ArticleNature genetics2025
Conservation of regulatory elements with highly diverged sequences across large evolutionary distances.
Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Flexible use of conserved motifs constrains genome access in cell type evolution.Nature ecology & evolution · 2026Article
- A putativebioRxiv : the preprint server for biology · 2026Article
- Bridging precision agriculture and human medicine through comparative genetics.Nature reviews. Genetics · 2026Review
- Pig Matrix: a matched multiomics 3D regulatory genomics database for evolutionary and comparative analyses in pigs.Molecular biology and evolution · 2026Article
- ATACompass enables cross-species cell identity mapping for scATAC-seq without gene annotations.Cell reports methods · 2026Article
- Positive selection on brain cis-regulatory elements in the human lineage drives changes in gene expression and susceptibility to neuropsychiatric disorders.HGG advances · 2026Article
- Retinoic Acid Informs the Positional Identity of Frontonasal Neural Crest Cells Through Alx Family of Transcription Factors.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Article
- Evolutionary transfer learning enables organism-wide inference of mammalian enhancer landscapes.bioRxiv : the preprint server for biology · 2026Article
- Modular genetic architecture underlies human hand and foot evolution.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Decoding the enhancer-driven regulatory network for lactoferrin across mammalian species.Zoological research · 2026Article
- Cis-regulatory evolution shapes facial diversity in birds and mammals.Science advances · 2026Article
- Molecular systems, human noncoding sequence variants, and blood pressure.Physiological reviews · 2026Review
- Decoding thebioRxiv : the preprint server for biology · 2026Article
- Deep evolutionary conservation of a sex-determining locus without sequence homology.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Enhancing TFEA.ChIP with ENCODE regulatory maps for generalizable transcription factor enrichment.Briefings in bioinformatics · 2026Article
- Widespread turnover of a conserved cis-regulatory code across 589 grass species.Molecular biology and evolution · 2026Article
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- Conservation of cis-regulatory codes over half a billion years of evolution.Science advances · 2025Article
- A novel Hox gene promoter fuels the evolution of adaptive phenotypic plasticity in wing eyespots of satyrid butterflies.Nature ecology & evolution · 2025Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Developmental gene expression is a remarkably conserved process, yet most cis-regulatory elements (CREs) lack sequence conservation, especially at larger evolutionary distances. Some evidence suggests that CREs at the same genomic position remain functionally conserved independent of sequence conservation. However, the extent of such positional conservation remains unclear. Here, we profiled the regulatory genome in mouse and chicken embryonic hearts at equivalent developmental stages and found that most CREs lack sequence conservation. To identify positionally conserved CREs, we introduced the synteny-based algorithm interspecies point projection, which identifies up to fivefold more orthologs than alignment-based approaches. We termed positionally conserved orthologs 'indirectly conserved' and showed that they exhibited chromatin signatures and sequence composition similar to sequence-conserved CREs but greater shuffling of transcription factor binding sites between orthologs. Finally, we validated indirectly conserved chicken enhancers using in vivo reporter assays in mouse. By overcoming alignment-based limitations, we revealed widespread functional conservation of sequence-divergent CREs.
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