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Research: Endonucleolytic cleavage is the primary mechanism of decay elicited by C. elegans nonsense-mediated mRNA decay
- Marcus J. Viscardi,
- Enisha Sehgal,
- and Joshua A. Arribere
Genome Res. June 2025 35: 1337-1348; Published in Advance May 9, 2025, doi:10.1101/gr.280046.124
...easily mutated than the other SMG genes, and NMD function can be restored to SMG7-mutant cells via high expression of SMG5 (Boehm et al. 2021). In Drosophila melanogaster, SMG7 is absent (Gatfield et al. 2003).Taken together, our results support the model that SMG-5, SMG-6, and SMG-7 work together...
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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
...was below the threshold (see Methods).FIE genes showed signals of positive selection, assessed using dN/dS (Fig. 2A; Supplemental Note 4), indicating significant enrichment in missense, nonsense, splice, and truncating mutations compared with synonymous variants. Pancancer FIEs showed positive cancer effect...
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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
...of mutation rates in germline and soma. Genetics 207: 255–267. doi:10.1534/genetics.117.1114 ↵Choux C, Binquet C, Carmignac V, Bruno C, Chapusot C, Barberet J, Lamotte M, Sagot P, Bourc'his D, Fauque P. 2018. The epigenetic control of transposable elements and imprinted genes in newborns is affected...
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Method: Robust and efficient annotation of cell states through gene signature scoring
- Laure Ciernik,
- Agnieszka Kraft,
- Florian Barkmann,
- Josephine Yates,
- and Valentina Boeva
Genome Res. March 2026 36: 630-644; Published in Advance February 18, 2026, doi:10.1101/gr.280926.125
...of the Austrian Academy of Sciences, 1090 Vienna, Austria; 11Eric and Wendy Schmidt Center, The Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA Corresponding author: valentina.boeva@inf.ethz.chAbstractGene signature scoring is integral to single-cell RNA sequencing (scRNA-seq) data analysis...
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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
...is noncoding as a result of gene inactivation after the ORFan emerged. To exclude this possibility, not only must the noncoding sequence display homology with the ORFan sequence but its “disabling” mutation (i.e., at least one start-codon disrupting mutation, stop-codon or frameshift mutation) must occur...
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Method: A scalable computational framework for predicting gene expression from candidate cis-regulatory elements
- Qinhu Zhang,
- Siguo Wang,
- Zhipeng Li,
- Wenzheng Bao,
- Wenjian Liu,
- and De-Shuang Huang
Genome Res. February 2026 36: 361-374; Published in Advance January 16, 2026, doi:10.1101/gr.281219.125
...a crucial role in differentiation and development (Furlong and Levine 2018). Mutations in CREs contribute to various diseases by disrupting the regular expression of their target genes (Nasser et al. 2021). Decoding how CREs regulate gene expression may reveal the mechanisms of gene regulation and provide...
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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
...introduce new elements, such as exogenous proteins, activating mutations, plasmids, artificial chromosomes, or knock-in modifications. Conversely, loss-of-function approaches remove specific factors using mutations, siRNA silencing, or gene-editing techniques. These modifications can be applied to either...
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Research: Analysis of canine gene constraint identifies new variants for orofacial clefts and stature
- Reuben M. Buckley,
- Nüket Bilgen,
- Alexander C. Harris,
- Peter Savolainen,
- Cafer Tepeli,
- Metin Erdoğan,
- Aitor Serres Armero,
- Dayna L. Dreger,
- Frank G. van Steenbeek,
- Marjo K. Hytönen,
- Heidi G. Parker,
- Jessica Hale,
- Hannes Lohi,
- Bengi Çınar Kul,
- Adam R. Boyko,
- and Elaine A. Ostrander
Genome Res. May 2025 35: 1080-1093; Published in Advance March 24, 2025, doi:10.1101/gr.280092.124
...of variants related to craniofacial morphology and stature. Breed-enriched variants were prioritized according to gene constraint, which was calculated using a mutation model derived from trinucleotide substitution probabilities. Among the newly found variants is a splice-acceptor variant in PDGFRA associated...
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Research: Hydra has mammal-like mutation rates facilitating fast adaptation despite its nonaging phenotype
- Arne Sahm,
- Konstantin Riege,
- Marco Groth,
- Martin Bens,
- Johann Kraus,
- Martin Fischer,
- Hans Kestler,
- Christoph Englert,
- Ralf Schaible,
- Matthias Platzer,
- and Steve Hoffmann
Genome Res. December 2024 34: 2217-2228; Published in Advance December 4, 2024, doi:10.1101/gr.279025.124
...” variations are strictly biallelic and are present in all cells of the genet—unless a locus is affected by a second mutation and the resulting allele is transmitted to a subset of cells.In Hydra oligactis, lowering the water temperature can induce aging. Gene expression comparisons between aging and nonaging...
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Research: A gene regulatory element modulates myosin expression and controls cardiomyocyte response to stress
- Taylor Anglen,
- Irene M. Kaplow,
- Baekgyu Choi,
- Enya Dewars,
- Robin M. Perelli,
- Kevin T. Hagy,
- Duc Tran,
- Megan E. Ramaker,
- Svati H. Shah,
- Inkyung Jung,
- Andrew P. Landstrom,
- Ravi Karra,
- Yarui Diao,
- and Charles A. Gersbach
Genome Res. November 2025 35: 2418-2432; Published in Advance October 22, 2025, doi:10.1101/gr.280825.125
...defects during heart development (Ching et al. 2005). Despite years of research investigating the consequences of MYH6 silencing and loss-of-function mutations, the regulation of MYH6 remains incompletely understood.To better understand the function of noncoding gene regulation in CMs, we performed assay...
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