scholarly journals Conserved associations between G-quadruplex-forming DNA motifs and virulence gene families in malaria parasites

2020 ◽  
Author(s):  
Hunter L. Gage ◽  
Catherine J. Merrick
Keyword(s):  
Strong Association ◽  
Plasmodium Species ◽  
Virulence Gene ◽  
Gene Families ◽  
Prediction Algorithm ◽  
Chronic Infections ◽  
Malaria Parasites ◽  
Dna Motifs ◽  
Var Genes ◽  
G Quadruplex

Abstract Background : The Plasmodium genus of malaria parasites encodes several families of antigen-encoding genes. These genes tend to be hyper-variable, highly recombinogenic and variantly expressed. The best-characterized family is the var genes, exclusively found in the Laveranian subgenus of malaria parasites infecting humans and great apes. Var genes encode major virulence factors involved in immune evasion and the maintenance of chronic infections. In the human parasite P. falciparum , var gene recombination and diversification appear to be promoted by G-quadruplex (G4) DNA motifs, which are strongly associated with var genes in P. falciparum . Here, we investigated how this association might have evolved across Plasmodium species – both Laverania and also more distantly related species which lack var s but encode other, more ancient variant gene families. Results : The association between var genes and G4-forming motifs was conserved across Laverania, spanning ~1 million years of evolutionary time, with suggestive evidence for evolution of the association occurring within this subgenus. In rodent malaria species, G4-forming motifs were somewhat associated with pir genes, but this was not conserved in the Laverania, nor did we find a strong association of these motifs with any gene family in a second outgroup of avian malaria parasites. Secondly, we compared two different G4 prediction algorithms in their performance on extremely A/T-rich Plasmodium genomes, and also compared these predictions with experimental data from G4-seq, a DNA sequencing method for identifying G4-forming motifs. We found a surprising lack of concordance between the two algorithms and also between the algorithms and G4-seq data. Conclusions: G4-forming motifs are uniquely strongly associated with Plasmodium var genes, suggesting a particular role for G4s in recombination and diversification of these genes. Secondly, in the A/T-rich genomes of Plasmodium species, the choice of prediction algorithm may be particularly influential when studying G4s in these important protozoan pathogens.

scholarly journals Conserved associations between G-quadruplex-forming DNA motifs and virulence gene families in malaria parasites

2019 ◽  
Author(s):  
Hunter L. Gage ◽  
Catherine J. Merrick
Keyword(s):  
Strong Association ◽  
Plasmodium Species ◽  
Virulence Gene ◽  
Gene Families ◽  
Prediction Algorithm ◽  
Chronic Infections ◽  
Malaria Parasites ◽  
Dna Motifs ◽  
Var Genes ◽  
G Quadruplex

Abstract Background: The Plasmodium genus of malaria parasites encodes several families of antigen-encoding genes. These genes tend to be hyper-variable, highly recombinogenic and variantly expressed. The best-characterized family is the var genes, exclusively found in the Laveranian subgenus of malaria parasites infecting humans and great apes. Var genes encode major virulence factors involved in immune evasion and the maintenance of chronic infections. In the human parasite P. falciparum, var gene recombination and diversification appear to be promoted by G-quadruplex (G4) DNA motifs, which are strongly associated with var genes in P. falciparum. Here, we investigated how this association might have evolved across Plasmodium species – both Laverania and also more distantly related species which lack vars but encode other, more ancient variant gene families. Results: The association between var genes and G4-forming motifs was conserved across Laverania, spanning ~1 million years of evolutionary time, with suggestive evidence for evolution of the association occurring within this subgenus. In rodent malaria species, G4-forming motifs were somewhat associated with pir genes, but this was not conserved in the Laverania, nor did we find a strong association of these motifs with any gene family in a second outgroup of avian malaria parasites. Secondly, we compared two different G4 prediction algorithms in their performance on extremely A/T-rich Plasmodium genomes, and also compared these predictions with experimental data from G4-seq, a DNA sequencing method for identifying G4-forming motifs. We found a surprising lack of concordance between the two algorithms and also between the algorithms and G4-seq data. Conclusions: G4-forming motifs are uniquely strongly associated with Plasmodium var genes, suggesting a particular role for G4s in recombination and diversification of these genes. Secondly, in the A/T-rich genomes of Plasmodium species, the choice of prediction algorithm may be particularly influential when studying G4s in these important protozoan pathogens.

scholarly journals Conserved associations between G-quadruplex-forming DNA motifs and virulence gene families in malaria parasites

2020 ◽  
Author(s):  
Hunter L. Gage ◽  
Catherine J. Merrick
Keyword(s):  
Strong Association ◽  
Plasmodium Species ◽  
Virulence Gene ◽  
Gene Families ◽  
Prediction Algorithm ◽  
Chronic Infections ◽  
Malaria Parasites ◽  
Dna Motifs ◽  
Var Genes ◽  
G Quadruplex

Abstract Background: The Plasmodium genus of malaria parasites encodes several families of antigen-encoding genes. These genes tend to be hyper-variable, highly recombinogenic and variantly expressed. The best-characterized family is the var genes, exclusively found in the Laveranian subgenus of malaria parasites infecting humans and great apes. Var genes encode major virulence factors involved in immune evasion and the maintenance of chronic infections. In the human parasite P. falciparum, var gene recombination and diversification appear to be promoted by G-quadruplex (G4) DNA motifs, which are strongly associated with var genes in P. falciparum. Here, we investigated how this association might have evolved across Plasmodium species – both Laverania and also more distantly related species which lack vars but encode other, more ancient variant gene families. Results: The association between var genes and G4-forming motifs was conserved across Laverania, spanning ~1 million years of evolutionary time, with suggestive evidence for evolution of the association occurring within this subgenus. In rodent malaria species, G4-forming motifs were somewhat associated with pir genes, but this was not conserved in the Laverania, nor did we find a strong association of these motifs with any gene family in a second outgroup of avian malaria parasites. Secondly, we compared two different G4 prediction algorithms in their performance on extremely A/T-rich Plasmodium genomes, and also compared these predictions with experimental data from G4-seq, a DNA sequencing method for identifying G4-forming motifs. We found a surprising lack of concordance between the two algorithms and also between the algorithms and G4-seq data. Conclusions: G4-forming motifs are uniquely strongly associated with Plasmodium var genes, suggesting a particular role for G4s in recombination and diversification of these genes. Secondly, in the A/T-rich genomes of Plasmodium species, the choice of prediction algorithm may be particularly influential when studying G4s in these important protozoan pathogens.

scholarly journals Recombination events among virulence genes in malaria parasites are associated with G-quadruplex-forming DNA motifs

BMC Genomics ◽  
2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Adam Stanton ◽  
Lynne M. Harris ◽  
Gemma Graham ◽  
Catherine J. Merrick
Keyword(s):  
Virulence Genes ◽  
Malaria Parasites ◽  
Dna Motifs ◽  
G Quadruplex

scholarly journals Non-human primate and human malaria: past, present and future

2021 ◽  
Author(s):  
Spinello Antinori ◽  
Cecilia Bonazzetti ◽  
Andrea Giacomelli ◽  
Mario Corbellino ◽  
Massimo Galli ◽  
...  
Keyword(s):  
Plasmodium Knowlesi ◽  
Plasmodium Species ◽  
Molecular Techniques ◽  
Malaria Parasites ◽  
Human Malaria ◽  
Complex Interactions ◽  
Zoonotic Malaria ◽  
The Impact ◽  
Human Plasmodium ◽  
Human Primate

Abstract Background Studies of the malaria parasites infecting various non-human primates (NHPs) have increased our understanding of the origin, biology and pathogenesis of human Plasmodium parasites. This review considers the major discoveries concerning NHP malaria parasites, highlights their relationships with human malaria and considers the impact that this may have on attempts to eradicate the disease. Results The first description of NHP malaria parasites dates back to the early 20th century. Subsequently, experimental and fortuitous findings indicating that some NHP malaria parasites can be transmitted to humans have raised concerns about the possible impact of a zoonotic malaria reservoir on efforts to control human malaria. Advances in molecular techniques over the last 15 years have contributed greatly to our knowledge of the existence and geographical distribution of numerous Plasmodium species infecting NHPs, and extended our understanding of their close phylogenetic relationships with human malaria parasites. The clinical application of such techniques has also made it possible to document ongoing spillovers of NHP malaria parasites (Plasmodium knowlesi, P. cynomolgi, P. simium, P. brasilianum) in humans living in or near the forests of Asia and South America, thus confirming that zoonotic malaria can undermine efforts to eradicate human malaria. Conclusions Increasing molecular research supports the prophetic intuition of the pioneers of modern malariology who saw zoonotic malaria as a potential obstacle to the full success of malaria eradication programmes. It is, therefore, important to continue surveillance and research based on one-health approaches in order to improve our understanding of the complex interactions between NHPs, mosquito vectors and humans during a period of ongoing changes in the climate and the use of land, monitor the evolution of zoonotic malaria, identify the populations most at risk and implement appropriate preventive strategies.

scholarly journals Assessing Diversity, Plasmodium Infection and Blood Meal Sources in Mosquitoes (Diptera: Culicidae) from a Brazilian Zoological Park with Avian Malaria Transmission

Insects ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 215
Author(s):  
Lilian de Oliveira Guimarães ◽  
Roseli França Simões ◽  
Carolina Romeiro Fernandes Chagas ◽  
Regiane Maria Tironi de Menezes ◽  
Fabiana Santos Silva ◽  
...  
Keyword(s):  
Blood Meal ◽  
Avian Malaria ◽  
Mosquito Species ◽  
Plasmodium Species ◽  
Sao Paulo ◽  
São Paulo ◽  
Malaria Parasites ◽  
Ecological Relationships ◽  
Lack Of Information ◽  
Avian Malaria Parasites

Avian malaria parasites are widespread parasites transmitted by Culicidae insects belonging to different genera. Even though several studies have been conducted recently, there is still a lack of information about potential vectors of Plasmodium parasites, especially in Neotropical regions. Former studies with free-living and captive animals in São Paulo Zoo showed the presence of several Plasmodium and Haemoproteus species. In 2015, a pilot study was conducted at the zoo to collect mosquitoes in order to find out (i) which species of Culicidae are present in the study area, (ii) what are their blood meal sources, and (iii) to which Plasmodium species might they be potential vectors. Mosquitoes were morphologically and molecularly identified. Blood meal source and haemosporidian DNA were identified using molecular protocols. A total of 25 Culicidae species were identified, and 6 of them were positive for Plasmodium/Haemoproteus DNA. Ten mosquito species had their source of blood meal identified, which were mainly birds, including some species that were positive for haemosporidian parasites in the former study mentioned. This study allowed us to expand the list of potential vectors of avian malaria parasites and to improve our knowledge of the evolutionary and ecological relationships between the highly diverse communities of birds, parasites, and vectors present at São Paulo Zoo.

scholarly journals Genome sequence, transcriptome, and annotation of rodent malaria parasite Plasmodium yoelii nigeriensis N67

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Cui Zhang ◽  
Cihan Oguz ◽  
Sue Huse ◽  
Lu Xia ◽  
Jian Wu ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Malaria Parasite ◽  
Vaccine Development ◽  
De Novo ◽  
Gene Families ◽  
Plasmodium Yoelii ◽  
Control Measures ◽  
Effective Control ◽  
Malaria Parasites ◽  
Rodent Malaria

Abstract Background Rodent malaria parasites are important models for studying host-malaria parasite interactions such as host immune response, mechanisms of parasite evasion of host killing, and vaccine development. One of the rodent malaria parasites is Plasmodium yoelii, and multiple P. yoelii strains or subspecies that cause different disease phenotypes have been widely employed in various studies. The genomes and transcriptomes of several P. yoelii strains have been analyzed and annotated, including the lethal strains of P. y. yoelii YM (or 17XL) and non-lethal strains of P. y. yoelii 17XNL/17X. Genomic DNA sequences and cDNA reads from another subspecies P. y. nigeriensis N67 have been reported for studies of genetic polymorphisms and parasite response to drugs, but its genome has not been assembled and annotated. Results We performed genome sequencing of the N67 parasite using the PacBio long-read sequencing technology, de novo assembled its genome and transcriptome, and predicted 5383 genes with high overall annotation quality. Comparison of the annotated genome of the N67 parasite with those of YM and 17X parasites revealed a set of genes with N67-specific orthology, expansion of gene families, particularly the homologs of the Plasmodium chabaudi erythrocyte membrane antigen, large numbers of SNPs and indels, and proteins predicted to interact with host immune responses based on their functional domains. Conclusions The genomes of N67 and 17X parasites are highly diverse, having approximately one polymorphic site per 50 base pairs of DNA. The annotated N67 genome and transcriptome provide searchable databases for fast retrieval of genes and proteins, which will greatly facilitate our efforts in studying the parasite biology and gene function and in developing effective control measures against malaria.

scholarly journals OVERVIEW OF MALARIA PARASITE AND ITS PREVENTION IN INDIA

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Adil Raza ◽  
Megha Chaudhary ◽  
Sonika Devi
Keyword(s):  
Red Blood Cells ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Malaria Parasite ◽  
Plasmodium Species ◽  
Peripheral Blood Smear ◽  
Infected Mosquito ◽  
Protozoan Parasites ◽  
Malaria Parasites ◽  
Genus Plasmodium

Background: Malaria is a systematic disease caused by a parasite called Plasmodium which is transmitted into the human blood via female Anopheles mosquito. Malaria in humans is caused by four species of protozoan parasites of the genus Plasmodium: P. falciparum, P. vivax, P. ovale, and P. malariae. The parasite enters the human body through a mosquito bite and travel to the very crucial organ, the liver, where they multiply and come back to the bloodstream and destroy red blood cells. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma, or death. Symptoms usually begin ten to fifteen days after being bitten by an infected mosquito. In those who have recently survived an infection, reinfection usually causes milder symptoms. Objectives: Isolation of different species of malaria parasites. The prevalence of malaria parasite in India. Methods: The procedure follows these steps: collection of peripheral blood, staining of smear with Leishman’s stain and examination of red blood cells for malaria parasites under the microscope. Results: We observed the plasmodium species in peripheral blood smear. Conclusion: Worldwide, the number of cases of malaria caused by Plasmodium falciparum, the most dangerous species of the parasite, is on the rise.

scholarly journals 5' flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites

2007 ◽  
Vol 0 (0) ◽  
pp. 071119190133003-??? ◽  
Author(s):  
Jose Juan Lopez-Rubio ◽  
Alisson M. Gontijo ◽  
Marta C. Nunes ◽  
Neha Issar ◽  
Rosaura Hernandez Rivas ◽  
...  
Keyword(s):  
Histone Modification ◽  
Malaria Parasites ◽  
Var Genes ◽  
Virulence Traits ◽  
Flanking Region ◽  
Histone Modification Patterns

scholarly journals RNA G-Quadruplex Structures Mediate Gene Regulation in Bacteria

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaolong Shao ◽  
Weitong Zhang ◽  
Mubarak Ishaq Umar ◽  
Hei Yuen Wong ◽  
Zijing Seng ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Cell Envelope ◽  
Bacterial Species ◽  
Virulence Gene ◽  
Content Type ◽  
Cellular Processes ◽  
Wide Range ◽  
G Quadruplex ◽  
Eukaryotic Organisms

ABSTRACT Guanine (G)-rich sequences in RNA can fold into diverse RNA G-quadruplex (rG4) structures to mediate various biological functions and cellular processes in eukaryotic organisms. However, the presence, locations, and functions of rG4s in prokaryotes are still elusive. We used QUMA-1, an rG4-specific fluorescent probe, to detect rG4 structures in a wide range of bacterial species both in vitro and in live cells and found rG4 to be an abundant RNA secondary structure across those species. Subsequently, to identify bacterial rG4 sites in the transcriptome, the model Escherichia coli strain and a major human pathogen, Pseudomonas aeruginosa, were subjected to recently developed high-throughput rG4 structure sequencing (rG4-seq). In total, 168 and 161 in vitro rG4 sites were found in E. coli and P. aeruginosa, respectively. Genes carrying these rG4 sites were found to be involved in virulence, gene regulation, cell envelope synthesis, and metabolism. More importantly, biophysical assays revealed the formation of a group of rG4 sites in mRNAs (such as hemL and bswR), and they were functionally validated in cells by genetic (point mutation and lux reporter assays) and phenotypic experiments, providing substantial evidence for the formation and function of rG4s in bacteria. Overall, our study uncovers important regulatory functions of rG4s in bacterial pathogenicity and metabolic pathways and strongly suggests that rG4s exist and can be detected in a wide range of bacterial species. IMPORTANCE G-quadruplex in RNA (rG4) mediates various biological functions and cellular processes in eukaryotic organisms. However, the presence, locations, and functions of rG4 are still elusive in prokaryotes. Here, we found that rG4 is an abundant RNA secondary structure across a wide range of bacterial species. Subsequently, the transcriptome-wide rG4 structure sequencing (rG4-seq) revealed that the model E. coli strain and a major human pathogen, P. aeruginosa, have 168 and 161 in vitro rG4 sites, respectively, involved in virulence, gene regulation, cell envelope, and metabolism. We further verified the regulatory functions of two rG4 sites in bacteria (hemL and bswR). Overall, this finding strongly suggests that rG4s play key regulatory roles in a wide range of bacterial species.

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