chr2·hg38·242.2 Mb

Chromosome 2

The chromosome that proves we are apes: formed by the head-to-head fusion of two ancestral primate chromosomes, chromosome 2 carries within it the vestigial telomeres and a dead centromere — molecular fossils of the event that reduced the human karyotype from 48 to 46.

Physical Properties

Length242.2 Mb

Centromeremetacentric

p-arm92.2 Mb

q-arm148.1 Mb

GC content40.2%

Genomic Features

Protein-coding genes1,309

Gene density5.4 / Mb

CpG islands20,782

EPIC v2 probes73,979

Notable

Largest geneCNTNAP5 (1.3 Mb)

Disease associations

Lynch syndrome

Waardenburg syndrome

Alström syndrome

· Formed by fusion of two ancestral primate chromosomes

· Contains the HOXD cluster controlling limb development

· Second largest chromosome at 242 Mb

Genomic Architecture

The fusion site (2q13-14) — The single most important structural feature. At band 2q13, approximately 800 bp of head-to-head (TTAGGG)n telomeric repeat arrays mark the point where two ancestral chromosomes fused end-to-end (Ijdo et al., PNAS 199…

The vestigial centromere (2q21) — The inactivated centromere of the ancestral chromosome 2B sits at 2q21.3-q22.1, ~40 Mb distal to the fusion site. It contains remnant alpha-satellite DNA but has lost all centromeric function — no CENP-A binding, no k…

Segmental duplications at the fusion site — The 2q13-14 region is enriched in segmental duplications that show incomplete lineage sorting between human, chimpanzee, and gorilla, suggesting the fusion occurred close to the speciation events of African great apes…

Evolutionary History

The defining fusion — All great apes (chimpanzee, gorilla, orangutan) have 48 chromosomes (2n); humans have 46 (2n). The difference is entirely explained by the head-to-head fusion of ancestral chromosomes 2A and 2B. Chimpanzee chromosomes…

Timing — Molecular clock analyses using the degradation rate of the vestigial telomeric and centromeric sequences place the fusion event at approximately 0.74-4.5 million years ago. Recent T2T-based analyses suggest the fusion…

Deep Cuts

The fusion site is unremarkable — Perhaps the most surprising thing about the chromosome 2 fusion site is how boring it looks in functional genomic data. No genes, no enhancers, no DNase hypersensitivity peaks. The most consequential chromosomal rearr…

Titin variants and variant interpretation — TTN harbors so many rare missense variants in the general population that it is one of the most challenging genes in clinical genomics. The gnomAD database lists >10,000 unique TTN missense variants. Distinguishing pa…

The lactase-centromere coincidence — LCT sits just ~3 Mb from the vestigial centromere of the ancestral chromosome 2B. One of the strongest recent selective sweeps in human evolution occurred in the genomic shadow of one of evolution's most ancient scars…

§ Deep dive

The fusion site (2q13-14)The single most important structural feature. At band 2q13, approximately 800 bp of head-to-head (TTAGGG)n telomeric repeat arrays mark the point where two ancestral chromosomes fused end-to-end (Ijdo et al., PNAS 1991). The repeats are degenerate — roughly 158 TTAGGG-like units in inverted orientation — flanked by subtelomeric-like sequences that hybridize to multiple chromosome ends. This is the smoking gun of a telomere-telomere fusion.

The vestigial centromere (2q21)The inactivated centromere of the ancestral chromosome 2B sits at 2q21.3-q22.1, ~40 Mb distal to the fusion site. It contains remnant alpha-satellite DNA but has lost all centromeric function — no CENP-A binding, no kinetochore assembly. Its progressive degradation (alphoid repeats fragmented and diverged) provides a molecular clock for the fusion event.

Segmental duplications at the fusion siteThe 2q13-14 region is enriched in segmental duplications that show incomplete lineage sorting between human, chimpanzee, and gorilla, suggesting the fusion occurred close to the speciation events of African great apes. A 2025 study (Porubsky et al.) used T2T assemblies to show that these duplications predate the human-gorilla split.

Repeat content~44% interspersed repeats. The q arm is LINE-1 enriched (consistent with Giemsa-dark banding), while Alu elements cluster in the gene-dense regions of 2p. The fusion site itself is embedded in a complex repeat architecture including segmental duplications, processed pseudogenes, and satellite-derived sequences.

Fragile sitesIncludes FRA2A (2p11.2, rare folate-sensitive), FRA2B (2q13, common aphidicolin-sensitive — notably coinciding with the fusion site), FRA2C (2p24.2), FRA2D (2p16.2), and FRA2G (2q33). The co-localization of FRA2B with the fusion site raises the question of whether residual structural instability persists at this locus.