ArticlePLoS genetics2014
Epistatically interacting substitutions are enriched during adaptive protein evolution.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 71 citations in OpenAlex.
- Recombinant inbred line panels inform the genetic architecture and interactions of adaptive traits in Drosophila melanogaster.G3 (Bethesda, Md.) · 2025Article
- Protein Quality Control is a Master Modulator of Molecular Evolution in Bacteria.Genome biology and evolution · 2025Review
- Article
- Experimental andACS infectious diseases · 2022Article
- Epistatic Effects Between Amino Acid Insertions and Substitutions Mediate Toxin resistance of Vertebrate Na+,K+-ATPases.Molecular biology and evolution · 2022Article
- Intragenic compensation through the lens of deep mutational scanning.Biophysical reviews · 2022Review
- Article
- Article
- Adaptive Landscapes in the Age of Synthetic Biology.Molecular biology and evolution · 2019Review
- An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape.PLoS genetics · 2019Article
- Article
- The evolution of seasonal influenza viruses.Nature reviews. Microbiology · 2018Review
- Sequence entropy of folding and the absolute rate of amino acid substitutions.Nature ecology & evolution · 2017Article
- Selection on non-antigenic gene segments of seasonal influenza A virus and its impact on adaptive evolution.Virus evolution · 2017Article
- Single-mutation fitness landscapes for an enzyme on multiple substrates reveal specificity is globally encoded.Nature communications · 2017Article
- Experimental Evolution of Escherichia coli Harboring an Ancient Translation Protein.Journal of molecular evolution · 2017Article
- The effective rate of influenza reassortment is limited during human infection.PLoS pathogens · 2017Article
- Detecting Adaptation in Protein-Coding Genes Using a Bayesian Site-Heterogeneous Mutation-Selection Codon Substitution Model.Molecular biology and evolution · 2017Article
- Article
- Long-term adaptation of the influenza A virus by escaping cytotoxic T-cell recognition.Scientific reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Most experimental studies of epistasis in evolution have focused on adaptive changes-but adaptation accounts for only a portion of total evolutionary change. Are the patterns of epistasis during adaptation representative of evolution more broadly? We address this question by examining a pair of protein homologs, of which only one is subject to a well-defined pressure for adaptive change. Specifically, we compare the nucleoproteins from human and swine influenza. Human influenza is under continual selection to evade recognition by acquired immune memory, while swine influenza experiences less such selection due to the fact that pigs are less likely to be infected with influenza repeatedly in a lifetime. Mutations in some types of immune epitopes are therefore much more strongly adaptive to human than swine influenza--here we focus on epitopes targeted by human cytotoxic T lymphocytes. The nucleoproteins of human and swine influenza possess nearly identical numbers of such epitopes. However, mutations in these epitopes are fixed significantly more frequently in human than in swine influenza, presumably because these epitope mutations are adaptive only to human influenza. Experimentally, we find that epistatically constrained mutations are fixed only in the adaptively evolving human influenza lineage, where they occur at sites that are enriched in epitopes. Overall, our results demonstrate that epistatically interacting substitutions are enriched during adaptation, suggesting that the prevalence of epistasis is dependent on the underlying evolutionary forces at play.
Indexed as
Identifiers
What OpenQuestion holds
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.