Abstract
The centromere, on which kinetochore proteins assemble, ensures precise chromosome segregation. Centromeres are largely specified by the histone H3 variant CENP-A (also known as Cse4 in yeasts). Structurally, centromere DNA sequences are highly diverse in nature. However, the evolutionary consequence of these structural diversities on de novo CENP-A chromatin formation remains elusive. Here, we report the identification of centromeres, as the binding sites of four evolutionarily conserved kinetochore proteins, in the human pathogenic budding yeast Candida tropicalis. Each of the seven centromeres comprises a 2 to 5 kb non-repetitive mid core flanked by 2 to 5 kb inverted repeats. The repeat-associated centromeres of C. tropicalis all share a high degree of sequence conservation with each other and are strikingly diverged from the unique and mostly non-repetitive centromeres of related Candida species—Candida albicans, Candida dubliniensis, and Candida lusitaniae. Using a plasmid-based assay, we further demonstrate that pericentric inverted repeats and the underlying DNA sequence provide a structural determinant in CENP-A recruitment in C. tropicalis, as opposed to epigenetically regulated CENP-A loading at centromeres in C. albicans. Thus, the centromere structure and its influence on de novo CENP-A recruitment has been significantly rewired in closely related Candida species. Strikingly, the centromere structural properties along with role of pericentric repeats in de novo CENP-A loading in C. tropicalis are more reminiscent to those of the distantly related fission yeast Schizosaccharomyces pombe. Taken together, we demonstrate, for the first time, fission yeast-like repeat-associated centromeres in an ascomycetous budding yeast.
Highlights
The high fidelity segregation of replicated chromosomes to daughter cells during cell division is essential in maintaining genome integrity
Centromere DNA sequences are rapidly evolving in fungi, plants, and animals
Centromere DNA sequences in fungi can be unique in each chromosome or share conserved features such as motifs for sequence specific protein binding, pericentric repeats, or transposon-rich elements
Summary
The high fidelity segregation of replicated chromosomes to daughter cells during cell division is essential in maintaining genome integrity It is achieved by a dynamic and well-coordinated kinetochore-microtubule interaction on a specialized chromosomal element, known as the centromere. The centromere DNA shows rapid diversification in its sequence, length, and the organization of sequence elements across different species [1,2,3]. The large regional centromeres of most plants (reviewed in [5, 6]) and animals (reviewed in [7]) are composed of an array of either repetitive sequences or transposable elements. The centromeres in these organisms lack any sequence conservation shared among different chromosomes in the same species. The driving force enabling the evolution of centromeres with such remarkable diversity both in the DNA sequence as well as structure, rather than a common optimized centromere configuration, across eukaryotes remains an enigma [1]
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