More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1
In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations ari...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/10670 |
| _version_ | 1818019172286726144 |
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| author | Alison F Feder Soo-Yon Rhee Susan P Holmes Robert W Shafer Dmitri A Petrov Pleuni S Pennings |
| author_facet | Alison F Feder Soo-Yon Rhee Susan P Holmes Robert W Shafer Dmitri A Petrov Pleuni S Pennings |
| author_sort | Alison F Feder |
| collection | DOAJ |
| description | In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here, we use 6717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely. |
| first_indexed | 2024-04-14T07:48:47Z |
| format | Article |
| id | doaj.art-5458245ada0f46a3b6e0a43f08a63d28 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:48:47Z |
| publishDate | 2016-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5458245ada0f46a3b6e0a43f08a63d282022-12-22T02:05:15ZengeLife Sciences Publications LtdeLife2050-084X2016-02-01510.7554/eLife.10670More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1Alison F Feder0Soo-Yon Rhee1Susan P Holmes2Robert W Shafer3Dmitri A Petrov4Pleuni S Pennings5Department of Biology, Stanford University, Stanford, United StatesDepartment of Medicine, Stanford University, Stanford, United StatesDepartment of Statistics, Stanford University, Stanford, United StatesDepartment of Medicine, Stanford University, Stanford, United StatesDepartment of Biology, Stanford University, Stanford, United StatesDepartment of Biology, Stanford University, Stanford, United States; Department of Biology, San Francisco State University, San Francisco, United StatesIn the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here, we use 6717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely.https://elifesciences.org/articles/10670HIVSoft SweepsDrug ResistanceWithin-host evolutionaryEvolutionary Dynamics |
| spellingShingle | Alison F Feder Soo-Yon Rhee Susan P Holmes Robert W Shafer Dmitri A Petrov Pleuni S Pennings More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1 eLife HIV Soft Sweeps Drug Resistance Within-host evolutionary Evolutionary Dynamics |
| title | More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1 |
| title_full | More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1 |
| title_fullStr | More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1 |
| title_full_unstemmed | More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1 |
| title_short | More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1 |
| title_sort | more effective drugs lead to harder selective sweeps in the evolution of drug resistance in hiv 1 |
| topic | HIV Soft Sweeps Drug Resistance Within-host evolutionary Evolutionary Dynamics |
| url | https://elifesciences.org/articles/10670 |
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