Recombination between heterologous human acrocentric chromosomes

The short arms of the human acrocentric chromosomes 13, 14, 15, 21, and 22 share large homologous regions, including the ribosomal DNA repeats and extended segmental duplications (1,2). While the complete assembly of these regions in the Telomere-to-Telomere consortium’s (T2T) CHM13 provided a model of their homology (3), it remained unclear if these patterns were ancestral or maintained by ongoing recombination exchange. Here, we use pangenomic resources and methods to show that specific pseudo-homologous regions of the acrocentrics recombine. Considering an all-to-all comparison of the high-quality human pangenome from the Human Pangenome Reference Consortium (HPRC) (4), we find that contigs from all of the acrocentric short arms form a community similar to those formed by single chromosomes or the sex chromosome pair. A variation graph (5) constructed from centromere-spanning acrocentric contigs indicates the presence of pseudo-homologous regions where most contigs appear as recombinants of heterologous CHM13 acrocentrics. A diploid T2T assembly of a target sample cross-validates these patterns (6). On chromosomes 13, 14, 21, and 22, we observe lower levels of linkage disequilibrium in pseudo-homologous regions than in their short and long arms, indicating higher rates of recombination and/or a larger effective population size (7). The ubiquity of signals of heterologous recombination seen in the HPRC draft pangenome’s acrocentric assemblies suggests that this phenomenon is a basic feature of human cellular biology, providing sequence and population-based confirmation of hypotheses first developed cytogenetically fifty years ago (8).