An essential region of our chromosomes changes far more rapidly than one might imagine.
A large-scale analysis of human centromeres shows that their DNA mutates on average 16.4 times faster than the neighboring regions studied. Yet this part of the chromosome must function properly during every cell division.
The centromere is the constricted region often seen in chromosome diagrams. When a cell divides, a structure called the kinetochore forms there. It serves as an attachment point for the fibers that pull chromosome copies toward the two future cells.
These regions are difficult to read using conventional sequencing methods. Their DNA contains very long series of repeated motifs, which is like reconstructing a puzzle made up of thousands of nearly identical pieces. Recent techniques that read large DNA fragments now make it possible to create much more complete maps of them.
Shenghan Gao and his colleagues assembled and studied 2,110 centromeres from individuals representing five continents and 28 population groups. They identified 226 previously unknown large variants and 1,870 new variants in the long repeated sequences characteristic of these regions.
The diversity also concerns their size. On chromosome 6, the authors observed a difference of up to 21.5-fold between the smallest and largest assemblies. Chromosome 18, meanwhile, showed a maximum difference of 6.3 million base pairs, the units that make up the DNA sequence.
The researchers then estimated how quickly these sequences change over the course of generations. On average, the repeated regions of centromeres reach 4.07 × 10⁻⁷ mutations per base pair per generation. This rate is 16.4 times higher than that of the unique portions of DNA located around the centromeres.
Not all chromosomes follow the same pace. The centromere of the Y chromosome has the lowest rate measured, while that of chromosome 1 has the highest. The difference between the two reaches a factor of 20.1. The authors also checked their estimates using a family of 28 people followed over four generations.
This mapping now provides access to genomic regions that had long remained incomplete.