ArticleMolecular biology and evolution2020
Enhancers Facilitate the Birth of De Novo Genes and Gene Integration into Regulatory Networks.
Article in Molecular biology and evolution, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 60 citations in OpenAlex.
- Review
- Emergence Biases in Molecular Evolution.Genome biology and evolution · 2026Review
- Emergence and evolution of protein-coding de novo genes.Nature reviews. Genetics · 2026Review
- Epromoters bind key stress-related transcription factors to regulate clusters of stress response genes.The EMBO journal · 2026Article
- Multiple human enhancer RNAs contain long translated open reading frames.Genes & development · 2025Article
- The Genomic Kaleidoscope: On the Hidden Dimensions of Within-Species Genomic Diversity.Genome biology and evolution · 2025Review
- Improved sampling of genotypes and species reveals new insights on de novo gene history and regulatory origins.Genetics · 2025Article
- The highly rugged yet navigable regulatory landscape of the bacterial transcription factor TetR.Nature communications · 2024Article
- De Novo Genes.Annual review of genetics · 2024Review
- Massively integrated coexpression analysis reveals transcriptional regulation, evolution and cellular implications of the yeast noncanonical translatome.Genome biology · 2024Article
- DNA Transposons Favor De Novo Transcript Emergence Through Enrichment of Transcription Factor Binding Motifs.Genome biology and evolution · 2024Article
- A Synergistic, Cultivator Model of De Novo Gene Origination.Genome biology and evolution · 2024Article
- The origin and structural evolution of de novo genes in Drosophila.Nature communications · 2024Article
- From sequence to consequence: Deciphering the complex cisregulatory landscape.Journal of biosciences · 2024Article
- Evolutionarily conserved enhancer-associated features within theFrontiers in cell and developmental biology · 2024Article
- Gene birth in a model of non-genic adaptation.BMC biology · 2023Article
- Cell-specific and shared regulatory elements control a multigene locus active in mammary and salivary glands.Nature communications · 2023Article
- Evolution and implications of de novo genes in humans.Nature ecology & evolution · 2023Review
- Population genomics reveals mechanisms and dynamics of de novo expressed open reading frame emergence inGenome research · 2023Article
- Neutral Models of De Novo Gene Emergence Suggest that Gene Evolution has a Preferred Trajectory.Molecular biology and evolution · 2023Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulatory networks control the spatiotemporal gene expression patterns that give rise to and define the individual cell types of multicellular organisms. In eumetazoa, distal regulatory elements called enhancers play a key role in determining the structure of such networks, particularly the wiring diagram of "who regulates whom." Mutations that affect enhancer activity can therefore rewire regulatory networks, potentially causing adaptive changes in gene expression. Here, we use whole-tissue and single-cell transcriptomic and chromatin accessibility data from mouse to show that enhancers play an additional role in the evolution of regulatory networks: They facilitate network growth by creating transcriptionally active regions of open chromatin that are conducive to de novo gene evolution. Specifically, our comparative transcriptomic analysis with three other mammalian species shows that young, mouse-specific intergenic open reading frames are preferentially located near enhancers, whereas older open reading frames are not. Mouse-specific intergenic open reading frames that are proximal to enhancers are more highly and stably transcribed than those that are not proximal to enhancers or promoters, and they are transcribed in a limited diversity of cellular contexts. Furthermore, we report several instances of mouse-specific intergenic open reading frames proximal to promoters showing evidence of being repurposed enhancers. We also show that open reading frames gradually acquire interactions with enhancers over macroevolutionary timescales, helping integrate genes-those that have arisen de novo or by other means-into existing regulatory networks. Taken together, our results highlight a dual role of enhancers in expanding and rewiring gene regulatory networks.
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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.