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 K_genome across 8 sub-states: K_genome_coding, K_genome_regulatory, K_genome_repeat, K_genome_variant, K_genome_epigenome, K_genome_3D, K_genome_RNA, K_genome_phylogenetic, plus 3 application dimensions: K_genome_edit, K_genome_AI, K_genome_evolution. 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 GDT_TS 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 INS018_055 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 K_genome: 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 (P_avg = 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 P_avg = 0.735. Strong/Medium/Weak = 9/1/0. Central thesis: K_genome is the biological substrate of K_universe and the physical "source code" of life. It couples to all other Block B K-states (K_immune via V(D)J, K_microbe via HGT, K_neuro via brain genes, K_dev via Hox/Yamanaka) and to Block A K-states (K_AI via AlphaFold). The ITU axiom δS = δ⟨K⟩ specializes to K_genome 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.