University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Publication Date
2017-05-17
Document Type
Article Preprint
Disciplines
Amino Acids, Peptides, and Proteins | Bioinformatics | Ecology and Evolutionary Biology | Genetic Phenomena
Abstract
Although the primary protein sequence of ubiquitin (Ub) is extremely stable over evolutionary time, it is highly tolerant to mutation during selection experiments performed in the laboratory. We have proposed that this discrepancy results from the difference between fitness under laboratory culture conditions and the selective pressures in changing environments over evolutionary time scales. Building on our previous work (Mavor et al. 2016), we used deep mutational scanning to determine how twelve new chemicals reveal novel mutational sensitivities of ubiquitin residues. We found sensitization of Lys63 in eight new conditions. In total, our experiments have uncovered a highly sensitizing condition for every position in Ub except Ser57 and Gln62. By determining the Ubiquitin fitness landscape under different chemical constraints, our work helps to resolve the inconsistencies between deep mutational scanning experiments and sequence conservation over evolutionary timescales.
Keywords
bioinformatics, Ubiquitin, mutation, deep mutational scanning, evolution
Rights and Permissions
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY 4.0 International license.
DOI of Published Version
10.1101/139352
Source
bioRxiv 139352; doi: https://doi.org/10.1101/139352. Link to preprint on bioRxiv service.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Mavor, David; Bolon, Daniel N.; Kampmann, Martin; and Fraser, James S., "Extending Chemical Perturbations Of The Ubiquitin Fitness Landscape In A Classroom Setting" (2017). University of Massachusetts Medical School Faculty Publications. 1541.
https://escholarship.umassmed.edu/faculty_pubs/1541
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Amino Acids, Peptides, and Proteins Commons, Bioinformatics Commons, Ecology and Evolutionary Biology Commons, Genetic Phenomena Commons
Comments
Full author list omitted for brevity. For the full list of authors, see article.