Human Chromosome 2 Fusion in Hominin Evolution: Cytogenetic Evidence, Drift-Aware Establishment Under Underdominance, and T2T-Era Paleogenomic Audits

Human chromosome 2 (HSA2) originated from a telomere-to-telomere fusion event in thehuman lineage, supported by convergent cytogenetic and comparative-genomic signatures. The primaryunresolved questions are quantitative and empirical: how an (at least partially) underdominantrearrangement could establish under drift and realistic population structure, and whether fusion-proximalsequence behaved as a barrier to gene flow during later admixture with archaic hominins. Here, weintegrate (i) drift-aware Wright–Fisher simulations and a simple subdivided metapopulation model toquantify establishment probabilities under heterozygote fertility costs, including sensitivity to weaktransmission-ratio distortion (TRD; k>0.5); (ii) a tract-based assay of Neanderthal introgression at 2q13using a public IBDmix Vindija callset (hg19) benchmarked against a length-matched chromosome 2 null;and (iii) external evidence from recent T2T-CHM13 audits showing that reference completeness rescuessubstantial archaic sequence previously undetected in repeat-rich regions, constraining interpretations ofapparent 'introgression deserts' near pericentromeric sequence. Taken together, these results supportconservative, testable claims: establishment of an underdominant fusion is plausible under drift instructured populations and can be amplified by weak TRD, whereas introgression depletion at 2q13 inhg19-era callsets must be interpreted cautiously given callability vulnerabilities highlighted by T2T-basedremapping.