Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Bakers Yeast [Genome Integrity and Transmission]

Raghavan, V., Bui, D. T., Al-Sweel, N., Friedrich, A., Schacherer, J., Aquadro, C. F., Alani, E.
Genetics Society of America (GSA)
Published 2018

Publication Date:	2018-12-07
Publisher:	Genetics Society of America (GSA)
Print ISSN:	0016-6731
Topics:	Biology
Published by:	http://www.genetics-gsa.org/

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autor	Raghavan, V., Bui, D. T., Al-Sweel, N., Friedrich, A., Schacherer, J., Aquadro, C. F., Alani, E.
beschreibung	Laboratory baker’s yeast strains bearing an incompatible combination of MLH1 and PMS1 mismatch repair alleles are mutators that can adapt more rapidly to stress, but do so at the cost of long-term fitness. We identified 18 baker’s yeast isolates from 1011 surveyed that contain the incompatible MLH1 - PMS1 genotype in a heterozygous state. Surprisingly, the incompatible combination from two human clinical heterozygous diploid isolates, YJS5845 and YJS5885, contain the exact MLH1 (S288c-derived) and PMS1 (SK1-derived) open reading frames originally shown to confer incompatibility. While these isolates were nonmutators, their meiotic spore clone progeny displayed mutation rates in a DNA slippage assay that varied over a 340-fold range. This range was 30-fold higher than observed between compatible and incompatible combinations of laboratory strains. Genotyping analysis indicated that MLH1 - PMS1 incompatibility was the major driver of mutation rate in the isolates. The variation in the mutation rate of incompatible spore clones could be due to background suppressors and enhancers, as well as aneuploidy seen in the spore clones. Our data are consistent with the observed variance in mutation rate contributing to adaptation to stress conditions ( e.g. , in a human host) through the acquisition of beneficial mutations, with high mutation rates leading to long-term fitness costs that are buffered by mating or eliminated through natural selection.
citation_standardnr	6365898
datenlieferant	ipn_articles
feed_id	2584
feed_publisher	Genetics Society of America (GSA)
feed_publisher_url	http://www.genetics-gsa.org/
insertion_date	2018-12-07
journalissn	0016-6731
publikationsjahr_anzeige	2018
publikationsjahr_facette	2018
publikationsjahr_intervall	7984:2015-2019
publikationsjahr_sort	2018
publisher	Genetics Society of America (GSA)
quelle	Genetics
relation	http://www.genetics.org/cgi/content/short/210/4/1253?rss=1
search_space	articles
shingle_author_1	Raghavan, V., Bui, D. T., Al-Sweel, N., Friedrich, A., Schacherer, J., Aquadro, C. F., Alani, E.
shingle_author_2	Raghavan, V., Bui, D. T., Al-Sweel, N., Friedrich, A., Schacherer, J., Aquadro, C. F., Alani, E.
shingle_author_3	Raghavan, V., Bui, D. T., Al-Sweel, N., Friedrich, A., Schacherer, J., Aquadro, C. F., Alani, E.
shingle_author_4	Raghavan, V., Bui, D. T., Al-Sweel, N., Friedrich, A., Schacherer, J., Aquadro, C. F., Alani, E.
shingle_catch_all_1	Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Bakers Yeast [Genome Integrity and Transmission] Laboratory baker’s yeast strains bearing an incompatible combination of MLH1 and PMS1 mismatch repair alleles are mutators that can adapt more rapidly to stress, but do so at the cost of long-term fitness. We identified 18 baker’s yeast isolates from 1011 surveyed that contain the incompatible MLH1 - PMS1 genotype in a heterozygous state. Surprisingly, the incompatible combination from two human clinical heterozygous diploid isolates, YJS5845 and YJS5885, contain the exact MLH1 (S288c-derived) and PMS1 (SK1-derived) open reading frames originally shown to confer incompatibility. While these isolates were nonmutators, their meiotic spore clone progeny displayed mutation rates in a DNA slippage assay that varied over a 340-fold range. This range was 30-fold higher than observed between compatible and incompatible combinations of laboratory strains. Genotyping analysis indicated that MLH1 - PMS1 incompatibility was the major driver of mutation rate in the isolates. The variation in the mutation rate of incompatible spore clones could be due to background suppressors and enhancers, as well as aneuploidy seen in the spore clones. Our data are consistent with the observed variance in mutation rate contributing to adaptation to stress conditions ( e.g. , in a human host) through the acquisition of beneficial mutations, with high mutation rates leading to long-term fitness costs that are buffered by mating or eliminated through natural selection. Raghavan, V., Bui, D. T., Al-Sweel, N., Friedrich, A., Schacherer, J., Aquadro, C. F., Alani, E. Genetics Society of America (GSA) 0016-6731 00166731
shingle_catch_all_2	Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Bakers Yeast [Genome Integrity and Transmission] Laboratory baker’s yeast strains bearing an incompatible combination of MLH1 and PMS1 mismatch repair alleles are mutators that can adapt more rapidly to stress, but do so at the cost of long-term fitness. We identified 18 baker’s yeast isolates from 1011 surveyed that contain the incompatible MLH1 - PMS1 genotype in a heterozygous state. Surprisingly, the incompatible combination from two human clinical heterozygous diploid isolates, YJS5845 and YJS5885, contain the exact MLH1 (S288c-derived) and PMS1 (SK1-derived) open reading frames originally shown to confer incompatibility. While these isolates were nonmutators, their meiotic spore clone progeny displayed mutation rates in a DNA slippage assay that varied over a 340-fold range. This range was 30-fold higher than observed between compatible and incompatible combinations of laboratory strains. Genotyping analysis indicated that MLH1 - PMS1 incompatibility was the major driver of mutation rate in the isolates. The variation in the mutation rate of incompatible spore clones could be due to background suppressors and enhancers, as well as aneuploidy seen in the spore clones. Our data are consistent with the observed variance in mutation rate contributing to adaptation to stress conditions ( e.g. , in a human host) through the acquisition of beneficial mutations, with high mutation rates leading to long-term fitness costs that are buffered by mating or eliminated through natural selection. Raghavan, V., Bui, D. T., Al-Sweel, N., Friedrich, A., Schacherer, J., Aquadro, C. F., Alani, E. Genetics Society of America (GSA) 0016-6731 00166731
shingle_catch_all_3	Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Bakers Yeast [Genome Integrity and Transmission] Laboratory baker’s yeast strains bearing an incompatible combination of MLH1 and PMS1 mismatch repair alleles are mutators that can adapt more rapidly to stress, but do so at the cost of long-term fitness. We identified 18 baker’s yeast isolates from 1011 surveyed that contain the incompatible MLH1 - PMS1 genotype in a heterozygous state. Surprisingly, the incompatible combination from two human clinical heterozygous diploid isolates, YJS5845 and YJS5885, contain the exact MLH1 (S288c-derived) and PMS1 (SK1-derived) open reading frames originally shown to confer incompatibility. While these isolates were nonmutators, their meiotic spore clone progeny displayed mutation rates in a DNA slippage assay that varied over a 340-fold range. This range was 30-fold higher than observed between compatible and incompatible combinations of laboratory strains. Genotyping analysis indicated that MLH1 - PMS1 incompatibility was the major driver of mutation rate in the isolates. The variation in the mutation rate of incompatible spore clones could be due to background suppressors and enhancers, as well as aneuploidy seen in the spore clones. Our data are consistent with the observed variance in mutation rate contributing to adaptation to stress conditions ( e.g. , in a human host) through the acquisition of beneficial mutations, with high mutation rates leading to long-term fitness costs that are buffered by mating or eliminated through natural selection. Raghavan, V., Bui, D. T., Al-Sweel, N., Friedrich, A., Schacherer, J., Aquadro, C. F., Alani, E. Genetics Society of America (GSA) 0016-6731 00166731
shingle_catch_all_4	Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Bakers Yeast [Genome Integrity and Transmission] Laboratory baker’s yeast strains bearing an incompatible combination of MLH1 and PMS1 mismatch repair alleles are mutators that can adapt more rapidly to stress, but do so at the cost of long-term fitness. We identified 18 baker’s yeast isolates from 1011 surveyed that contain the incompatible MLH1 - PMS1 genotype in a heterozygous state. Surprisingly, the incompatible combination from two human clinical heterozygous diploid isolates, YJS5845 and YJS5885, contain the exact MLH1 (S288c-derived) and PMS1 (SK1-derived) open reading frames originally shown to confer incompatibility. While these isolates were nonmutators, their meiotic spore clone progeny displayed mutation rates in a DNA slippage assay that varied over a 340-fold range. This range was 30-fold higher than observed between compatible and incompatible combinations of laboratory strains. Genotyping analysis indicated that MLH1 - PMS1 incompatibility was the major driver of mutation rate in the isolates. The variation in the mutation rate of incompatible spore clones could be due to background suppressors and enhancers, as well as aneuploidy seen in the spore clones. Our data are consistent with the observed variance in mutation rate contributing to adaptation to stress conditions ( e.g. , in a human host) through the acquisition of beneficial mutations, with high mutation rates leading to long-term fitness costs that are buffered by mating or eliminated through natural selection. Raghavan, V., Bui, D. T., Al-Sweel, N., Friedrich, A., Schacherer, J., Aquadro, C. F., Alani, E. Genetics Society of America (GSA) 0016-6731 00166731
shingle_title_1	Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Bakers Yeast [Genome Integrity and Transmission]
shingle_title_2	Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Bakers Yeast [Genome Integrity and Transmission]
shingle_title_3	Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Bakers Yeast [Genome Integrity and Transmission]
shingle_title_4	Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Bakers Yeast [Genome Integrity and Transmission]
timestamp	2025-06-30T23:37:35.338Z
titel	Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Bakers Yeast [Genome Integrity and Transmission]
titel_suche	Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Bakers Yeast [Genome Integrity and Transmission]
topic	W
uid	ipn_articles_6365898