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Early Diverging Fungus Mucor circinelloides Lacks Centromeric Histone CENP-A and Displays a Mosaic of Point and Regional Centromeres.

María Isabel Navarro-Mendoza | Carlos Pérez-Arques | Shweta Panchal | Francisco E Nicolás | Stephen J Mondo | Promit Ganguly | Jasmyn Pangilinan | Igor V Grigoriev | Joseph Heitman | Kaustuv Sanyal | Victoriano Garre
Current biology : CB | 2019

Centromeres are rapidly evolving across eukaryotes, despite performing a conserved function to ensure high-fidelity chromosome segregation. CENP-A chromatin is a hallmark of a functional centromere in most organisms. Due to its critical role in kinetochore architecture, the loss of CENP-A is tolerated in only a few organisms, many of which possess holocentric chromosomes. Here, we characterize the consequence of the loss of CENP-A in the fungal kingdom. Mucor circinelloides, an opportunistic human pathogen, lacks CENP-A along with the evolutionarily conserved CENP-C but assembles a monocentric chromosome with a localized kinetochore complex throughout the cell cycle. Mis12 and Dsn1, two conserved kinetochore proteins, were found to co-localize to a short region, one in each of nine large scaffolds, composed of an ∼200-bp AT-rich sequence followed by a centromere-specific conserved motif that echoes the structure of budding yeast point centromeres. Resembling fungal regional centromeres, these core centromere regions are embedded in large genomic expanses devoid of genes yet marked by Grem-LINE1s, a novel retrotransposable element silenced by the Dicer-dependent RNAi pathway. Our results suggest that these hybrid features of point and regional centromeres arose from the absence of CENP-A, thus defining novel mosaic centromeres in this early-diverging fungus.

Pubmed ID: 31679929

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI039115
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI050113
  • Agency: NIAID NIH HHS, United States
    Id: R37 AI039115

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