Global Survey Reveals Vast Human Centromere Diversity and Rapid Evolution

The researchers leveraged recent telomere-to-telomere assemblies and a custom pipeline called AssemblyRepairer to correct errors and produce a set of 2,110 fully resolved centromeres from 65 globally diverse genomes. Bioinformatic mapping (CenMAP) revealed 226 distinct centromere haplotypes and nearly 2,000 new α-satellite higher-order repeat variants, many of which differ from the reference CHM13 genome. About 6% of the centromeres host two functional kinetochores (di-kinetochores) and less than 1% have three, a pattern.

Phylogenetic comparison with 5,747 centromeres from the Human Pangenome Reference Consortium showed mutation rates varying twenty-fold among chromosomes, with the kinetochore region mutating 1.8 times faster than adjacent arrays, and some haplotypes bearing archaic hominin introgression. A rare recombination event between chromosomes 13 and 22 created a hybrid centromere, illustrating structural plasticity. The authors propose an ‘arms-race’ model where homogeneous α-satellite stretches attract kinetochore formation, become mutation hotspots, and drive continual centromere evolution, with implications for chromosome segregation fidelity and human disease.