拟南芥着丝粒的突变动力学

Centromeres are essential for faithful chromosome segregation during cell division. Yet despite their conserved function, many centromeres contain highly variable but internally remarkably homogenized tandem-repeat arrays1-5 whose evolutionary dynamics remain poorly understood. Here, using replicated genome assemblies of mutation accumulation lines, we define the centromere-specific mutation spectrum in Arabidopsis thaliana. We find that kilobase-sized insertion-deletion mutations (indels) occur frequently and consistently preserve tandem-repeat arrays by adding or removing only complete repeat units. Point mutations accumulate at an almost tenfold higher rate than elsewhere in the genome, probably driven by non-allelic gene conversion between closely linked repeat units. These findings suggest a central role for homology-directed DNA repair in centromere evolution, further supported by the accumulation of more frequent and longer tandem-repeat-preserving indels in Arabidopsis lines that are deficient in the anti-recombinase helicase RTEL1. Forward-in-time simulations parameterized with the observed mutation spectrum show that kilobase-sized indels and point mutations alone are sufficient to generate the megabase-sized homogenized repeat blocks characteristic of natural centromeres. Together, our results show that centromere evolution is driven by a distinct mutational spectrum shaped by homology-directed DNA repair, providing a quantitative framework for understanding how mutational processes generate and maintain the large-scale architecture of centromeric DNA.