ArticleNature structural & molecular biology2024
Regulatory activity is the default DNA state in eukaryotes.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 19 citations in OpenAlex.
- Genomic indicators of gene function: a systematic assessment of the human genome.G3 (Bethesda, Md.) · 2026Article
- Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026Review
- Emergence Biases in Molecular Evolution.Genome biology and evolution · 2026Review
- Toward generalizable and interpretable AI in regulatory genomics.Nature genetics · 2026Review
- ExoShorkie: predicting RNA-seq coverage of exogenous genomes in yeast by transfer learning.Bioinformatics (Oxford, England) · 2026Article
- Emergence and evolution of protein-coding de novo genes.Nature reviews. Genetics · 2026Review
- Pervasive Transcription in the Human Genome Exceeds Background Noise.Genome biology and evolution · 2026Article
- Why do we have so many different transcripts?PLoS biology · 2026Article
- Review
- The role of transposon activity in shapingGenome research · 2025Article
- Novelty versus innovation of gene regulatory elements in human evolution and disease.Current opinion in genetics & development · 2025Review
- Engineering structural variants to interrogate genome function.Nature genetics · 2024Review
- Interpreting cis-regulatory interactions from large-scale deep neural networks.Nature genetics · 2024Article
- Nonlethal deleterious mutation-induced stress accelerates bacterial aging.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- InterpretingbioRxiv : the preprint server for biology · 2024Article
- Identifying candidate de novo genes expressed in the somatic female reproductive tract of Drosophila melanogaster.G3 (Bethesda, Md.) · 2023Article
- Identifying candidatebioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genomes encode for genes and non-coding DNA, both capable of transcriptional activity. However, unlike canonical genes, many transcripts from non-coding DNA have limited evidence of conservation or function. Here, to determine how much biological noise is expected from non-genic sequences, we quantify the regulatory activity of evolutionarily naive DNA using RNA-seq in yeast and computational predictions in humans. In yeast, more than 99% of naive DNA bases were transcribed. Unlike the evolved transcriptome, naive transcripts frequently overlapped with opposite sense transcripts, suggesting selection favored coherent gene structures in the yeast genome. In humans, regulation-associated chromatin activity is predicted to be common in naive dinucleotide-content-matched randomized DNA. Here, naive and evolved DNA have similar co-occurrence and cell-type specificity of chromatin marks, challenging these as indicators of selection. However, in both yeast and humans, extreme high activities were rare in naive DNA, suggesting they result from selection. Overall, basal regulatory activity seems to be the default, which selection can hone to evolve a function or, if detrimental, repress.
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