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Complete Genome Sequence of the Apicomplexan, Cryptosporidium parvum (Abrahamsen et al., 2004)

This article describes the genome sequence of Cryptosporidium which lacks a mitochondrial genome and is thus completely dependent on the eukaryotic nucleus. Their conclusion is that it has lost its genome and its mitochondrion is degenerate, which is again a pity since it becomes difficult to see what their real data is and what they conjectured. 

Abstract: The apicomplexan Cryptosporidium parvum is an intestinal parasite that affects healthy humans and animals, and causes an unrelenting infection in immunocompromised individuals such as AIDS patients. We report the complete genome sequence of C. parvum, type II isolate. Genome analysis identifies extremely streamlined metabolic pathways and a reliance on the host for nutrients. In contrast to Plasmodium and Toxoplasma, the parasite lacks an apicoplast and its genome, and possesses a degenerate mitochondrion that has lost its genome. Several novel classes of cell-surface and secreted proteins with a potential role in host interactions and pathogenesis were also detected. Elucidation of the core metabolism, including enzymes with high similarities to bacterial and plant counterparts, opens new avenues for drug development.

Our sequence analysis indicates that Cryptosporidium, unlike Plasmodium and Toxoplasma, lacks both mitochondrion and apicoplast genomes. The overall completeness of the genome sequence, together with the fact that similar DNA extraction procedures used to isolate total genomic DNA from C. parvum efficiently yielded mitochondrion and apicoplast genomes from Eimeria sp. and Toxoplasma (6, 7), indicates that the absence of organellar genomes was unlikely to have been the result of methodological error. These conclusions are consistent with the absence of nuclear genes for the DNA replication and translation machinery characteristic of mitochondria and apicoplasts, and with the lack of mitochondrial or apicoplast targeting signals for tRNA synthetases.

Interestingly, the nuclear genome does not code for a number of enzymes, specifically those for oxidative phosphorylation and therefore makes it a good candidate for a primitive or precursor mitochondrion, see also its metabolism.

A number of putative mitochondrial proteins were identified, including components of a mitochondrial protein import apparatus, chaperones, uncoupling proteins, and solute translocators (table S1). However, the genome does not encode any Krebs cycle enzymes, nor the components constituting the mitochondrial complexes I to IV; this finding indicates that the parasite does not rely on complete oxidation and respiratory chains for synthesizing adenosine triphosphate (ATP). Similar to Plasmodium, no orthologs for the (gamma delta or epsilon) subunits or the c subunit of the F0 proton channel were detected (whereas all subunits were found for a V-type ATPase).

Cryptosporidium, like Eimeria (8) and Plasmodium, possesses a pyridine nucleotide transhydrogenase integral membrane protein that may couple reduced nicotinamide adenine dinucleotide (NADH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) redox to proton translocation across the inner mitochondrial membrane. Unlike Plasmodium, the parasite has two copies of the pyridine nucleotide transhydrogenase gene. Also present is a likely mitochondrial membrane–associated, cyanide-resistant alternative oxidase (AOX) that catalyzes the reduction of molecular oxygen by ubiquinol to produce H2O, but not superoxide or H2O2. Several genes were identified as involved in biogenesis of iron-sulfur [Fe-S] complexes with potential mitochondrial targeting signals (e.g., nifS, nifU, frataxin, and ferredoxin), supporting the presence of a limited electron flux in the mitochondrial remnant (table S2).

C. parvum metabolism is greatly streamlined relative to that of Plasmodium, and in certain ways it is reminiscent of that of another obligate eukaryotic parasite, the microsporidian Encephalitozoon. The degeneration of the mitochondrion and associated metabolic capabilities suggests that the parasite largely relies on glycolysis for energy production. The parasite is capable of uptake and catabolism of monosugars (e.g., glucose and fructose) as well as synthesis, storage, and catabolism of polysaccharides such as trehalose and amylopectin. Like many anaerobic organisms, it economizes ATP through the use of pyrophosphate-dependent phosphofructokinases. The conversion of pyruvate to acetyl–coenzyme A (CoA) is catalyzed by an atypical pyruvate-NADPH oxidoreductase (CpPNO) that contains an N-terminal pyruvate–ferredoxin oxidoreductase (PFO) domain fused with a C-terminal NADPH–cytochrome P450 reductase domain (CPR). Such a PFO-CPR fusion has previously been observed only in the euglenozoan protist Euglena gracilis (12). Acetyl-CoA can be converted to malonyl-CoA, an important precursor for fatty acid and polyketide biosynthesis. Glycolysis leads to several possible organic end products, including lactate, acetate, and ethanol. The production of acetate from acetyl-CoA may be economically beneficial to the parasite via coupling with ATP production.

Ethanol is potentially produced via two independent pathways: (i) from the combination of pyruvate decarboxylase and alcohol dehydrogenase, or (ii) from acetyl-CoA by means of a bifunctional dehydrogenase (adhE) with acetaldehyde and alcohol dehydrogenase activities; adhE first converts acetyl-CoA to acetaldehyde and then reduces the latter to ethanol


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