RESUMO
Cytosine methylation of DNA is a widespread modification of DNA that plays numerous critical roles. In the yeast Cryptococcus neoformans, CG methylation occurs in transposon-rich repeats and requires the DNA methyltransferase Dnmt5. We show that Dnmt5 displays exquisite maintenance-type specificity in vitro and in vivo and utilizes similar in vivo cofactors as the metazoan maintenance methylase Dnmt1. Remarkably, phylogenetic and functional analysis revealed that the ancestral species lost the gene for a de novo methylase, DnmtX, between 50-150 mya. We examined how methylation has persisted since the ancient loss of DnmtX. Experimental and comparative studies reveal efficient replication of methylation patterns in C. neoformans, rare stochastic methylation loss and gain events, and the action of natural selection. We propose that an epigenome has been propagated for >50 million years through a process analogous to Darwinian evolution of the genome.
Assuntos
Cryptococcus neoformans/genética , Metilação de DNA/genética , Metiltransferases/genética , Evolução Biológica , Cryptococcus neoformans/metabolismo , DNA/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA/fisiologia , Metilases de Modificação do DNA/genética , Elementos de DNA Transponíveis/genética , Epigenômica/métodos , Evolução Molecular , Genoma/genética , Metiltransferases/metabolismo , FilogeniaRESUMO
Cryptococcosis is a cosmopolitan fungal serious condition due to an encapsulated yeast Cryptococcus neoformans. This is the systemic fungal infection the most common in HIV infection. This yeast is present in the environment and its main entrance in the body is the respiratory tract. Its gravity is linked to its tropism for the central nervous system. It generally affects subjects with severe deficit of cellular immunity and in particular, patients living with HIV. The diagnosis of neuromeningeal cryptococcosis is based on the detection of encapsulated yeasts at microscopic examination of cerebrospinal fluid, the detection of capsular polysaccharide antigen in serum or cerebrospinal fluid, but especially on the culture. A staging is always essential. The prognosis is severe. The control of intracranial hypertension is a major element of prognosis.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS , Criptococose , Infecções por HIV , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/terapia , Coinfecção , Criptococose/complicações , Criptococose/diagnóstico , Criptococose/epidemiologia , Criptococose/terapia , Cryptococcus neoformans/isolamento & purificação , Cryptococcus neoformans/fisiologia , Diagnóstico Diferencial , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , HIV-1 , Humanos , PrognósticoRESUMO
Cryptocococcus neoformans is an encapsulated yeast that can cause life-threatening infections in immunocompromised patients. In this study, the genetic variability and epidemiological relationships of clinical and environmental isolates of C. neoformans from Busan, Korea, 2000~2005 were investigated. A total of 12 strains of C. neoformans, 7 clinical and 5 environmental isolates were analyzed by random amplified polymorphic DNA (RAPD) using three different primers and PCR-fingerprinting with a minisatellite-specific core sequence of phage M13. All strains belonged to C. neoformans serotype A and mating type MATa. Two different RAPD profiles (I and II) and a single pattern by M13 PCR-fingerprinting were identified. The major RAPD profile was pattern I (8 of 12 strains) and pattern II was identified from 2 clinical and 2 environmental strains, which clearly distinguished among isolates. Clinical strains with pattern II were isolated from the patients with HIV positive. Taken together, molecular patterns provide a good characterization of strains of C. neoformans as a heterogeneous group and epidemiological relationships in clinical and environmental strains.