RT Journal Article
SR Electronic
T1 In-vivo mutation rates and fitness landscape of HIV-1
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 045039
DO 10.1101/045039
A1 Fabio Zanini
A1 Vadim Puller
A1 Johanna Brodin
A1 Jan Albert
A1 Richard A. Neher
YR 2016
UL http://biorxiv.org/content/early/2016/03/21/045039.abstract
AB Mutation rates and fitness costs of deleterious mutations are difficult to measure in vivo but essential for a quantitative understanding of of evolution. Using whole genome deep sequencing data on longitudinal samples during untreated HIV-1 infection, we estimated mutation rates and the distribution of fitness costs in HIV-1 from the temporal dynamics of genetic variation. At approximately neutral sites, mutations accumulate with rates similar to those measured in cell cultures. Genetic diversity at other sites saturates and we estimated the fitness costs at those sites from the time and level of saturation. About half of all non-synonymous mutations have fitness costs greater than 10%, while half of synonymous mutations have costs below 1% such that they are essentially neutral over the course of a year. Fitness costs of mutations that are synonymous in one gene but affect proteins in other reading frame or important RNA structures are distributed similarly to non-synonymous mutations. Within patient fitness landscape explains a large fraction of global HIV-1 group M diversity.