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PubMed2005

The "domino theory" of gene death: gradual and mass gene extinction events in three lineages of obligate symbiotic bacterial pathogens.

During the adaptation of an organism to a parasitic lifestyle, various gene functions may be rendered superfluous due to the fact that the host may supply these needs. As a consequence, obligate symbiotic bacterial pathogens tend to undergo reductive genomic evolution through gene death (nonfunctionalization or pseudogenization) and deletion. Here, we examine the evolutionary sequence of gene-death events during the process of genome miniaturization in three bacterial species that have experienced extensive genome reduction: Mycobacterium leprae, Shigella flexneri, and Salmonella typhi. We infer that in all three lineages, the distribution of functional categories is similar in pseudogenes and genes but different from that of absent genes. Based on an analysis of evolutionary distances, we propose a two-step "domino effect" model for reductive genome evolution. The process starts with a gradual gene-by-gene-death sequence of events. Eventually, a crucial gene within a complex pathway or network is rendered nonfunctional triggering a "mass gene extinction" of the dependent genes. In contrast to published reports according to which genes belonging to certain functional categories are prone to nonfunctionalization more frequently and earlier than genes belonging to other functional categories, we could discern no characteristic regularity in the temporal order of function loss.

Bacteria↗

PubMed1996

Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae.

The entire genome of the bacterium Mycoplasma pneumoniae M129 has been sequenced. It has a size of 816,394 base pairs with an average G+C content of 40.0 mol%. We predict 677 open reading frames (ORFs) and 39 genes coding for various RNA species. Of the predicted ORFs, 75.9% showed significant similarity to genes/proteins of other organisms while only 9.9% did not reveal any significant similarity to gene sequences in databases. This permitted us tentatively to assign a functional classification to a large number of ORFs and to deduce the biochemical and physiological properties of this bacterium. The reduction of the genome size of M. pneumoniae during its reductive evolution from ancestral bacteria can be explained by the loss of complete anabolic (e.g. no amino acid synthesis) and metabolic pathways. Therefore, M. pneumoniae depends in nature on an obligate parasitic lifestyle which requires the provision of exogenous essential metabolites. All the major classes of cellular processes and metabolic pathways are briefly described. For a number of activities/functions present in M. pneumoniae according to experimental evidence, the corresponding genes could not be identified by similarity search. For instance we failed to identify genes/proteins involved in motility, chemotaxis and management of oxidative stress.

Base Sequence↗

PubMed1998

RNA editing in the free-living bodonid Bodo saltans.

In parasitic kinetoplastid protozoa, mitochondrial (mt) mRNAs are post-transcriptionally edited by insertion and deletion of uridylate residues, the information being provided by guide (g) RNAs. In order to further explore the role and evolutionary history of this process, we searched for editing in mt RNAs of the free-living bodonid Bodo saltans. We found extensive editing in the transcript for NADH dehydrogenase (ND) subunit 5, which is unedited in trypanosomatids. In contrast, B.saltans cytochrome c oxidase (cox) subunit 2 and maxicircle unidentified reading frame (MURF) 2 RNAs display limited editing in the same regions as their trypanosomatid counterparts. A putative intramolecular cox2 gRNA and the gene for gMURF2-I directing the insertion of only one U in the 5' editing domain of MURF2 RNA, are conserved in B.saltans. This lends (further) evolutionary support to the proposed role of these sequences as gRNAs. Phylogenetic analysis showed that B.saltans is more closely related to trypanosomatids than the cryptobiids Trypanoplasma borreli and Cryptobia helicis, in line with the trypanosomatid-like cox2 and MURF2 RNA editing patterns. Nevertheless, other features like the apparent absence of a catenated mtDNA network, are shared with bodonid and cryptobiid species. ND5 RNA editing may represent yet another example of editing 'on the way out' during kinetoplastid evolution, but in view of the fact that cox2 RNA is unedited in T. borreli and C.helicis, we infer that the editing of this RNA may have arisen relatively recently. Our results provide the first examples of RNA editing in a free-living kinetoplastid, indicating that there is no direct link between U-insertion/deletion editing and a parasitic lifestyle.

Amino Acid Sequence↗

PubMed2004

Phylogenetic position of the Pentastomida and (pan)crustacean relationships.

Pentastomids are a small group of vermiform animals with unique morphology and parasitic lifestyle. They are generally recognized as being related to the Arthropoda; however, the nature of this relationship is controversial. We have determined the complete sequence of the mitochondrial DNA (mtDNA) of the pentastomid Armillifer armillatus and complete or nearly complete mtDNA sequences from representatives of four previously unsampled groups of Crustacea: Remipedia (Speleonectes tulumensis), Cephalocarida (Hutchinsoniella macracantha), Cirripedia (Pollicipes polymerus) and Branchiura (Argulus americanus). Analyses of the mtDNA gene arrangements and sequences determined in this study indicate unambiguously that pentastomids are a group of modified crustaceans probably related to branchiurans. In addition, gene arrangement comparisons strongly support an unforeseen assemblage of pentastomids with maxillopod and cephalocarid crustaceans, to the exclusion of remipedes, branchiopods, malacostracans and hexapods.

Animals↗

PubMed2005

Evaluation of amplified rDNA restriction analysis (ARDRA) for the identification of Mycoplasma species.

BACKGROUND: Mycoplasmas are present worldwide in a large number of animal hosts. Due to their small genome and parasitic lifestyle, Mycoplasma spp. require complex isolation media. Nevertheless, already over 100 different species have been identified and characterized and their number increases as more hosts are sampled. We studied the applicability of amplified rDNA restriction analysis (ARDRA) for the identification of all 116 acknowledged Mycoplasma species and subspecies. METHODS: Based upon available 16S rDNA sequences, we calculated and compared theoretical ARDRA profiles. To check the validity of these theoretically calculated profiles, we performed ARDRA on 60 strains of 27 different species and subspecies of the genus Mycoplasma. RESULTS: In silico digestion with the restriction endonuclease AluI (AG--CT) was found to be most discriminative and generated from 3 to 13 fragments depending on the Mycoplasma species. Although 73 Mycoplasma species could be differentiated using AluI, other species gave undistinguishable patterns. For these, an additional restriction digestion, typically with BfaI (C--TAG) or HpyF10VI (GCNNNNN--NNGC), was needed for a final identification. All in vitro obtained restriction profiles were in accordance with the calculated fragments based on only one 16S rDNA sequence, except for two isolates of M. columbinum and two isolates of the M. mycoides cluster, for which correct ARDRA profiles were only obtained if the sequences of both rrn operons were taken into account. CONCLUSION: Theoretically, restriction digestion of the amplified rDNA was found to enable differentiation of all described Mycoplasma species and this could be confirmed by application of ARDRA on a total of 27 species and subspecies.

Animals↗

PubMed2000

Borrelia genomes in the year 2000.

All analyzed members of the spirochete genus Borrelia contain a linear chromosome about 910 kbp long. The complete sequence of the B. burgdorferi B31 genome predicts that its chromosome carries essentially all of this organism's housekeeping genes. In accordance with these bacterial species' obligatory parasitic lifestyle, its genes encode enzymes that are capable of only a minimal metabolism, in which all nucleotides, amino acids, fatty acids and enzyme cofactors must be scavenged from the host. In addition to the chromosome, all Borrelia isolates examined carry multiple linear and circular plasmids with lengths between 5 and 200 kbp. The plasmids, which account for over 600 kbp in isolate B31, carry very few genes with homology to genes outside of the Borrelia genus. But they do carry numerous predicted lipoprotein genes, many of which are have been shown to be or are expected to be outer surface proteins. Ten of the linear plasmids have strikingly low protein coding potential for bacterial DNA. These plasmids have enjoyed numerous past duplicative rearrangements, which have resulted in the presence of a substantial fraction of the DNA that appears to be currently undergoing mutational decay, presumably because it is no longer under selection for function.

Borrelia↗

PubMed1994

Trypanosomatid protozoa provide paradigms of eukaryotic biology.

Over the last 10 years, trypanosomatid protozoa have been the subject of intense investigation particularly focusing on their parasitic lifestyle and their intriguing and novel cell properties. These studies have furthered our understanding of the physiology and functioning of these cells and have identified a large number of biochemical and metabolic peculiarities, including mitochondrial function, enzymatic compartmentalization, and gene expression. This review focuses on the mode of gene expression and highlights areas of trypanosome research that have provided paradigms of eukaryotic biology.

Animals↗

PubMed2001

Endocytosis in different lifestyles of protozoan parasitism: role in nutrient uptake with special reference to Toxoplasma gondii.

A fundamental property of any eukaryotic cell is endocytosis, that is the ability to take up external fluid, solutes and particulate matter into membrane-bound intracellular vesicles by various mechanisms. Toxoplasma gondii is an intracellular protozoan parasite of the phylum Apicomplexa with a wide geographical and host range distribution. Significant progress in studying the cell biology of this parasite has been accomplished over the last few years. Only recently endocytic compartments and endocytic trafficking have come to a closer dissection in T. gondii. In this review, we discuss the evidence for an endocytic compartment and present a model for an endocytic pathway in Toxoplasma against a background of endocytosis in kinetoplastida and the extensive insights gained from mammalian and yeast cells.

Animals↗

PubMed2001

The insect endosymbiont Sodalis glossinidius utilizes a type III secretion system for cell invasion.

Sodalis glossinidius is a maternally transmitted secondary endosymbiont residing intracellularly in tissues of the tsetse flies, Glossina spp. In this study, we have used Tn5 mutagenesis and a negative selection procedure to derive a S. glossinidius mutant that is incapable of invading insect cells in vitro and is aposymbiotic when microinjected into tsetse. This mutant strain harbors Tn5 integrated into a chromosomal gene sharing high sequence identity with a type III secretion system invasion gene (invC) previously identified in Salmonella enterica. With the use of degenerate PCR, we have amplified a further six Sodalis inv/spa genes sharing high sequence identity with type III secretion system genes encoded by Salmonella pathogenicity island 1. Phylogenetic reconstructions based on the inv/spa genes of Sodalis and other members of the family Enterobacteriaceae have consistently identified a well-supported clade containing Sodalis and the enteric pathogens Shigella and Salmonella. These results suggest that Sodalis may have evolved from an ancestor with a parasitic intracellular lifestyle, possibly a latter-day entomopathogen. These observations lend credence to a hypothesis suggesting that vertically transmitted mutualistic endosymbionts evolve from horizontally transmitted parasites through a parasitism-mutualism continuum.

Aedes↗

PubMed2003

Complete genome sequence of the Q-fever pathogen Coxiella burnetii.

The 1,995,275-bp genome of Coxiella burnetii, Nine Mile phase I RSA493, a highly virulent zoonotic pathogen and category B bioterrorism agent, was sequenced by the random shotgun method. This bacterium is an obligate intracellular acidophile that is highly adapted for life within the eukaryotic phagolysosome. Genome analysis revealed many genes with potential roles in adhesion, invasion, intracellular trafficking, host-cell modulation, and detoxification. A previously uncharacterized 13-member family of ankyrin repeat-containing proteins is implicated in the pathogenesis of this organism. Although the lifestyle and parasitic strategies of C. burnetii resemble that of Rickettsiae and Chlamydiae, their genome architectures differ considerably in terms of presence of mobile elements, extent of genome reduction, metabolic capabilities, and transporter profiles. The presence of 83 pseudogenes displays an ongoing process of gene degradation. Unlike other obligate intracellular bacteria, 32 insertion sequences are found dispersed in the chromosome, indicating some plasticity in the C. burnetii genome. These analyses suggest that the obligate intracellular lifestyle of C. burnetii may be a relatively recent innovation.

Bacterial Adhesion↗

PubMed2004

Lifestyle alternatives for rhizobia: mutualism, parasitism, and forgoing symbiosis.

Strains of rhizobia within a single species can have three different genetically determined strategies. Mutualistic rhizobia provide their legume hosts with nitrogen. Parasitic rhizobia infect legumes, but fix little or no nitrogen. Nonsymbiotic strains are unable to infect legumes at all. Why have rhizobium strains with one of these three strategies not displaced the others? A symbiotic (mutualistic or parasitic) rhizobium that succeeds in founding a nodule may produce many millions of descendants. The chances of success can be so low, however, that nonsymbiotic rhizobia can have greater reproductive success. Legume sanctions against nodules that fix little or no nitrogen favor more mutualistic strains, but parasitic strains that use plant resources only for their own reproduction may do well when they share nodules with mutualistic strains.

Alphaproteobacteria↗

PubMed2005

Signal transduction in larval trematodes: putative systems associated with regulating larval motility and behaviour.

The multi-host lifestyle of parasitic trematodes necessitates their ability to communicate with their external environment in order to invade and navigate within their hosts' internal environment. Through recent EST and genome sequencing efforts, it has become clear that members of the Trematoda possess many of the elaborate signal transduction systems that have been delineated in other invertebrate model systems like Drosophila melanogaster and Caenorhabditis elegans. Gene homologues representing several well-described signal receptor families including receptor tyrosine kinases, receptor serine tyrosine kinases, G protein-coupled receptors and elements of their downstream signalling systems have been identified in larval trematodes. A majority of this work has focused on the blood flukes, Schistosoma spp. and therefore represents a narrow sampling of the diverse digenean helminth taxon. Despite this fact and given the substantial evidence supporting the existence of such signalling systems, the question then becomes, how are these systems employed by larval trematodes to aid them in interpreting signals received from their immediate environment to initiate appropriate responses in cells and tissues comprising the developing parasite stages? High-throughput, genome-wide analysis tools now allow us to begin to functionally characterize genes differentially expressed throughout the development of trematode larvae. Investigation of the systems used by these parasites to receive and transduce external signals may facilitate the creation of technologies for achieving control of intramolluscan schistosome infections and also continue to yield valuable insights into the basic mechanisms regulating motility and behaviour in this important group of helminths.

Animals↗

PubMed1992

The p53 gene expression and its developmental regulation in schistosomes.

We have studied the gene expression, especially of the oncoproteins, and its regulation in schistosomes. Schistosomes have a complex life cycle with a defined dimorphic lifestyle. The parasite are so far unique in biology in expressing oncogene products in their adult stage. In order to characterize the expression and developmental regulation, a lambda gt 11 cDNA library and lambda EMBL4 genomic DNA library of each growth stage of Schistosoma mansoni and S. japonicum was constructed, and was screened with various monoclonal antibodies against oncogene products. One positive plaque reacted to anti-p53 antibody (Ab-2, Oncogene Science, Inc.) was further analyzed. This fusion protein was about 120 KDa in molecular weights, and expressed as 1.4 Kb RNA in the adult stage. P53 gene is well-known as the negative regulator of the cell cycle, and the mutations in the gene are turning out to be the most common genetic alterations in human cancers. The comparison of the gene structure among species and stages were being conducted. Chromosome structures, C-band formation, and the results of in situ hybridization using the phage probe would be discussed.

Animals↗

PubMed2005

The Wolbachia genome of Brugia malayi: endosymbiont evolution within a human pathogenic nematode.

Complete genome DNA sequence and analysis is presented for Wolbachia, the obligate alpha-proteobacterial endosymbiont required for fertility and survival of the human filarial parasitic nematode Brugia malayi. Although, quantitatively, the genome is even more degraded than those of closely related Rickettsia species, Wolbachia has retained more intact metabolic pathways. The ability to provide riboflavin, flavin adenine dinucleotide, heme, and nucleotides is likely to be Wolbachia's principal contribution to the mutualistic relationship, whereas the host nematode likely supplies amino acids required for Wolbachia growth. Genome comparison of the Wolbachia endosymbiont of B. malayi (wBm) with the Wolbachia endosymbiont of Drosophila melanogaster (wMel) shows that they share similar metabolic trends, although their genomes show a high degree of genome shuffling. In contrast to wMel, wBm contains no prophage and has a reduced level of repeated DNA. Both Wolbachia have lost a considerable number of membrane biogenesis genes that apparently make them unable to synthesize lipid A, the usual component of proteobacterial membranes. However, differences in their peptidoglycan structures may reflect the mutualistic lifestyle of wBm in contrast to the parasitic lifestyle of wMel. The smaller genome size of wBm, relative to wMel, may reflect the loss of genes required for infecting host cells and avoiding host defense systems. Analysis of this first sequenced endosymbiont genome from a filarial nematode provides insight into endosymbiont evolution and additionally provides new potential targets for elimination of cutaneous and lymphatic human filarial disease.

Animals↗

PubMed2003

Glutathione--functions and metabolism in the malarial parasite Plasmodium falciparum.

When present as a trophozoite in human erythrocytes, the malarial parasite Plasmodium falciparum exhibits an intense glutathione metabolism. Glutathione plays a role not only in antioxidative defense and in maintaining the reducing environment of the cytosol. Many of the known glutathione-dependent processes are directly related to the specific lifestyle of the parasite. Reduced glutathione (GSH) supports rapid cell growth by providing electrons for deoxyribonucleotide synthesis and it takes part in detoxifying heme, a product of hemoglobin digestion. Free radicals generated in the parasite can be scavenged in reaction sequences involving the thiyl radical GS* as well as the thiolate GS-. As a substrate of glutathione S-transferase, glutathione is conjugated to non-degradable compounds including antimalarial drugs. Furthermore, it is the coenzyme of the glyoxalase system which detoxifies methylglyoxal, a byproduct of the intense glycolysis taking place in the trophozoite. Proteins involved in GSH-dependent processes include glutathione reductase, glutaredoxins, glyoxalase I and II, glutathione S-transferases, and thioredoxins. These proteins, as well as the ATP-dependent enzymes of glutathione synthesis, are studied as factors in the pathophysiology of malaria but also as potential drug targets. Methylene blue, an inhibitor of the structurally known P. falciparum glutathione reductase, appears to be a promising antimalarial medication when given in combination with chloroquine.

Algorithms↗

PubMed2001

Where are the pseudogenes in bacterial genomes?

Most bacterial genomes have very few pseudogenes; notable exceptions include the genomes of the intracellular parasites Rickettsia prowazekii and Mycobacterium leprae. As DNA can be introduced into microbial genomes in many ways, the compact nature of these genomes suggests that the rate of DNA influx is balanced by the rate of DNA deletion. We propose that the influx of dangerous genetic elements such as transposons and bacteriophages selects for the maintenance of relatively high deletion rates in most bacteria; the sheltered lifestyle of intracellular parasites removes this threat, leading to reduced deletion rates and larger pseudogene loads.

Bacteriophages↗

PubMedDate not supplied

[Intestinal parasite infections and schistosomiasis in a poor urban area, in townships of the sugar cane belt and in villages of the semi-arid area of North-East Brazil].

We determined the prevalence of intestinal parasite infections between 1993 and 1998 in the populations of a poor quarter of Recife (Pernambuco), in two townships in the sugar cane belt and in three villages of the semi-arid area far from the coast. Intestinal schistosomiasis was present in the sugar-growing area but was not observed in the populations inland that use dams to provide irrigation and fishing. Ascaris was very common in the city and the sugar cane belt and large numbers of hookworms were observed, especially in the sugar-growing area. These nematodes were very rare in the semi-arid area. This distribution probably results from both climatic conditions and human behavior. The high frequency of Amoeba cysts demonstrates that the peasants, farmers and fisherman living in these areas have poor hygiene practices. There are probably many, complex relationships between education, income, lifestyle and intestinal parasite infections.

Adult↗

PubMed2006

Parasites dominate food web links.

Parasitism is the most common animal lifestyle, yet food webs rarely include parasites. The few earlier studies have indicated that including parasites leads to obvious increases in species richness, number of links, and food chain length. A less obvious result was that adding parasites slightly reduced connectance, a key metric considered to affect food web stability. However, reported reductions in connectance after the addition of parasites resulted from an inappropriate calculation. Two alternative corrective approaches applied to four published studies yield an opposite result: parasites increase connectance, sometimes dramatically. In addition, we find that parasites can greatly affect other food web statistics, such as nestedness (asymmetry of interactions), chain length, and linkage density. Furthermore, whereas most food webs find that top trophic levels are least vulnerable to natural enemies, the inclusion of parasites revealed that mid-trophic levels, not low trophic levels, suffered the highest vulnerability to natural enemies. These results show that food webs are very incomplete without parasites. Most notably, recognition of parasite links may have important consequences for ecosystem stability because they can increase connectance and nestedness.

Animals↗