Exploring a Local Genetic Interaction Network Using Evolutionary Replay Experiments
| Autor: | Gregory I. Lang, Ryan C. Vignogna, Sean W. Buskirk |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
genetic interactions
Population Saccharomyces cerevisiae Computational biology yeast AcademicSubjects/SCI01180 medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Genetics medicine Gene Regulatory Networks experimental evolution Selection Genetic education Molecular Biology Gene Discoveries Ecology Evolution Behavior and Systematics Allele specific 030304 developmental biology 0303 health sciences education.field_of_study Experimental evolution Mutation Genetic interaction Models Genetic biology AcademicSubjects/SCI01130 Gene deletion biology.organism_classification Biological Evolution Yeast Mutation (genetic algorithm) 030217 neurology & neurosurgery |
| Zdroj: | Molecular Biology and Evolution |
| ISSN: | 1537-1719 |
| Popis: | Understanding how genes interact is a central challenge in biology. Experimental evolution provides a useful, but underutilized, tool for identifying genetic interactions, particularly those that involve non-loss-of-function mutations or mutations in essential genes. We previously identified a strong positive genetic interaction between specific mutations in KEL1 (P344T) and HSL7 (A695fs) that arose in an experimentally-evolved Saccharomyces cerevisiae population. Because this genetic interaction is not phenocopied by gene deletion, it was previously unknown. Using “evolutionary replay” experiments we identified additional mutations that have positive genetic interactions with the kel1-P344T mutation. We replayed the evolution of this population 672 times from six timepoints. We identified 30 populations where the kel1-P344T mutation reached high frequency. We performed whole-genome sequencing on these populations to identify genes in which mutations arose specifically in the kel1-P344T background. We reconstructed mutations in the ancestral and kel1-P344T backgrounds to validate positive genetic interactions. We identify several genetic interactors with KEL1, we validate these interactions by reconstruction experiments, and we show these interactions are not recapitulated by loss-of-function mutations. Our results demonstrate the power of experimental evolution to identify genetic interactions that are positive, allele specific, and not readily detected by other methods, and sheds light on a previously under-explored region of the yeast genetic interaction network. |
| Databáze: | OpenAIRE |
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