Stochasticity in the genotype-phenotype map: Implications for the robustness and persistence of bet-hedging
Non–genetic variation in phenotypes, or bet–hedging, has been observed as a driver of drug resistance in both bacterial infections and cancers. Here, we study how bet–hedging emerges in the genotype–phenotype mapping through a simple mechanistic model: a molecular switch. By using model Chemical Rea...
| Váldodahkkit: | , , , |
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| Materiálatiipa: | Journal article |
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Genetics Society of America
2016
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| _version_ | 1826287838946131968 |
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| author | Nichol, D Robertson-Tessi, M Jeavons, P Anderson, A |
| author_facet | Nichol, D Robertson-Tessi, M Jeavons, P Anderson, A |
| author_sort | Nichol, D |
| collection | OXFORD |
| description | Non–genetic variation in phenotypes, or bet–hedging, has been observed as a driver of drug resistance in both bacterial infections and cancers. Here, we study how bet–hedging emerges in the genotype–phenotype mapping through a simple mechanistic model: a molecular switch. By using model Chemical Reaction Networks to implement a stochastic switch that maps gene products to phenotypes, we investigate the impact of structurally distinct mappings on the evolution of phenotypic heterogeneity. Bet–hedging naturally emerges within this model and is robust to evolutionary loss through mutations to both the expression of individual genes and to the network itself. This robustness explains an apparent paradox of bet–hedging – why does it persist in environments where natural selection necessarily acts to remove it? The structure of the underlying molecular mechanism, itself subject to selection, can slow the evolutionary loss of bet–hedging to ensure a survival mechanism against environmental catastrophes even when they are rare. Critically, these properties taken together have profound implications for the use of treatment–holidays to combat bet–hedging–driven resistant disease, as the efficacy of breaks from treatment will ultimately be determined by the structure of the genotype–phenotype mapping. |
| first_indexed | 2024-03-07T02:04:40Z |
| format | Journal article |
| id | oxford-uuid:9e8f8788-8c86-4ff5-8d2e-c093d0d89821 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T02:04:40Z |
| publishDate | 2016 |
| publisher | Genetics Society of America |
| record_format | dspace |
| spelling | oxford-uuid:9e8f8788-8c86-4ff5-8d2e-c093d0d898212022-03-27T00:51:01ZStochasticity in the genotype-phenotype map: Implications for the robustness and persistence of bet-hedgingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9e8f8788-8c86-4ff5-8d2e-c093d0d89821Symplectic Elements at OxfordGenetics Society of America2016Nichol, DRobertson-Tessi, MJeavons, PAnderson, ANon–genetic variation in phenotypes, or bet–hedging, has been observed as a driver of drug resistance in both bacterial infections and cancers. Here, we study how bet–hedging emerges in the genotype–phenotype mapping through a simple mechanistic model: a molecular switch. By using model Chemical Reaction Networks to implement a stochastic switch that maps gene products to phenotypes, we investigate the impact of structurally distinct mappings on the evolution of phenotypic heterogeneity. Bet–hedging naturally emerges within this model and is robust to evolutionary loss through mutations to both the expression of individual genes and to the network itself. This robustness explains an apparent paradox of bet–hedging – why does it persist in environments where natural selection necessarily acts to remove it? The structure of the underlying molecular mechanism, itself subject to selection, can slow the evolutionary loss of bet–hedging to ensure a survival mechanism against environmental catastrophes even when they are rare. Critically, these properties taken together have profound implications for the use of treatment–holidays to combat bet–hedging–driven resistant disease, as the efficacy of breaks from treatment will ultimately be determined by the structure of the genotype–phenotype mapping. |
| spellingShingle | Nichol, D Robertson-Tessi, M Jeavons, P Anderson, A Stochasticity in the genotype-phenotype map: Implications for the robustness and persistence of bet-hedging |
| title | Stochasticity in the genotype-phenotype map: Implications for the robustness and persistence of bet-hedging |
| title_full | Stochasticity in the genotype-phenotype map: Implications for the robustness and persistence of bet-hedging |
| title_fullStr | Stochasticity in the genotype-phenotype map: Implications for the robustness and persistence of bet-hedging |
| title_full_unstemmed | Stochasticity in the genotype-phenotype map: Implications for the robustness and persistence of bet-hedging |
| title_short | Stochasticity in the genotype-phenotype map: Implications for the robustness and persistence of bet-hedging |
| title_sort | stochasticity in the genotype phenotype map implications for the robustness and persistence of bet hedging |
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