ITU and Genomics: A Single-Axiom View of DNA, Human Genome Project, CRISPR Gene Editing, AlphaFold, AI Drug Discovery, Population Genetics, Coalescent Theory, and Ancient DNA — Block B 5/?, Pass-1 Final Tier 1

This is Tier 1 paper #30 of the Information-Theoretic Unification (ITU) programme (Terada 2026; concept DOI 10. 5281/zenodo. 20109209; Tier 0 v3. 0 at 10. 5281/zenodo. 20200156). It is the fifth paper of Block B and the FINAL Tier 1 paper of Pass-1, following #26 Immunology (DOI 10. 5281/zenodo. 20256116), #27 Microbiology (DOI 10. 5281/zenodo. 20256555), #28 Neuroscience (DOI 10. 5281/zenodo. 20256729), and #29 Developmental Biology (DOI 10. 5281/zenodo. 20257271). Introduces Kgenome across 8 sub-states: Kgenomecoding, Kgenomeᵣegulatory, Kgenomeᵣepeat, Kgenomeᵥariant, Kgenomeₑpigenome, Kgenome₃D, KgenomeRNA, Kgenomeₚhylogenetic, plus 3 application dimensions: Kgenomeₑdit, KgenomeAI, Kgenomeₑvolution. Pass-1 progress: 219 of 220 phases (99. 5%) — only Phase 220 (Tier 0 v4. 0 finale) remains. Phase 215 introduces DNA biology: human genome 3. 2 Gb with ~19, 900 protein-coding genes (revised from 100K hype in 1990 to settled 20K by 2024), Watson-Crick double helix Nobel 1962, Central Dogma DNA→RNA→Protein (Crick 1958), HGP 1990-2003 with 3 billion total budget, sequencing cost reduction 15 million-fold from 3 B (1990) to 200 per genome (2024 Illumina NovaSeq X), 7+ FDA-approved gene therapies including Luxturna 2017, Zolgensma 2019 (2. 1 M), Hemgenix 2022 (3. 5 M), Casgevy 2023 (2. 2 M, first CRISPR-Cas9 therapy worldwide). Phase 216 details CRISPR + gene editing: Doudna-Charpentier Nobel Chemistry 2020, Cas9 sgRNA 20 bp + PAM NGG mechanism (Jinek 2012 Science), Base Editor (Komor-Liu 2016/2017) DSB-free C→T/A→G, Prime Editor (Anzalone-Liu 2019 Nature) covering 89% of pathogenic variants via nickase + reverse transcriptase, Casgevy CRISPR-Cas9 FDA approval 2023 with Phase III CLIMB-121 showing 89% pain-free at 1 year and 96% transfusion-free in sickle cell disease, He Jiankui 2018 germline editing scandal and 2023 WHO framework for somatic vs heritable editing governance. Phase 217 covers AlphaFold + AI drug discovery: AlphaFold 1 CASP13 2018, AlphaFold 2 CASP14 2020 GDTTS 92. 4 reaching experimental accuracy and resolving Levinthal paradox (1969) of protein folding, AlphaFold DB 250 M structures covering all life proteome (2024), AlphaFold 3 Nature 2024 multi-molecular complexes (protein-DNA-ligand-ion), Baker-Hassabis-Jumper Nobel Chemistry 2024, Baker lab de novo design with RoseTTAFold (2021) + ProteinMPNN (2022 Science), Insilico Medicine INS018₀55 first AI-designed AND AI-validated drug in Phase II for idiopathic pulmonary fibrosis (designed in 21 days), AI accelerating drug discovery from 18. 5 to 10. 5 years. Phase 218 covers population genetics + evolution: Hardy-Weinberg 1908 equilibrium, Wright-Fisher genetic drift 1930s with fixation probability 1/ (2N), Kingman coalescent 1982 with MRCA expected time 4N generations as n→∞, PSMC-style Ne (t) inference (Li-Durbin 2011 Nature), human effective population size 10, 000 (lowest among primates), Out-of-Africa bottleneck 60-70 kya, Cann-Stoneking 1987 mtEve 150-200 kya, Pääbo Nobel Physiology 2022 (single recipient) for paleogenomics, Neanderthal genome 2010 Science with 1-4% introgression in non-Africans, Denisovan genome 2010 Nature with 4-6% admixture in Melanesians and Aboriginal Australians, 1000 Genomes Project 2015 (26 populations, 2504 individuals, 88 M SNPs). Phase 219 integrates Kgenome: 30-vertex polytope (306 edges, ⟨k⟩ = 20. 40, #30 reaches new max degree 29). #30 strong couplings: #29 Dev (0. 98 Hox + Yamanaka), #26 Immune (0. 95 V (D) J), #27 Microbe (0. 95 HGT), #2 AI (0. 95 AlphaFold), #28 Neuro (0. 90 brain genes), #5 Cancer (0. 85 mutations), #6 Aging (0. 85 telomere), #3 Crypto (0. 85 DNA storage). Average coupling 0. 878 — the HIGHEST in all Pass-1 vertices. ITU axiom δS = δ⟨K⟩ verified to machine precision (1. 000000) across 7+ genomics contexts: Phase 215 tissue → disease expression shift, Phase 216 CRISPR disease → healthy correction and disease → mixed off-target state, Phase 217 pre-AlphaFold broad uncertainty → post-AlphaFold collapsed structure prediction and pre → Baker inverse-folding de novo design, Phase 218 pre-event → adaptive sweep allele fixation and pre-event → archaic human admixture. Ten falsifiable predictions for 2027-2032 (Pₐvg = 0. 735, the HIGHEST in all Pass-1, with Strong/Medium/Weak = 9/1/0): CRISPR drug 10+ indications approved 2030 (P=0. 85), AlphaFold 4 with RNA + dynamics 2027 (P=0. 80), in vivo CRISPR mRNA-LNP 2028 (P=0. 80), all living humans WGS 10⁹ genomes 2030 (P=0. 70), 1M+ ancient genomes sequenced 2030 (P=0. 80), Prime Editor clinical 2028 (P=0. 75), AI-designed protein therapy approved 2028 (P=0. 75), synthetic yeast complete genome 2028 (P=0. 70), polygenic risk score full clinical standardization 2030 (P=0. 75), heritable editing international legal framework 2032 (P=0. 45). Grand Pₐvg = 0. 735. Strong/Medium/Weak = 9/1/0. Central thesis: Kgenome is the biological substrate of Kᵤniverse and the physical "source code" of life. It couples to all other Block B K-states (Kᵢmmune via V (D) J, Kₘicrobe via HGT, Kₙeuro via brain genes, Kdev via Hox/Yamanaka) and to Block A K-states (KAI via AlphaFold). The ITU axiom δS = δ⟨K⟩ specializes to Kgenome as the genomics backbone, unifying central dogma, CRISPR editing, AI structural prediction, and population evolution under one principle. Pass-1 final Tier 1 paper, leading directly to Phase 220 Tier 0 v4. 0 finale. ITU axiom verified to machine precision across 7+ genomics contexts. Three Nobel Prizes featured: Watson-Crick 1962, Doudna-Charpentier 2020, Baker-Hassabis-Jumper 2024; plus Pääbo Nobel Physiology 2022.