ArticlePLoS genetics2008
Assessing the evolutionary impact of amino acid mutations in the human genome.
Article in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 412 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
412 citing papers in PubMed, 709 citations in OpenAlex.
- Whole-exome analysis in Tunisian Imazighen and Arabs shows the impact of demography in functional variation.Scientific reports · 2021Trial
- Recombination shapes the dynamics of selective constraint in global populations of human gut bacteria.PLoS biology · 2026Article
- Accelerated Evolution of Context-Dependent Gene Expression in Primate Immune Cells.bioRxiv : the preprint server for biology · 2026Article
- The distribution of fitness effects of nonsynonymous mutations varies phylogenetically across animals.PLoS biology · 2026Article
- Neural posterior estimation for population genetics.Genetics · 2026Article
- Inference of elevated mutation rates and variant effects using 700k exomes.bioRxiv : the preprint server for biology · 2026Article
- Causal inference clarifies the roles of background selection and mutation rate variation in shaping human genetic diversity.bioRxiv : the preprint server for biology · 2026Article
- Historically Small Population Size Limits Purging of Deleterious Mutations in a Conservation-Reliant Species, the Kirtland's Warbler.bioRxiv : the preprint server for biology · 2026Article
- Inferring Patterns of Purifying, Positive, and Balancing Selection in the Coppery Titi Monkey (Plecturocebus cupreus) Utilizing a Well-Fit Evolutionary Baseline Model.Genome biology and evolution · 2026Article
- Identifying Adaptive Footprints in the Presence of Demographic Uncertainty.Genome biology and evolution · 2026Article
- Neural posterior estimation for population genetics.bioRxiv : the preprint server for biology · 2026Article
- A new perspective on population genetics: Deciphering the relationship between genetic variants and disease prevalence in Psoriasis.PloS one · 2026Article
- The impact of non-neutral synonymous mutations when inferring selection on nonsynonymous mutations.Genetics · 2025Article
- Recent Insights Into the Evolutionary Genomics of the Critically Endangered Aye-Aye (Daubentonia madagascariensis).American journal of primatology · 2025Review
- Dynamics of dN/dS within recombining bacterial populations.bioRxiv : the preprint server for biology · 2025Article
- Drivers of achiasmatic meiosis: sexual antagonism versus heteromorphy-dependent aneuploidy across sex-chromosome divergence.G3 (Bethesda, Md.) · 2025Article
- Article
- A model for background selection in non-equilibrium populations.bioRxiv : the preprint server for biology · 2025Article
- Estimating the Distribution of Fitness Effects in Aye-Ayes (Daubentonia madagascariensis), Accounting for Population History as Well as Mutation and Recombination Rate Heterogeneity.American journal of primatology · 2025Article
- Study design and the sampling of deleterious rare variants in biobank-scale datasets.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
352 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
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Quantifying the distribution of fitness effects among newly arising mutations in the human genome is key to resolving important debates in medical and evolutionary genetics. Here, we present a method for inferring this distribution using Single Nucleotide Polymorphism (SNP) data from a population with non-stationary demographic history (such as that of modern humans). Application of our method to 47,576 coding SNPs found by direct resequencing of 11,404 protein coding-genes in 35 individuals (20 European Americans and 15 African Americans) allows us to assess the relative contribution of demographic and selective effects to patterning amino acid variation in the human genome. We find evidence of an ancient population expansion in the sample with African ancestry and a relatively recent bottleneck in the sample with European ancestry. After accounting for these demographic effects, we find strong evidence for great variability in the selective effects of new amino acid replacing mutations. In both populations, the patterns of variation are consistent with a leptokurtic distribution of selection coefficients (e.g., gamma or log-normal) peaked near neutrality. Specifically, we predict 27-29% of amino acid changing (nonsynonymous) mutations are neutral or nearly neutral (|s|<0.01%), 30-42% are moderately deleterious (0.01%<|s|<1%), and nearly all the remainder are highly deleterious or lethal (|s|>1%). Our results are consistent with 10-20% of amino acid differences between humans and chimpanzees having been fixed by positive selection with the remainder of differences being neutral or nearly neutral. Our analysis also predicts that many of the alleles identified via whole-genome association mapping may be selectively neutral or (formerly) positively selected, implying that deleterious genetic variation affecting disease phenotype may be missed by this widely used approach for mapping genes underlying complex traits.
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.