Runaway evolution of telomeres in ascomycetous yeasts was accompanied by the replacement of ancestral telomeric proteins.

Telomeres are crucial parts of eukaryotic chromosomes, contributing to DNA replication, chromosome segregation, and genome stability. While in most phylogenetic lineages, telomere-maintenance systems are conserved, ascomycetous yeasts exhibit a high degree of variability in telomeric repeats and the associated proteins. The determinants that enabled this divergent evolutionary process, however, have been unclear. Here, we show that DNA-binding properties of yeast telomere-binding proteins (TBPs) support the scenario where the gradual divergence of telomeric repeats led to their replacement. We analyzed the DNA-protein interactions between Tay1p from Yarrowia lipolytica, Rap1p from Saccharomyces cerevisiae, and Taz1p from Schizosaccharomyces pombe and a set of telomeric repeats from several yeast species and delineated how the ancestral (Tay1p-like) TBPs were replaced by Rap1p (in budding yeasts) or Taz1p (in fission yeasts). We also postulate two different driving forces for these replacements: (i) Tay1p-to-Rap1p transition appears to be driven by differences in sequence preferences of Tay1p and Rap1p, while (ii) Taz1p became the principal TBP in fission yeast presumably due to its DNA-binding flexibility. Together, our results suggest that in telomeric DNA-protein complexes, the replacement of protein component triggered by the initial variation in DNA sequence space opens the door to further divergence in a runaway-style evolution.