ArticleGenetics2010
Fitness epistasis and constraints on adaptation in a human immunodeficiency virus type 1 protein region.
Article in Genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- Detecting fitness epistasis in recently admixed populations with genome-wide data.BMC genomics · 2020Pooled it
- Comparison of allele frequencies of Plasmodium falciparum merozoite antigens in malaria infections sampled in different years in a Kenyan population.Malaria journal · 2016Trial
- Deconstructing empirical fitness seascapes across scales of granularity.G3 (Bethesda, Md.) · 2026Article
- Deconstructing empirical fitness seascapes across scales of granularity.bioRxiv : the preprint server for biology · 2026Article
- The importance of epistasis in the evolution of viral pathogens.Virus evolution · 2025Review
- Patterns of Fitness and Gene Expression Epistasis Generated by Beneficial Mutations in the rho and rpoB Genes of Escherichia coli during High-Temperature Adaptation.Molecular biology and evolution · 2024Article
- Changing selection on amino acid substitutions in Gag protein between major HIV-1 subtypes.Virus evolution · 2024Article
- Paired associated SARS-CoV-2 spike variable positions: a network analysis approach to emerging variants.mSystems · 2023Article
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- A tractable physical model for the yeast polarity predicts epistasis and fitness.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Genetic complementation fosters evolvability in complex fitness landscapes.Scientific reports · 2023Article
- Intragenic compensation through the lens of deep mutational scanning.Biophysical reviews · 2022Review
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- Article
- Article
- Evolution in alternating environments with tunable interlandscape correlations.Evolution; international journal of organic evolution · 2021Article
- Long-term experimental evolution of HIV-1 reveals effects of environment and mutational history.PLoS biology · 2020Article
- Site-Specific Evolutionary Rate Shifts in HIV-1 and SIV.Viruses · 2020Article
- Inferring a complete genotype-phenotype map from a small number of measured phenotypes.PLoS computational biology · 2020Article
- Model genotype-phenotype mappings and the algorithmic structure of evolution.Journal of the Royal Society, Interface · 2019Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Fitness epistasis, the interaction among alleles at different loci in their effects on fitness, has potentially important consequences for adaptive evolution. We investigated fitness epistasis among amino acids of a functionally important region of the human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein (gp120). Seven mutations putatively involved in the adaptation of the second conserved to third variable protein region (C2-V3) to the use of an alternative host-cell chemokine coreceptor (CXCR4) for cell entry were engineered singly and in combinations on the wild-type genetic background and their effects on viral infectivity were measured. Epistasis was found to be common and complex, involving not only pairwise interactions, but also higher-order interactions. Interactions could also be surprisingly strong, changing fitness by more than 9 orders of magnitude, which is explained by some single mutations being practically lethal. A consequence of the observed epistasis is that many of the minimum-length mutational trajectories between the wild type and the mutant with highest fitness on cells expressing the alternative coreceptor are selectively inaccessible. These results may help explain the difficulty of evolving viruses that use the alternative coreceptor in culture and the delayed evolution of this phenotype in natural infection. Knowledge of common, complex, and strong fitness interactions among amino acids is necessary for a full understanding of protein evolution.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.