Contrasting properties of gene-specific regulatory, coding, and copy number mutations in Saccharomyces cerevisiae: frequency, effects, and dominance.
Genetic variation within and between species can be shaped by population-level processes and mutation; however, the relative impact of "survival of the fittest" and "arrival of the fittest" on phenotypic evolution remains unclear. Assessing the influence of mutation on evolution...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-02-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3276545?pdf=render |
| _version_ | 1819238560811712512 |
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| author | Jonathan D Gruber Kara Vogel Gizem Kalay Patricia J Wittkopp |
| author_facet | Jonathan D Gruber Kara Vogel Gizem Kalay Patricia J Wittkopp |
| author_sort | Jonathan D Gruber |
| collection | DOAJ |
| description | Genetic variation within and between species can be shaped by population-level processes and mutation; however, the relative impact of "survival of the fittest" and "arrival of the fittest" on phenotypic evolution remains unclear. Assessing the influence of mutation on evolution requires understanding the relative rates of different types of mutations and their genetic properties, yet little is known about the functional consequences of new mutations. Here, we examine the spectrum of mutations affecting a focal gene in Saccharomyces cerevisiae by characterizing 231 novel haploid genotypes with altered activity of a fluorescent reporter gene. 7% of these genotypes had a nonsynonymous mutation in the coding sequence for the fluorescent protein and were classified as "coding" mutants; 2% had a change in the S. cerevisiae TDH3 promoter sequence controlling expression of the fluorescent protein and were classified as "cis-regulatory" mutants; 10% contained two copies of the reporter gene and were classified as "copy number" mutants; and the remaining 81% showed altered fluorescence without a change in the reporter gene itself and were classified as "trans-acting" mutants. As a group, coding mutants had the strongest effect on reporter gene activity and always decreased it. By contrast, 50%-95% of the mutants in each of the other three classes increased gene activity, with mutants affecting copy number and cis-regulatory sequences having larger median effects on gene activity than trans-acting mutants. When made heterozygous in diploid cells, coding, cis-regulatory, and copy number mutant genotypes all had significant effects on gene activity, whereas 88% of the trans-acting mutants appeared to be recessive. These differences in the frequency, effects, and dominance among functional classes of mutations might help explain why some types of mutations are found to be segregating within or fixed between species more often than others. |
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| format | Article |
| id | doaj.art-ab104ef7c4d244a69d1e64def10c4f89 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-23T13:38:10Z |
| publishDate | 2012-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-ab104ef7c4d244a69d1e64def10c4f892022-12-21T17:44:58ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-02-0182e100249710.1371/journal.pgen.1002497Contrasting properties of gene-specific regulatory, coding, and copy number mutations in Saccharomyces cerevisiae: frequency, effects, and dominance.Jonathan D GruberKara VogelGizem KalayPatricia J WittkoppGenetic variation within and between species can be shaped by population-level processes and mutation; however, the relative impact of "survival of the fittest" and "arrival of the fittest" on phenotypic evolution remains unclear. Assessing the influence of mutation on evolution requires understanding the relative rates of different types of mutations and their genetic properties, yet little is known about the functional consequences of new mutations. Here, we examine the spectrum of mutations affecting a focal gene in Saccharomyces cerevisiae by characterizing 231 novel haploid genotypes with altered activity of a fluorescent reporter gene. 7% of these genotypes had a nonsynonymous mutation in the coding sequence for the fluorescent protein and were classified as "coding" mutants; 2% had a change in the S. cerevisiae TDH3 promoter sequence controlling expression of the fluorescent protein and were classified as "cis-regulatory" mutants; 10% contained two copies of the reporter gene and were classified as "copy number" mutants; and the remaining 81% showed altered fluorescence without a change in the reporter gene itself and were classified as "trans-acting" mutants. As a group, coding mutants had the strongest effect on reporter gene activity and always decreased it. By contrast, 50%-95% of the mutants in each of the other three classes increased gene activity, with mutants affecting copy number and cis-regulatory sequences having larger median effects on gene activity than trans-acting mutants. When made heterozygous in diploid cells, coding, cis-regulatory, and copy number mutant genotypes all had significant effects on gene activity, whereas 88% of the trans-acting mutants appeared to be recessive. These differences in the frequency, effects, and dominance among functional classes of mutations might help explain why some types of mutations are found to be segregating within or fixed between species more often than others.http://europepmc.org/articles/PMC3276545?pdf=render |
| spellingShingle | Jonathan D Gruber Kara Vogel Gizem Kalay Patricia J Wittkopp Contrasting properties of gene-specific regulatory, coding, and copy number mutations in Saccharomyces cerevisiae: frequency, effects, and dominance. PLoS Genetics |
| title | Contrasting properties of gene-specific regulatory, coding, and copy number mutations in Saccharomyces cerevisiae: frequency, effects, and dominance. |
| title_full | Contrasting properties of gene-specific regulatory, coding, and copy number mutations in Saccharomyces cerevisiae: frequency, effects, and dominance. |
| title_fullStr | Contrasting properties of gene-specific regulatory, coding, and copy number mutations in Saccharomyces cerevisiae: frequency, effects, and dominance. |
| title_full_unstemmed | Contrasting properties of gene-specific regulatory, coding, and copy number mutations in Saccharomyces cerevisiae: frequency, effects, and dominance. |
| title_short | Contrasting properties of gene-specific regulatory, coding, and copy number mutations in Saccharomyces cerevisiae: frequency, effects, and dominance. |
| title_sort | contrasting properties of gene specific regulatory coding and copy number mutations in saccharomyces cerevisiae frequency effects and dominance |
| url | http://europepmc.org/articles/PMC3276545?pdf=render |
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