RT Journal Article
SR Electronic
T1 Mapping mutational effects along the evolutionary landscape of HIV envelope
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 235630
DO 10.1101/235630
A1 Haddox, Hugh K.
A1 Dingens, Adam S.
A1 Hilton, Sarah K.
A1 Overbaugh, Julie
A1 Bloom, Jesse D.
YR 2017
UL http://biorxiv.org/content/early/2017/12/16/235630.abstract
AB The immediate evolutionary space accessible to HIV is largely determined by how single amino-acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here we quantify the effects on viral growth of all amino-acid mutations to two HIV envelope (Env) proteins that differ at >100 residues. Most mutations similarly affect both Envs, but the amino-acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs -- and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env's mutational tolerance during HIV evolution, although the amino-acid preferences of most sites are conserved between moderately diverged viral strains.