A new Nature study led by HHU Düsseldorf and MPIPZ Cologne reveals the process by which centromeres change their sequence rapidly over time. These structures are essential for cell division but paradoxically evolve rapidly and extensively whilst maintaining their core function. The University of Sheffield played a key role in the research, with Dr Lisa Smith and Professor Jurriaan Ton generating some of the plant lineages analysed, alongside collaborators from Tübingen, Karlsruhe, and Munich.
Every time a cell divides, its chromosomes must be distributed correctly between the two daughter cells. Central to this process is the centromere, a specialised region of the chromosome. The centromere serves as the attachment site for the cellular machinery that pulls the chromosomes apart.
Centromeres thus perform an essential function in cell division that emerged very early in eukaryotic evolution. Remarkably, although this function has been retained over almost two billion years of evolution, the DNA sequences underlying centromeres have evolved at an extraordinarily rapid rate. An international team led by Professor Dr Korbinian Schneeberger, head of the Institute of Crop Biology at HHU, has now discovered how relatively small mutations can give rise to the enormous differences between centromeres.
While the fundamental function of centromeres is highly conserved, their DNA sequences are not: centromeres can differ dramatically between species and even between individuals of the same species. This apparent contradiction is known in biology as the “centromere paradox” and raises the question of how a structure that has retained such an ancient function can contain DNA that changes so rapidly.
The research team used the model plant thale cress (Arabidopsis thaliana) to directly investigate the mutations that occur within the centromeres from one generation to the next. The study showed that centromeres exhibit a characteristic pattern of mutation: point mutations – changes affecting just a single nucleotide, essentially one “letter” of the genome – occur at an almost tenfold higher rate than in the chromosome arms. Insertions and deletions also occur frequently, typically involving hundreds to several thousand DNA letters.
These mutations are not random disruptions of the centromere. In Arabidopsis, centromeres consist largely of a basic DNA sequence approximately 178 letters in length that is repeated thousands of times. The newly identified insertions and deletions almost always added or removed complete copies of these repeat units, thereby maintaining the centromere’s repetitive architecture.
“Studying centromeres has long been a challenge due to their repetitive sequences” says Dr Lisa Smith of the University of Sheffield. “Recent improvements in DNA sequencing technologies allowed the first complete look at the chromosomal centromeres five years ago. This study goes further to compare centromeres from plants separated by a small number of generations, allowing the mutations within the centromeres to be identified.”
“Centromeres are far more dynamic than one might expect for a region of the genome with such an essential function,” says Xiao Dong, a doctoral researcher at the MPIPZ and first author of the study. “At the same time, the mutations are remarkably structured: they alter the centromere while preserving its basic repetitive organisation.”
Big patterns from small changes
The researchers were particularly interested in one of the most striking features of centromeres: their repetitive DNA is organised into vast blocks, which are sometimes millions of DNA letters in length, with repeats that are highly similar. These blocks can differ drastically between individuals. Professor Schneeberger, senior author of the study: “It was previously thought that structures of this size required large mutations or long-range rearrangements to form. Our study shows that this is not the case.”
The researchers demonstrated this through simulations in which they modelled the evolution of centromeres over many thousands of generations, using experimentally measured mutation rates and types. In the simulations, relatively small mutations, mostly affecting only a few thousand DNA letters, gradually generated large blocks comprising hundreds of thousands to millions of DNA letters that closely resembled the structures found in natural centromeres.
“This difference in scale is remarkable,” remarks Xiao Dong. “In natural centromeres, we can see vast patterns that extend over millions of DNA letters. They did not emerge as a result of similarly enormous changes, though, but rather through the accumulation of many relatively small mutations.”
“Since we began studying spontaneous mutation rates in plants almost 20 years ago, we have wondered whether different parts of the genome mutate in different ways,” says Professor Detlef Weigel from the Max Planck Institute for Biology in Tübingen. “This study shows that centromeres are indeed different. Their unusual mutational dynamics help explain why centromeres stand out so strikingly when we compare the genomes of different individuals and populations.”
Professor Schneeberger: “Our work connects two very different evolutionary scales: local mutations that occur from one generation to the next and the enormous differences between centromeres that have emerged over thousands of generations of evolution.”
The study was carried out by researchers from the Max Planck Institute for Plant Breeding Research in Cologne, the Max Planck Institute for Biology in Tübingen, The University of Sheffield, the Joseph Gottlieb Kölreuter Institute for Plant Sciences at Karlsruhe Institute of Technology (KIT), LMU Munich and Heinrich Heine University (HHU) Düsseldorf through its CEPLAS Cluster of Excellence
Original publication
Xiao Dong, Wen-Biao Jiao, Lara Goldkuhle, Fernando Rabanal, Samija Amar, Matthew T. Parker, José A Campoy, Yueqi Tao, Bruno Huettel, Jurriaan Ton, Lisa M. Smith, Holger Puchta, Detlef Weigel, and Korbinian Schneeberger. “The mutational dynamics of the Arabidopsis centromeres”, Nature (2026)
DOI: 10.1038/s41586-026-11046-w
[Link: https://www.nature.com/articles/s41586-026-11046-w]