotides Organisms Point Mutation Yeasts |
title | Equilibrium Distributions of Microsatellite Repeat Length Resulting from a Balance between Slippage Events and Point Mutations |
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