RT Journal Article
SR Electronic
T1 Within-patient HIV mutation frequencies reveal fitness costs of CpG dinucleotides, drastic amino acid changes and G→A mutations
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 057026
DO 10.1101/057026
A1 Marion Hartl
A1 Kristof Theys
A1 Alison Feder
A1 Maoz Gelbart
A1 Adi Stern
A1 Pleuni S. Pennings
YR 2016
UL http://biorxiv.org/content/early/2016/06/03/057026.abstract
AB HIV has a high mutation rate and exhibits remarkable genetic diversity. However, we know little about the fitness cost of HIV mutations in vivo. We calculated the mean frequency of mutations at 870 sites of the pol gene in 160 patients, allowing us to determine the cost of different types of mutations. We found that non-synonymous mutations that lead to drastic amino acid changes are three times more costly than those that do not, mutations that create new CpG dinucleotides are up to four times more costly than those that do not, and G→A mutations are more than twice as costly as A→G mutations. In addition, within-patient mutation frequencies are highly correlated with substitution frequencies across the global HIV pandemic. We anticipate our new frequency-based approach will provide insights into the fitness landscape and evolvability of not only HIV, but a variety of microbes.