Spatial inter-centromeric interactions facilitated the emergence of evolutionary new centromeres.

Abstract

Centromeres of <i>Candida albicans</i> form on unique and different DNA sequences but a closely related species, <i>Candida tropicalis</i>, possesses homogenized inverted repeat (HIR)-associated centromeres. To investigate the mechanism of centromere type transition, we improved the fragmented genome assembly and constructed a chromosome-level genome assembly of <i>C. tropicalis</i> by employing PacBio sequencing, chromosome conformation capture sequencing (3C-seq), chromoblot, and genetic analysis of engineered aneuploid strains. Further, we analyzed the 3D genome organization using 3C-seq data, which revealed spatial proximity among the centromeres as well as telomeres of seven chromosomes in <i>C. tropicalis</i>. Intriguingly, we observed evidence of inter-centromeric translocations in the common ancestor of <i>C. albicans</i> and <i>C. tropicalis</i>. Identification of putative centromeres in closely related <i>Candida sojae</i>, <i>Candida viswanathii</i> and <i>Candida parapsilosis</i> indicates loss of ancestral HIR-associated centromeres and establishment of evolutionary new centromeres (ENCs) in <i>C. albicans</i>. We propose that spatial proximity of the homologous centromere DNA sequences facilitated karyotype rearrangements and centromere type transitions in human pathogenic yeasts of the CUG-Ser1 clade.