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

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Hunter L. Gage ◽  
Catherine J. Merrick
Keyword(s):  
Virulence Gene ◽  
Gene Families ◽  
Malaria Parasites ◽  
Dna Motifs ◽  
G Quadruplex

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 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

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 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 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.

scholarly journals Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Michelle C. Siao ◽  
Janus Borner ◽  
Susan L. Perkins ◽  
Kirk W. Deitsch ◽  
Laura A. Kirkman
Keyword(s):  
Gene Family ◽  
Family Members ◽  
Gene Families ◽  
Genome Integrity ◽  
Human Populations ◽  
Protozoan Parasites ◽  
Malaria Parasites ◽  
Content Type ◽  
Ectopic Recombination ◽  
Host Parasite

ABSTRACT The protozoan parasites that cause malaria infect a wide variety of vertebrate hosts, including birds, reptiles, and mammals, and the evolutionary pressures inherent to the host-parasite relationship have profoundly shaped the genomes of both host and parasite. Here, we report that these selective pressures have resulted in unexpected alterations to one of the most basic aspects of eukaryotic biology, the maintenance of genome integrity through DNA repair. Malaria parasites that infect humans continuously generate genetic diversity within their antigen-encoding gene families through frequent ectopic recombination between gene family members, a process that is a crucial feature of the persistence of malaria globally. The continuous generation of antigen diversity ensures that different parasite isolates are antigenically distinct, thus preventing extensive cross-reactive immunity and enabling parasites to maintain stable transmission within human populations. However, the molecular basis of the recombination between gene family members is not well understood. Through computational analyses of the antigen-encoding, multicopy gene families of different Plasmodium species, we report the unexpected observation that malaria parasites that infect rodents do not display the same degree of antigen diversity as observed in Plasmodium falciparum and appear to undergo significantly less ectopic recombination. Using comparative genomics, we also identify key molecular components of the diversification process, thus shedding new light on how malaria parasites balance the maintenance of genome integrity with the requirement for continuous genetic diversification. IMPORTANCE Malaria remains one of the most prevalent and deadly infectious diseases of the developing world, causing approximately 228 million clinical cases and nearly half a million deaths annually. The disease is caused by protozoan parasites of the genus Plasmodium, and of the five species capable of infecting humans, infections with P. falciparum are the most severe. In addition to the parasites that infect people, there are hundreds of additional species that infect birds, reptiles, and other mammals, each exquisitely evolved to meet the specific challenges inherent to survival within their respective hosts. By comparing the unique strategies that each species has evolved, key insights into host-parasite interactions can be gained, including discoveries regarding the pathogenesis of human disease. Here, we describe the surprising observation that closely related parasites with different hosts have evolved remarkably different methods for repairing their genomes. This observation has important implications for the ability of parasites to maintain chronic infections and for the development of host immunity.

scholarly journals Analysis of subtelomeric virulence gene families in Plasmodium falciparum by comparative transcriptional profiling

2012 ◽  
Vol 84 (2) ◽  
pp. 243-259 ◽  
Author(s):  
Kathrin Witmer ◽  
Christoph D. Schmid ◽  
Nicolas M. B. Brancucci ◽  
Yen‐Hoon Luah ◽  
Peter R. Preiser ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Transcriptional Profiling ◽  
Virulence Gene ◽  
Gene Families

scholarly journals Self-assembled Pt2L2 boxes strongly bind G-quadruplex DNA and influence gene expression in cancer cells

2017 ◽  
Vol 46 (2) ◽  
pp. 329-332 ◽  
Author(s):  
O. Domarco ◽  
D. Lötsch ◽  
J. Schreiber ◽  
C. Dinhof ◽  
S. Van Schoonhoven ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Cells ◽  
Quadruplex Dna ◽  
Dna Motifs ◽  
Size Dependent ◽  
G Quadruplex ◽  
Self Assembled ◽  
Influence Gene Expression

Pt(ii) boxes bind native and G-quadruplex DNA motifs in a size-dependent fashion and influence the expression of G-quadruplex forming genes.

scholarly journals What drives recombination hotspots to repeat DNA in humans?

2010 ◽  
Vol 365 (1544) ◽  
pp. 1213-1218 ◽  
Author(s):  
Gil McVean
Keyword(s):  
Active Element ◽  
Rapid Evolution ◽  
Gene Families ◽  
Double Strand Breaks ◽  
Segmental Duplications ◽  
Repeat Elements ◽  
Strand Breaks ◽  
Dna Motifs ◽  
Recombination Hotspots ◽  
Repeat Dna

Recombination between homologous, but non-allelic, stretches of DNA such as gene families, segmental duplications and repeat elements is an important source of mutation. In humans, recent studies have identified short DNA motifs that both determine the location of 40 per cent of meiotic cross-over hotspots and are significantly enriched at the breakpoints of recurrent non-allelic homologous recombination (NAHR) syndromes. Unexpectedly, the most highly penetrant form of the motif occurs on the background of an inactive repeat element family (THE1 elements) and the motif also has strong recombinogenic activity on currently active element families including Alu and LINE2 elements. Analysis of genetic variation among members of these repeat families indicates an important role for NAHR in their evolution. Given the potential for double-strand breaks within repeat DNA to cause pathological rearrangement, the association between repeats and hotspots is surprising. Here we consider possible explanations for why selection acting against NAHR has not eliminated hotspots from repeat DNA including mechanistic constraints, possible benefits to repeat DNA from recruiting hotspots and rapid evolution of the recombination machinery. I suggest that rapid evolution of hotspot motifs may, surprisingly, tend to favour sequences present in repeat DNA and outline the data required to differentiate between hypotheses.

Sign in / Sign up

Export Citation Format

Share Document