Assuntos
Pulmão , Pneumocystis , Pneumonia por Pneumocystis , Animais , Humanos , Pulmão/metabolismo , Pulmão/microbiologia , Pulmão/patologia , Pneumocystis/classificação , Pneumocystis/metabolismo , Pneumocystis/patogenicidade , Pneumonia por Pneumocystis/metabolismo , Pneumonia por Pneumocystis/microbiologia , Pneumonia por Pneumocystis/patologia , Especificidade da EspécieRESUMO
Centromeres are genomic regions that coordinate accurate chromosomal segregation during mitosis and meiosis. Yet, despite their essential function, centromeres evolve rapidly across eukaryotes. Centromeres are often the sites of chromosomal breaks which contribute to genome shuffling and promote speciation by inhibiting gene flow. How centromeres form in strongly host-adapted fungal pathogens has yet to be investigated. Here, we characterized the centromere structures in closely related species of mammalian-specific pathogens of the fungal phylum of Ascomycota. Methods allowing reliable continuous culture of Pneumocystis species do not currently exist, precluding genetic manipulation. CENP-A, a variant of histone H3, is the epigenetic marker that defines centromeres in most eukaryotes. Using heterologous complementation, we show that the Pneumocystis CENP-A ortholog is functionally equivalent to CENP-ACnp1 of Schizosaccharomyces pombe. Using organisms from a short-term in vitro culture or infected animal models and ChIP-seq, we identified centromeres in three Pneumocystis species that diverged ~100 million years ago. Each species has a unique short regional centromere (< 10kb) flanked by heterochromatin in 16-17 monocentric chromosomes. They span active genes and lack conserved DNA sequence motifs and repeats. CENP-C, a scaffold protein that links the inner centromere to the kinetochore appears dispensable in one species, suggesting a kinetochore rewiring. Despite the loss of DNA methyltransferases, 5-methylcytosine DNA methylation occurs in these species, though not related to centromere function. These features suggest an epigenetic specification of centromere function.
RESUMO
Far more biodiversity exists in Fungi than has been described, or could be described in several lifetimes, given current rates of species discovery. Although this problem is widespread taxonomically, our knowledge of animal-associated fungi is especially lacking. Fungi in the genus Pneumocystis are obligate inhabitants of mammal lungs, and they have been detected in a phylogenetically diverse array of species representing many major mammal lineages. The hypothesis that Pneumocystis cospeciate with their mammalian hosts suggests that thousands of Pneumocystis species may exist, potentially equal to the number of mammal species. However, only six species have been described, and the true correspondence of Pneumocystis diversity to host species boundaries is unclear. Here, we use molecular species delimitation to estimate the boundaries of Pneumocystis species sampled from 55 mammal species representing eight orders. Our results suggest that Pneumocystis species often colonize several closely related mammals, especially those in the same genus. Using the newly estimated ratio of fungal to host diversity, we estimate ≈4600 to 6250 Pneumocystis species inhabit the 6495 currently recognized extant mammal species. Additionally, we review the literature and find that only 240 (~3.7%) mammal species have been screened for Pneumocystis, and many detected Pneumocystis lineages are not represented by any genetic data. Although crude, our findings challenge the dominant perspective of strict specificity of Pneumocystis to their mammal hosts and highlight an abundance of undescribed diversity.