RESUMEN
Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries. Here we present the genome of E. histolytica, which reveals a variety of metabolic adaptations shared with two other amitochondrial protist pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include reduction or elimination of most mitochondrial metabolic pathways and the use of oxidative stress enzymes generally associated with anaerobic prokaryotes. Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial genes into the E. histolytica genome, the effects of which centre on expanding aspects of E. histolytica's metabolic repertoire. The presence of these genes and the potential for novel metabolic pathways in E. histolytica may allow for the development of new chemotherapeutic agents. The genome encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence. Additional genome features include an abundance of tandemly repeated transfer-RNA-containing arrays, which may have a structural function in the genome. Analysis of the genome provides new insights into the workings and genome evolution of a major human pathogen.
Asunto(s)
Entamoeba histolytica/genética , Genoma de Protozoos , Parásitos/genética , Animales , Entamoeba histolytica/metabolismo , Entamoeba histolytica/patogenicidad , Evolución Molecular , Fermentación , Transferencia de Gen Horizontal/genética , Glucólisis , Estrés Oxidativo/genética , Parásitos/metabolismo , Parásitos/patogenicidad , Filogenia , Transducción de Señal , Virulencia/genéticaRESUMEN
We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the approximately 160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated in pathogenesis and phagocytosis of host proteins may exemplify adaptations of the parasite during its transition to a urogenital environment. The genome sequence predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria.
Asunto(s)
Genoma de Protozoos , Análisis de Secuencia de ADN , Trichomonas vaginalis/genética , Animales , Transporte Biológico/genética , Elementos Transponibles de ADN , ADN Protozoario/genética , Transferencia de Gen Horizontal , Genes Protozoarios , Humanos , Hidrógeno/metabolismo , Redes y Vías Metabólicas/genética , Datos de Secuencia Molecular , Familia de Multigenes , Orgánulos/metabolismo , Estrés Oxidativo/genética , Péptido Hidrolasas/genética , Péptido Hidrolasas/metabolismo , Proteínas Protozoarias/genética , Proteínas Protozoarias/fisiología , Procesamiento Postranscripcional del ARN , Secuencias Repetitivas de Ácidos Nucleicos , Enfermedades de Transmisión Sexual/parasitología , Tricomoniasis/parasitología , Tricomoniasis/transmisión , Trichomonas vaginalis/citología , Trichomonas vaginalis/metabolismo , Trichomonas vaginalis/patogenicidadRESUMEN
A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that-along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions-have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.
Asunto(s)
Genoma de Protozoos , Leishmania major/genética , Proteoma , Proteínas Protozoarias/genética , Trypanosoma brucei brucei/genética , Trypanosoma cruzi/genética , Animales , Evolución Biológica , Cromosomas/genética , Evolución Molecular , Transferencia de Gen Horizontal , Genes Protozoarios , Genómica , Leishmania major/química , Leishmania major/metabolismo , Datos de Secuencia Molecular , Familia de Multigenes , Mutación , Filogenia , Plastidios/genética , Proteínas Protozoarias/química , Proteínas Protozoarias/fisiología , Recombinación Genética , Retroelementos , Especificidad de la Especie , Simbiosis , Sintenía , Telómero/genética , Trypanosoma brucei brucei/química , Trypanosoma brucei brucei/metabolismo , Trypanosoma cruzi/química , Trypanosoma cruzi/metabolismoRESUMEN
African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.