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Review: De novo gene birth and the conundrum of ORFan genes in bacteria
- Md. Hassan uz-Zaman and
- Howard Ochman
Genome Res. August 2025 35: 1679-1688; Published in Advance July 10, 2025, doi:10.1101/gr.280157.124
...emerged transcription of a pre-existing ORF. (B) De novo gene emergence from a frameshifted gene sequence. (Created with BioRender; https://www.biorender.com/.)Merging comparative genomic and transcriptomic data allow detection of both the lineage-specific transcripts and the mutations responsible...
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Research: Intergenic ORFs as elementary structural modules of de novo gene birth and protein evolution
- Chris Papadopoulos,
- Isabelle Callebaut,
- Jean-Christophe Gelly,
- Isabelle Hatin,
- Olivier Namy,
- Maxime Renard,
- Olivier Lespinet,
- and Anne Lopes
Genome Res. December 2021 31: 2303-2315; Published in Advance November 22, 2021, doi:10.1101/gr.275638.121
...predicted as foldable. Then, we investigated the early stages of de novo gene birth by reconstructing the ancestral sequences of 70 yeast de novo genes and characterized the sequence and structural properties of intergenic ORFs with a strong translation signal. This enabled us to highlight sequence...
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Method: Gene duplication is associated with gene diversification and potential neofunctionalization in lung cancer evolution
- Paul Ashford,
- Alexander M. Frankell,
- Zofia Piszka,
- Camilla S.M. Pang,
- Mahnaz Abbasian,
- Maise Al Bakir,
- Mariam Jamal-Hanjani,
- Nicholas McGranahan,
- Charles Swanton,
- and Christine A. Orengo
Genome Res. March 2026 36: 561-577; Published in Advance February 19, 2026, doi:10.1101/gr.278663.123
...duplication events as a way of enhancing tumor adaptability. In addition, it is possible that some FIEs (including those in known cancer genes) result in neofunctional changes. Here, neofunctionalization refers to the emergence of a tumor-beneficial protein function that is distinct from the wild...
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Research: Population genomics reveals mechanisms and dynamics of de novo expressed open reading frame emergence in Drosophila melanogaster
- Anna Grandchamp,
- Lucas Kühl,
- Marie Lebherz,
- Kathrin Brüggemann,
- John Parsch,
- and Erich Bornberg-Bauer
Genome Res. June 2023 33: 872-890; Published in Advance July 13, 2023, doi:10.1101/gr.277482.122
...of de novo genes that emerged within a single species. We sequenced and assembled s with long-read technology and the corresponding transcriptomes from inbred lines of Drosophila melanogaster, derived from seven geographically diverse populations. We found line-specific neORFs in abundance but few neORFs...
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Method: Exon Nomenclature And Classification of Transcripts (ENACT) provides a systematic framework to annotate exon attributes
- Paras Verma,
- Deeksha Thakur,
- Deepanshi Awasthi,
- and Shashi Bhushan Pandit
Genome Res. June 2025 35: 1440-1455; Published in Advance May 7, 2025, doi:10.1101/gr.279878.124
...@iisermohali.ac.inAbstractIsoform diversity is known to enhance a gene's functional repertoire by producing protein variants with distinct functional implications. Despite numerous studies on transcriptome diversifying processes (alternative splicing/transcription), understanding their extent and correlated impact on proteome diversity...
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Research: Chimeric mitochondrial RNA transcripts predict mitochondrial genome deletion mutations in mitochondrial genetic diseases and aging
- Amy R. Vandiver,
- Allen Herbst,
- Paul Stothard,
- and Jonathan Wanagat
Genome Res. January 2025 35: 55-65; Published in Advance November 27, 2024, doi:10.1101/gr.279072.124
...mutants are functionally dominant over wild-type mitochondrial s in skeletal muscle fiber segments in mitochondrial disease. Cell 62: 43–49. doi:10.1016/0092-8674(90)90238-A ↵Shtivelman E, Lifshitz B, Gale RP, Canaani E. 1985. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature...
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Research: Modest increase in the de novo single-nucleotide mutation rate in house mice born by assisted reproduction
- Laura Blanco-Berdugo,
- Alexis Garretson,
- and Beth L. Dumont
Genome Res. January 2026 36: 50-60; Published in Advance November 13, 2025, doi:10.1101/gr.281180.125
...associated with H3K27ac, H3K36me3, H3K4me1, H3K4me3, H3K9ac, or H3K9me3 histone modifications in either mESCs or mouse embryos (Fisher's exact tests, P > 0.25) (Supplemental Figs. 7, 8).In somatic cells, transcription-coupled repair reduces dnSNV rates in highly expressed genes compared with more lowly...
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Review: A systematic guide for identifying transcription factors that directly regulate the expression of a gene of interest
- Andrew D. Bates,
- Dawid Grzela,
- Maciej Studzian,
- Louise Brennan,
- Moli Williams,
- Conor Fawcett,
- Beth Hammond,
- Manreen Grewal,
- Marcin Ratajewski,
- Lukasz Pulaski,
- and Urszula L. McClurg
Genome Res. March 2026 36: 433-459; Published in Advance February 17, 2026, doi:10.1101/gr.281154.125
...cellular conditions such as hypoxia, starvation, DNA damage, etc., to determine the cellular context required for GOI expression.Originally the nuclear run-on technique was developed to detect the emergent transcripts that are in the process of being produced from the GOI. In this approach, intact nuclei...
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Resource: Full-length RNA transcript sequencing traces brain isoform diversity in house mouse natural populations
- Wenyu Zhang,
- Anja Guenther,
- Yuanxiao Gao,
- Kristian Ullrich,
- Bruno Huettel,
- Aftab Ahmad,
- Lei Duan,
- Kaizong Wei,
- and Diethard Tautz
Genome Res. November 2024 34: 2118-2132; Published in Advance September 17, 2024, doi:10.1101/gr.279166.124
...: wyzhang@nwpu.edu.cn, tautz@evolbio.mpg.deAbstractThe ability to generate multiple RNA transcript isoforms from the same gene is a general phenomenon in eukaryotes. However, the complexity and diversity of alternative isoforms in natural populations remain largely unexplored. Using a newly developed full...
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Resource: Chromosome-level subgenome-aware de novo assembly provides insight into Saccharomyces bayanus genome divergence after hybridization
- Cory Gardner,
- Junhao Chen,
- Christina Hadfield,
- Zhaolian Lu,
- David Debruin,
- Yu Zhan,
- Maureen J. Donlin,
- Tae-Hyuk Ahn,
- and Zhenguo Lin
Genome Res. November 2024 34: 2133-2146; Published in Advance September 17, 2024, doi:10.1101/gr.279364.124
...diversification, adaptation, and speciation. To better understand the changes that occurred in the different subs of a hybrid species and how they facilitate adaptation, we have completed chromosome-level de novo assemblies of all chromosomes for a recently formed hybrid yeast, Saccharomyces bayanus strain CBS380...

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