ArticlePLoS genetics2020
Population genetic models of GERP scores suggest pervasive turnover of constrained sites across mammalian evolution.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
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- Long-term isolation and introgression shape the genomic distinctiveness of Rice's Whale.bioRxiv : the preprint server for biology · 2026Article
- Pervasive cryptic selection in the human noncoding genome.bioRxiv : the preprint server for biology · 2026Article
- Semantic embedding of variant effect annotations enables rapid and accurate pathogenicity prediction with VUS.Life.Scientific reports · 2026Article
- Single-base resolution atlas reveals moderate conservation and regulatory diversity of m6A modifications across mammals.Nucleic acids research · 2026Article
- The relationship between genomic variation and genetic load: insights from small island populations.Heredity · 2026Article
- SyMetrics: an integrated machine learning model for evaluating the pathogenicity of synonymous variants in the human genome.NAR genomics and bioinformatics · 2026Article
- Sharing approaches in predictive genomics across animals, plants and humans.Nature genetics · 2026Review
- The performance of genetic-constraint metrics varies significantly across the human noncoding genome.bioRxiv : the preprint server for biology · 2026Article
- Framework for assessing genetic variation in livestock using demographic, pedigree, and genomic measures.Frontiers in genetics · 2026Review
- PlantCAD2: A Long-Context DNA Language Model for Cross-Species Functional Annotation in Angiosperms.bioRxiv : the preprint server for biology · 2025Article
- ssG4-seq for global profiling of strand-specific G-quadruplex structures in mammalian genomes.Nature communications · 2025Article
- Genome-wide selection inference at short tandem repeats.PLoS genetics · 2025Article
- Unveiling the regulatory potential of the non-coding genome: Insights from the human genome project to precision medicine.Genes & diseases · 2025Review
- A fixed mutation in the respiratory complex I impairs mitochondrial bioenergetics in the endangered Apennine brown bear.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genome-wide association study reveals candidate loci on ECA1 and ECA9 for withers height in Friesian horses.Animal genetics · 2025Article
- Predicted deleterious mutations reveal the genetic architecture of male reproductive success in a lekking bird.Nature ecology & evolution · 2025Article
19 more citing papers are in PubMed but not listed here.
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3 authors.
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Abstract
Comparative genomic approaches have been used to identify sites where mutations are under purifying selection and of functional consequence by searching for sequences that are conserved across distantly related species. However, the performance of these approaches has not been rigorously evaluated under population genetic models. Further, short-lived functional elements may not leave a footprint of sequence conservation across many species. We use simulations to study how one measure of conservation, the Genomic Evolutionary Rate Profiling (GERP) score, relates to the strength of selection (Nes). We show that the GERP score is related to the strength of purifying selection. However, changes in selection coefficients or functional elements over time (i.e. functional turnover) can strongly affect the GERP distribution, leading to unexpected relationships between GERP and Nes. Further, we show that for functional elements that have a high turnover rate, adding more species to the analysis does not necessarily increase statistical power. Finally, we use the distribution of GERP scores across the human genome to compare models with and without turnover of sites where mutations are under purifying selection. We show that mutations in 4.51% of the noncoding human genome are under purifying selection and that most of this sequence has likely experienced changes in selection coefficients throughout mammalian evolution. Our work reveals limitations to using comparative genomic approaches to identify deleterious mutations. Commonly used GERP score thresholds miss over half of the noncoding sites in the human genome where mutations are under purifying selection.
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