Latent effects of Hsp90 mutants revealed at reduced expression levels.
In natural systems, selection acts on both protein sequence and expression level, but it is unclear how selection integrates over these two dimensions. We recently developed the EMPIRIC approach to systematically determine the fitness effects of all possible point mutants for important regions of es...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-06-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3694843?pdf=render |
| _version_ | 1818991375149957120 |
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| author | Li Jiang Parul Mishra Ryan T Hietpas Konstantin B Zeldovich Daniel N A Bolon |
| author_facet | Li Jiang Parul Mishra Ryan T Hietpas Konstantin B Zeldovich Daniel N A Bolon |
| author_sort | Li Jiang |
| collection | DOAJ |
| description | In natural systems, selection acts on both protein sequence and expression level, but it is unclear how selection integrates over these two dimensions. We recently developed the EMPIRIC approach to systematically determine the fitness effects of all possible point mutants for important regions of essential genes in yeast. Here, we systematically investigated the fitness effects of point mutations in a putative substrate binding loop of yeast Hsp90 (Hsp82) over a broad range of expression strengths. Negative epistasis between reduced expression strength and amino acid substitutions was common, and the endogenous expression strength frequently obscured mutant defects. By analyzing fitness effects at varied expression strengths, we were able to uncover all mutant effects on function. The majority of mutants caused partial functional defects, consistent with this region of Hsp90 contributing to a mutation sensitive and critical process. These results demonstrate that important functional regions of proteins can tolerate mutational defects without experimentally observable impacts on fitness. |
| first_indexed | 2024-12-20T20:09:16Z |
| format | Article |
| id | doaj.art-c0b6ef4ded4f436894a5a0aecde6d9b0 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-20T20:09:16Z |
| publishDate | 2013-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-c0b6ef4ded4f436894a5a0aecde6d9b02022-12-21T19:27:51ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-06-0196e100360010.1371/journal.pgen.1003600Latent effects of Hsp90 mutants revealed at reduced expression levels.Li JiangParul MishraRyan T HietpasKonstantin B ZeldovichDaniel N A BolonIn natural systems, selection acts on both protein sequence and expression level, but it is unclear how selection integrates over these two dimensions. We recently developed the EMPIRIC approach to systematically determine the fitness effects of all possible point mutants for important regions of essential genes in yeast. Here, we systematically investigated the fitness effects of point mutations in a putative substrate binding loop of yeast Hsp90 (Hsp82) over a broad range of expression strengths. Negative epistasis between reduced expression strength and amino acid substitutions was common, and the endogenous expression strength frequently obscured mutant defects. By analyzing fitness effects at varied expression strengths, we were able to uncover all mutant effects on function. The majority of mutants caused partial functional defects, consistent with this region of Hsp90 contributing to a mutation sensitive and critical process. These results demonstrate that important functional regions of proteins can tolerate mutational defects without experimentally observable impacts on fitness.http://europepmc.org/articles/PMC3694843?pdf=render |
| spellingShingle | Li Jiang Parul Mishra Ryan T Hietpas Konstantin B Zeldovich Daniel N A Bolon Latent effects of Hsp90 mutants revealed at reduced expression levels. PLoS Genetics |
| title | Latent effects of Hsp90 mutants revealed at reduced expression levels. |
| title_full | Latent effects of Hsp90 mutants revealed at reduced expression levels. |
| title_fullStr | Latent effects of Hsp90 mutants revealed at reduced expression levels. |
| title_full_unstemmed | Latent effects of Hsp90 mutants revealed at reduced expression levels. |
| title_short | Latent effects of Hsp90 mutants revealed at reduced expression levels. |
| title_sort | latent effects of hsp90 mutants revealed at reduced expression levels |
| url | http://europepmc.org/articles/PMC3694843?pdf=render |
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