ArticleNature ecology & evolution2023
De novo genes with an lncRNA origin encode unique human brain developmental functionality.
Article in Nature ecology & evolution, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 68 citations in OpenAlex.
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- Phylostratigraphic Analysis Reveals the Evolutionary Origins and Potential Role of New Genes in the Adaptive Evolution ofInternational journal of molecular sciences · 2026Article
- Opportunities and challenges in studying non-coding RNAs using neural organoid models.Frontiers in molecular neuroscience · 2026Review
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- De Novo Genes: Current Status and Future Goals.Genome biology and evolution · 2025Article
- Orphan and de novo Genes in Fungi and Animals: Identification, Origins and Functions.Genome biology and evolution · 2025Review
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- Mitochondrial Microproteins: Emerging Regulators in Neurodevelopment and Neurodegeneration.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Importance of De Novo Gene Evolution to Emerging Viral Threats: The ORF10 Strain-Restricted Orphan Gene of SARS-CoV-2 Promotes Pathogenesis.Molecular biology and evolution · 2025Article
- Oncogenic roles of young human de novo genes and their potential as neoantigens in cancer immunotherapy.Cell genomics · 2025Article
- Improved sampling of genotypes and species reveals new insights on de novo gene history and regulatory origins.Genetics · 2025Article
- Eukaryotic Microproteins.Annual review of biochemistry · 2025Review
- Genomic Analysis Reveals the Role of New Genes in Venom Regulatory Network of Parasitoid Wasps.Insects · 2025Article
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20 authors at 6 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Human de novo genes can originate from neutral long non-coding RNA (lncRNA) loci and are evolutionarily significant in general, yet how and why this all-or-nothing transition to functionality happens remains unclear. Here, in 74 human/hominoid-specific de novo genes, we identified distinctive U1 elements and RNA splice-related sequences accounting for RNA nuclear export, differentiating mRNAs from lncRNAs, and driving the origin of de novo genes from lncRNA loci. The polymorphic sites facilitating the lncRNA-mRNA conversion through regulating nuclear export are selectively constrained, maintaining a boundary that differentiates mRNAs from lncRNAs. The functional new genes actively passing through it thus showed a mode of pre-adaptive origin, in that they acquire functions along with the achievement of their coding potential. As a proof of concept, we verified the regulations of splicing and U1 recognition on the nuclear export efficiency of one of these genes, the ENSG00000205704, in human neural progenitor cells. Notably, knock-out or over-expression of this gene in human embryonic stem cells accelerates or delays the neuronal maturation of cortical organoids, respectively. The transgenic mice with ectopically expressed ENSG00000205704 showed enlarged brains with cortical expansion. We thus demonstrate the key roles of nuclear export in de novo gene origin. These newly originated genes should reflect the novel uniqueness of human brain development.
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