Mapping mutational effects along the evolutionary landscape of HIV envelope
- Fred Hutchinson Cancer Research Center, United States
Abstract
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.
Data availability
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Deep mutational scanning of BF520Publicly available at the NCBI SAMN06313000.
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Deep mutational scanning of BG505Publicly available at the NCBI SAMN07718028.
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Computer codehttps://github.com/jbloomlab/EnvMutationalShiftsPaper.
Article and author information
Author details
Funding
National Institutes of Health (R01-AI127893)
- Jesse D Bloom
National Science Foundation (DGE-1256082)
- Adam S Dingens
Howard Hughes Medical Institute (Faculty Scholar Grant)
- Jesse D Bloom
Simons Foundation (Faculty Scholar Grant)
- Jesse D Bloom
Collaboration for AIDS Vaccine Discovery (OPP1111923)
- Jesse D Bloom
National Institutes of Health (DP1-DA039543)
- Julie Overbaugh
National Institutes of Health (T32GM007270)
- Hugh K Haddox
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Arup K Chakraborty, Massachusetts Institute of Technology, United States
Version history
- Received: December 17, 2017
- Accepted: March 15, 2018
- Accepted Manuscript published: March 28, 2018 (version 1)
- Version of Record published: April 20, 2018 (version 2)
- Version of Record updated: May 8, 2018 (version 3)
Copyright
© 2018, Haddox et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mapping mutational effects along the evolutionary landscape of HIV envelope
eLife 7:e34420.
https://doi.org/10.7554/eLife.34420
Further reading
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- Biochemistry and Chemical Biology
- Evolutionary Biology
The emergence of new protein functions is crucial for the evolution of organisms. This process has been extensively researched for soluble enzymes, but it is largely unexplored for membrane transporters, even though the ability to acquire new nutrients from a changing environment requires evolvability of transport functions. Here, we demonstrate the importance of environmental pressure in obtaining a new activity or altering a promiscuous activity in members of the amino acid-polyamine-organocation (APC)-type yeast amino acid transporters family. We identify APC members that have broader substrate spectra than previously described. Using in vivo experimental evolution, we evolve two of these transporter genes, AGP1 and PUT4, toward new substrate specificities. Single mutations on these transporters are found to be sufficient for expanding the substrate range of the proteins, while retaining the capacity to transport all original substrates. Nonetheless, each adaptive mutation comes with a distinct effect on the fitness for each of the original substrates, illustrating a trade-off between the ancestral and evolved functions. Collectively, our findings reveal how substrate-adaptive mutations in membrane transporters contribute to fitness and provide insights into how organisms can use transporter evolution to explore new ecological niches.
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