ArticleNature genetics2013
Genome-wide inference of natural selection on human transcription factor binding sites.
Article in Nature genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 151 citations in OpenAlex.
- The distribution of fitness effects of nonsynonymous mutations varies phylogenetically across animals.PLoS biology · 2026Article
- Identifying causal genetic variants for high-altitude adaptation through blood eQTL analysis in plateau populations.Communications biology · 2026Article
- Natural Selection in Transcription Factor-DNA Interaction Motifs: A Comparative and Population Genomics Perspective.Genome biology and evolution · 2025Article
- Article
- Epistatic contributions to human traits via transcription factor mechanisms.medRxiv : the preprint server for health sciences · 2025Article
- The landscape of fitness effects of putatively functional noncoding mutations in humans.bioRxiv : the preprint server for biology · 2025Article
- Cross-ancestry analysis of brain QTLs enhances interpretation of schizophrenia genome-wide association studies.American journal of human genetics · 2024Article
- Structural underpinnings of mutation rate variations in the human genome.Nucleic acids research · 2023Article
- Single-cell dissection of aggression in honeybee colonies.Nature ecology & evolution · 2023Article
- The genetics of autism spectrum disorder in an East African familial cohort.Cell genomics · 2023Article
- Transcription factor binding sites are frequently under accelerated evolution in primates.Nature communications · 2023Article
- Exploration of Tools for the Interpretation of Human Non-Coding Variants.International journal of molecular sciences · 2022Review
- Prediction of evolutionary constraint by genomic annotations improves functional prioritization of genomic variants in maize.Genome biology · 2022Article
- Extreme purifying selection against point mutations in the human genome.Nature communications · 2022Article
- Systems biology analysis of human genomes points to key pathways conferring spina bifida risk.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Genetic Variants in Transcription Factor Binding Sites in Humans: Triggered by Natural Selection and Triggers of Diseases.International journal of molecular sciences · 2021Review
- Impact of Genetic Variation in Gene Regulatory Sequences: A Population Genomics Perspective.Frontiers in genetics · 2021Review
- Learning the Regulatory Code of Gene Expression.Frontiers in molecular biosciences · 2021Review
- Deep learning suggests that gene expression is encoded in all parts of a co-evolving interacting gene regulatory structure.Nature communications · 2020Article
- Robust inference of positive selection on regulatory sequences in the human brain.Science advances · 2020Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
For decades, it has been hypothesized that gene regulation has had a central role in human evolution, yet much remains unknown about the genome-wide impact of regulatory mutations. Here we use whole-genome sequences and genome-wide chromatin immunoprecipitation and sequencing data to demonstrate that natural selection has profoundly influenced human transcription factor binding sites since the divergence of humans from chimpanzees 4-6 million years ago. Our analysis uses a new probabilistic method, called INSIGHT, for measuring the influence of selection on collections of short, interspersed noncoding elements. We find that, on average, transcription factor binding sites have experienced somewhat weaker selection than protein-coding genes. However, the binding sites of several transcription factors show clear evidence of adaptation. Several measures of selection are strongly correlated with predicted binding affinity. Overall, regulatory elements seem to contribute substantially to both adaptive substitutions and deleterious polymorphisms with key implications for human evolution and disease.
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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.