In-vivo mutation rates and fitness landscape of HIV-1
| Autor: | Richard A. Neher, Johanna Brodin, Jan Albert, Vadim Puller, Fabio Zanini |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Genetics
0303 health sciences Mutation rate Genetic diversity Saturation (genetic) Fitness landscape Populations and Evolution (q-bio.PE) Biology Genome 3. Good health 03 medical and health sciences 0302 clinical medicine FOS: Biological sciences Genetic variation Quantitative Biology - Populations and Evolution Synonymous substitution Gene 030304 developmental biology 030215 immunology |
| DOI: | 10.1101/045039 |
| Popis: | Mutation rates and fitness costs of deleterious mutations are difficult to measurein vivobut essential for a quantitative understanding of evolution. Using whole genome deep sequencing data from longitudinal samples during untreated HIV-1 infection, we estimated mutation rates and fitness costs in HIV-1 from the temporal dynamics of genetic variation. At approximately neutral sites, mutations accumulate with a rate of 1.2 x 10-5per site per day, in agreement with the rate measured in cell cultures. The rate from G to A is largest, followed by the other transitions C to T, T to C, and A to G, while transversions are more rare. At non-neutral sites, most mutations reduce virus replication; using a model of mutation selection balance, we estimated the fitness cost of mutations at every site in the HIV-1 genome. About half of all nonsynonymous mutations have large fitness costs (greater than 10%), while most synonymous mutations have costs below 1%. The cost of synonymous mutations is especially low in most of gag and pol, while much higher costs are observed in important RNA structures and regulatory regions. The intrapatient fitness cost estimates are consistent across multiple patients, suggesting that the deleterious part of the fitness landscape is universal and explains a large fraction of global HIV-1 group M diversity. |
| Databáze: | OpenAIRE |
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