ReviewProtein science : a publication of the Protein Society2016
Quantifying and understanding the fitness effects of protein mutations: Laboratory versus nature.
Review in Protein science : a publication of the Protein Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 51 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
51 citing papers in PubMed.
- Uncovering evolutionary and phylogenetic relationships in Glyptothorax species through comparative mitochondrial genomics.Journal, genetic engineering & biotechnology · 2026Article
- ΦX174 bacteriophage viability predicted by protein biophysical modeling.bioRxiv : the preprint server for biology · 2025Article
- Large-scale experimental assessment of variant effects on the structure and function of the citrate transporter SLC13A5.Science advances · 2025Article
- Exploring the effects of missense mutations on protein thermodynamics through structure-based approaches: findings from the CAGI6 challenges.Human genetics · 2025Article
- Droplet microfluidic screening to engineer angiotensin-converting enzyme 2 (ACE2) catalytic activity.Journal of biological engineering · 2025Article
- The Genetic Consequences of Range Expansion and Its Influence on Diploidization in Polyploids.The American naturalist · 2025Article
- The genetic consequences of range expansion and its influence on diploidization in polyploids.bioRxiv : the preprint server for biology · 2024Article
- ProteinGym: Large-Scale Benchmarks for Protein Design and Fitness Prediction.bioRxiv : the preprint server for biology · 2023Article
- MBE: model-based enrichment estimation and prediction for differential sequencing data.Genome biology · 2023Article
- Genome-wide prediction of disease variant effects with a deep protein language model.Nature genetics · 2023Article
- A comprehensive map of human glucokinase variant activity.Genome biology · 2023Article
- Fitness and Functional Landscapes of the E. coli RNase III Gene rnc.Molecular biology and evolution · 2023Article
- The Mutational Landscape of Cancer's Vulnerability to Ionizing Radiation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Mechanisms of protein evolution.Protein science : a publication of the Protein Society · 2022Review
- Odd one out? Functional tuning of Zymomonas mobilis pyruvate kinase is narrower than its allosteric, human counterpart.Protein science : a publication of the Protein Society · 2022Article
- Sequence dependencies and biophysical features both govern cleavage of diverse cut-sites by HIV protease.Protein science : a publication of the Protein Society · 2022Article
- Article
- Computational approaches for predicting variant impact: An overview from resources, principles to applications.Frontiers in genetics · 2022Review
- Evolutionary coupling range varies widely among enzymes depending on selection pressure.Biophysical journal · 2021Article
- Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness.Virus evolution · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors.
Funding
Abstract
The last decade has seen a growing number of experiments aimed at systematically mapping the effects of mutations in different proteins, and of attempting to correlate their biophysical and biochemical effects with organismal fitness. While insightful, systematic laboratory measurements of fitness effects present challenges and difficulties. Here, we discuss the limitations associated with such measurements, and in particular the challenge of correlating the effects of mutations at the single protein level ("protein fitness") with their effects on organismal fitness. A variety of experimental setups are used, with some measuring the direct effects on protein function and others monitoring the growth rate of a model organism carrying the protein mutants. The manners by which fitness effects are calculated and presented also vary, and the conclusions, including the derived distributions of fitness effects of mutations, vary accordingly. The comparison of the effects of mutations in the laboratory to the natural protein diversity, namely to amino acid changes that have fixed in the course of millions of years of evolution, is also debatable. The results of laboratory experiments may, therefore, be less relevant to understanding long-term inter-species variations yet insightful with regard to short-term polymorphism, for example, in the study of the effects of human SNPs.
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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.