ArticleNature communications2022
Extreme purifying selection against point mutations in the human genome.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- The distribution of fitness effects of new mutations in regulatory regions of thebioRxiv : the preprint server for biology · 2026Article
- The performance of genetic-constraint metrics varies significantly across the human noncoding genome.bioRxiv : the preprint server for biology · 2026Article
- Modest increase in the de novo single-nucleotide mutation rate in house mice born by assisted reproduction.Genome research · 2026Article
- Correlation analysis ofVeterinary research forum : an international quarterly journal · 2026Article
- Nucleotide Substitution Biases in Related Cancer Driver Genes.International journal of molecular sciences · 2025Article
- Transcription start sites experience a high influx of heritable variants fueled by early development.Nature communications · 2025Article
- A combined genomic arrhythmia propensity score delineates cumulative risk.Cell reports. Medicine · 2025Article
- Article
- varCADD: large sets of standing genetic variation enable genome-wide pathogenicity prediction.Genome medicine · 2025Article
- Single-cell transcriptomics of ventral forebrain progenitors identifies Evf2 enhancer lncRNA-enhancer gene guidance through direct RNA binding and RNP recruitment domains.Nature communications · 2025Article
- Increased rate ofbioRxiv : the preprint server for biology · 2025Article
- The landscape of fitness effects of putatively functional noncoding mutations in humans.bioRxiv : the preprint server for biology · 2025Article
- Interpreting mammalian synonymous site conservation in light of the unwanted transcript hypothesis.Nature communications · 2025Article
- Constraining models of dominance for nonsynonymous mutations in the human genome.PLoS genetics · 2024Article
- Computational identification of ultra-conserved elements in the human genome: a hypothesis on homologous DNA pairing.NAR genomics and bioinformatics · 2024Article
- Genetic diversity of 1,845 rhesus macaques improves genetic variation interpretation and identifies disease models.Nature communications · 2024Article
- Biases in ARG-Based Inference of Historical Population Size in Populations Experiencing Selection.Molecular biology and evolution · 2024Article
- Genomic analysis and phylogenetic characterization of Himalayan snow trout, Schizothorax esocinus based on mitochondrial protein-coding genes.Molecular biology reports · 2024Article
- A quantitative genetic model of background selection in humans.PLoS genetics · 2024Article
- Multi-omics analysis in human retina uncovers ultraconserved cis-regulatory elements at rare eye disease loci.Nature communications · 2024Article
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5 authors.
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Abstract
Large-scale genome sequencing has enabled the measurement of strong purifying selection in protein-coding genes. Here we describe a new method, called ExtRaINSIGHT, for measuring such selection in noncoding as well as coding regions of the human genome. ExtRaINSIGHT estimates the prevalence of "ultraselection" by the fractional depletion of rare single-nucleotide variants, after controlling for variation in mutation rates. Applying ExtRaINSIGHT to 71,702 whole genome sequences from gnomAD v3, we find abundant ultraselection in evolutionarily ancient miRNAs and neuronal protein-coding genes, as well as at splice sites. By contrast, we find much less ultraselection in other noncoding RNAs and transcription factor binding sites, and only modest levels in ultraconserved elements. We estimate that ~0.4-0.7% of the human genome is ultraselected, implying ~ 0.26-0.51 strongly deleterious mutations per generation. Overall, our study sheds new light on the genome-wide distribution of fitness effects by combining deep sequencing data and classical theory from population genetics.
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