197: Somatic Mutation and Selection at Population Scale

Somatic Mutation and Selection at Population Scale Music:Enjoy the music based on this article at the end of the episode. License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/somatic-mutation-and-selection-at-population-scale ️ Episode:197: Somatic Mutation and Selection at Population Scale ️ Season:1 Article title:Somatic mutation and selection at population scale Journal:Nature DOI:10.1038/s41586-025-09584-w QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-11-13. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited spoken content for alignment with the article's main findings: NanoSeq methodology and ultra-low error sequencing; age-related somatic mutation accumulation in oral epithelium; driver landscape (NOTCH1, TP53, FAT1); in vivo saturation mutagenesis and hotspots (TP53 DNA-binding domain; RAC1); clonal growth dynam- transcript topics: NanoSeq methodology and ultra-low error sequencing; Age-related somatic mutation accumulation in oral epithelium; Driver landscape and positive selection in oral epithelium; In vivo saturation mutagenesis and hotspot mapping (TP53 DNA-binding domain; RAC1 GTP-binding pocket); Clonal growth dynamics and tissue architectural plateau; Alcohol-related mutational signatures and ALDH2 genetics QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 8- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- NanoSeq achieves error rate below five errors per billion base pairs- Age-related somatic mutation accumulation in oral epithelium ~18 SNVs per cell per year- Driver landscape includes 46 genes under positive selection and >62,000 driver mutations in oral epithelium- NOTCH1, TP53 and FAT1 are among strongest driver genes in oral epithelium- Approximately 10–20% of cheek cells carry a driver mutation in older individuals- In vivo saturation mutagenesis identifies hotspots in TP53 DNA-binding domain and RAC1 GTP-binding pocket QC result: Pass.