Rxivist logo

In-vivo mutation rates and fitness landscape of HIV-1

By Fabio Zanini, Vadim Puller, Johanna Brodin, Jan Albert, Richard A. Neher

Posted 21 Mar 2016
bioRxiv DOI: 10.1101/045039 (published DOI: 10.1093/ve/vex003)

Mutation rates and fitness costs of deleterious mutations are difficult to measure in vivo but 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 10-5 per 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.

Download data

  • Downloaded 854 times
  • Download rankings, all-time:
    • Site-wide: 17,848 out of 106,159
    • In evolutionary biology: 1,034 out of 6,128
  • Year to date:
    • Site-wide: 74,042 out of 106,159
  • Since beginning of last month:
    • Site-wide: 73,232 out of 106,159

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News