The strength of genetic interactions scales weakly with mutational effects
Background: Genetic interactions pervade every aspect of biology, from evolutionary theory, where they determine the accessibility of evolutionary paths, to medicine, where they can contribute to complex genetic diseases. Until very recently, studies on epistatic interactions have been based on a h...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
BioMed Central Ltd
2013
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| Online Access: | http://hdl.handle.net/1721.1/81971 https://orcid.org/0000-0003-4583-8555 |
| _version_ | 1826192509068378112 |
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| author | Velenich, Andrea Gore, Jeff |
| author2 | Massachusetts Institute of Technology. Department of Physics |
| author_facet | Massachusetts Institute of Technology. Department of Physics Velenich, Andrea Gore, Jeff |
| author_sort | Velenich, Andrea |
| collection | MIT |
| description | Background:
Genetic interactions pervade every aspect of biology, from evolutionary theory, where they determine the accessibility of evolutionary paths, to medicine, where they can contribute to complex genetic diseases. Until very recently, studies on epistatic interactions have been based on a handful of mutations, providing at best anecdotal evidence about the frequency and the typical strength of genetic interactions. In this study, we analyze a publicly available dataset that contains the growth rates of over five million double knockout mutants of the yeast Saccharomyces cerevisiae.
Results:
We discuss a geometric definition of epistasis that reveals a simple and surprisingly weak scaling law for the characteristic strength of genetic interactions as a function of the effects of the mutations being combined. We then utilized this scaling to quantify the roughness of naturally occurring fitness landscapes. Finally, we show how the observed roughness differs from what is predicted by Fisher's geometric model of epistasis, and discuss the consequences for evolutionary dynamics.
Conclusions:
Although epistatic interactions between specific genes remain largely unpredictable, the statistical properties of an ensemble of interactions can display conspicuous regularities and be described by simple mathematical laws. By exploiting the amount of data produced by modern high-throughput techniques, it is now possible to thoroughly test the predictions of theoretical models of genetic interactions and to build informed computational models of evolution on realistic fitness landscapes. |
| first_indexed | 2024-09-23T09:17:44Z |
| format | Article |
| id | mit-1721.1/81971 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:17:44Z |
| publishDate | 2013 |
| publisher | BioMed Central Ltd |
| record_format | dspace |
| spelling | mit-1721.1/819712022-09-30T14:10:20Z The strength of genetic interactions scales weakly with mutational effects Velenich, Andrea Gore, Jeff Massachusetts Institute of Technology. Department of Physics Velenich, Andrea Gore, Jeff Background: Genetic interactions pervade every aspect of biology, from evolutionary theory, where they determine the accessibility of evolutionary paths, to medicine, where they can contribute to complex genetic diseases. Until very recently, studies on epistatic interactions have been based on a handful of mutations, providing at best anecdotal evidence about the frequency and the typical strength of genetic interactions. In this study, we analyze a publicly available dataset that contains the growth rates of over five million double knockout mutants of the yeast Saccharomyces cerevisiae. Results: We discuss a geometric definition of epistasis that reveals a simple and surprisingly weak scaling law for the characteristic strength of genetic interactions as a function of the effects of the mutations being combined. We then utilized this scaling to quantify the roughness of naturally occurring fitness landscapes. Finally, we show how the observed roughness differs from what is predicted by Fisher's geometric model of epistasis, and discuss the consequences for evolutionary dynamics. Conclusions: Although epistatic interactions between specific genes remain largely unpredictable, the statistical properties of an ensemble of interactions can display conspicuous regularities and be described by simple mathematical laws. By exploiting the amount of data produced by modern high-throughput techniques, it is now possible to thoroughly test the predictions of theoretical models of genetic interactions and to build informed computational models of evolution on realistic fitness landscapes. National Institutes of Health (U.S.) (Pathways to Independence Award) National Science Foundation (U.S.) (CAREER Award) Pew Charitable Trusts (Biomedical Scholars Program) Alfred P. Sloan Foundation (Research Fellowship) 2013-11-04T16:29:39Z 2013-11-04T16:29:39Z 2013-07 2013-07 2013-11-04T12:11:44Z Article http://purl.org/eprint/type/JournalArticle 1465-6906 1474-7596 http://hdl.handle.net/1721.1/81971 Velenich, Andrea, and Jeff Gore. “The Strength of Genetic Interactions Scales Weakly with Mutational Effects.” Genome Biology 14.7 (2013): R76. https://orcid.org/0000-0003-4583-8555 en http://dx.doi.org/10.1186/gb-2013-14-7-r76 Genome Biology Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 Andrea Velenich et al.; licensee BioMed Central Ltd. application/pdf BioMed Central Ltd BioMed Central Ltd |
| spellingShingle | Velenich, Andrea Gore, Jeff The strength of genetic interactions scales weakly with mutational effects |
| title | The strength of genetic interactions scales weakly with mutational effects |
| title_full | The strength of genetic interactions scales weakly with mutational effects |
| title_fullStr | The strength of genetic interactions scales weakly with mutational effects |
| title_full_unstemmed | The strength of genetic interactions scales weakly with mutational effects |
| title_short | The strength of genetic interactions scales weakly with mutational effects |
| title_sort | strength of genetic interactions scales weakly with mutational effects |
| url | http://hdl.handle.net/1721.1/81971 https://orcid.org/0000-0003-4583-8555 |
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