Mitochondrial DNAs provide insight into trypanosome phylogeny and molecular evolution

Abstract Background: Trypanosomes are single-celled eukaryotic parasites characterised by the unique biology of their mitochondrial DNA (mtDNA). African livestock trypanosomes impose a major burden on agriculture across sub-Saharan Africa, but are poorly understood compared to those that cause sleeping sickness and Chagas disease in humans. Here we explore the potential of trypanosome mtDNA to study the evolutionary history of trypanosomes and the molecular evolution of their mtDNAs.Results: We used long-read sequencing to completely assemble mtDNAs from four previously uncharacterized African trypanosomes, and leveraged these assemblies to scaffold and assemble a further 103 trypanosome mtDNAs from published short-read data. While synteny was largely conserved, there were repeated, independent losses of Complex I genes. Comparison of edited and non-edited genes revealed the impact of RNA editing on nucleotide composition, with non-edited genes approaching the limits of GC loss. African tsetse-transmitted trypanosomes showed high levels of RNA editing compared to other trypanosomes. Whole mtDNA coding regions were used to construct time-resolved phylogenetic trees, revealing deep divergence events among isolates of the pathogens Trypanosoma brucei and T. congolense .Conclusions: Our mtDNA data represents a new resource for experimental and evolutionary analyses of trypanosome phylogeny, molecular evolution and function. Molecular clock analyses yielded a timescale for trypanosome evolution congruent with major biogeographical events in Africa and revealed the recent emergence of Trypanosoma brucei gambiense and T. equiperdum , major human and animal pathogens.

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Mitochondrial DNAs provide insight into trypanosome phylogeny and molecular evolution

10.21203/rs.3.rs-27858/v2 ◽

2020 ◽

Author(s):

Christopher Kay ◽

Tom A Williams ◽

Wendy Gibson

Keyword(s):

Mitochondrial Dna ◽

Molecular Evolution ◽

Trypanosoma Brucei ◽

Rna Editing ◽

Sub Saharan Africa ◽

Coding Regions ◽

Gene Coding ◽

Animal Pathogens ◽

Recent Emergence ◽

The Impact

Abstract Background: Trypanosomes are single-celled eukaryotic parasites characterised by the unique biology of their mitochondrial DNA. African livestock trypanosomes impose a major burden on agriculture across sub-Saharan Africa, but are poorly understood compared to those that cause sleeping sickness and Chagas disease in humans. Here we explore the potential of the maxicircle, a component of trypanosome mitochondrial DNA to study the evolutionary history of trypanosomes.Results: We used long-read sequencing to completely assemble maxicircle mitochondrial DNA from four previously uncharacterized African trypanosomes, and leveraged these assemblies to scaffold and assemble a further 103 trypanosome maxicircle gene coding regions from published short-read data. While synteny was largely conserved, there were repeated, independent losses of Complex I genes. Comparison of pre-edited and non-edited genes revealed the impact of RNA editing on nucleotide composition, with non-edited genes approaching the limits of GC loss. African tsetse-transmitted trypanosomes showed high levels of RNA editing compared to other trypanosomes. The gene coding regions of maxicircle mitochondrial DNAswere used to construct time-resolved phylogenetic trees, revealing deep divergence events among isolates of the pathogens Trypanosoma brucei and T. congolense. Conclusions: Our data represents a new resource for experimental and evolutionary analyses of trypanosome phylogeny, molecular evolution and function. Molecular clock analyses yielded a timescale for trypanosome evolution congruent with major biogeographical events in Africa and revealed the recent emergence of Trypanosoma brucei gambiense and T. equiperdum, major human and animal pathogens.

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Mitochondrial DNAs provide insight into trypanosome phylogeny and molecular evolution

BMC Evolutionary Biology ◽

10.1186/s12862-020-01701-9 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

C. Kay ◽

T. A. Williams ◽

W. Gibson

Keyword(s):

Mitochondrial Dna ◽

Molecular Evolution ◽

Trypanosoma Brucei ◽

Rna Editing ◽

Sub Saharan Africa ◽

Coding Regions ◽

Gene Coding ◽

Animal Pathogens ◽

Mitochondrial Dnas ◽

The Impact

Abstract Background Trypanosomes are single-celled eukaryotic parasites characterised by the unique biology of their mitochondrial DNA. African livestock trypanosomes impose a major burden on agriculture across sub-Saharan Africa, but are poorly understood compared to those that cause sleeping sickness and Chagas disease in humans. Here we explore the potential of the maxicircle, a component of trypanosome mitochondrial DNA to study the evolutionary history of trypanosomes. Results We used long-read sequencing to completely assemble maxicircle mitochondrial DNA from four previously uncharacterized African trypanosomes, and leveraged these assemblies to scaffold and assemble a further 103 trypanosome maxicircle gene coding regions from published short-read data. While synteny was largely conserved, there were repeated, independent losses of Complex I genes. Comparison of pre-edited and non-edited genes revealed the impact of RNA editing on nucleotide composition, with non-edited genes approaching the limits of GC loss. African tsetse-transmitted trypanosomes showed high levels of RNA editing compared to other trypanosomes. The gene coding regions of maxicircle mitochondrial DNAs were used to construct time-resolved phylogenetic trees, revealing deep divergence events among isolates of the pathogens Trypanosoma brucei and T. congolense. Conclusions Our data represents a new resource for experimental and evolutionary analyses of trypanosome phylogeny, molecular evolution and function. Molecular clock analyses yielded a timescale for trypanosome evolution congruent with major biogeographical events in Africa and revealed the recent emergence of Trypanosoma brucei gambiense and T. equiperdum, major human and animal pathogens.

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Gene Co-Expression Network Analysis of Trypanosoma brucei in Tsetse Fly Vector

10.21203/rs.3.rs-78868/v1 ◽

2020 ◽

Author(s):

Kennedy W. Mwangi ◽

Rosaline W. Macharia ◽

Joel L. Bargul

Keyword(s):

Trypanosoma Brucei ◽

Molecular Mechanisms ◽

Rna Binding ◽

Protein Biosynthesis ◽

Regulatory Elements ◽

Tsetse Fly ◽

Sub Saharan Africa ◽

Mammalian Host ◽

African Trypanosomes ◽

Gene Modules

Abstract BackgroundTrypanosoma brucei species are motile protozoan parasites that are cyclically transmitted by tsetse fly (genus Glossina) causing human sleeping sickness and nagana in livestock in sub-Saharan Africa. African trypanosomes display digenetic life cycle stages in the tsetse fly vector and in their mammalian host. Experimental work on insect-stage trypanosomes is challenging due to the difficulty in setting up successful in vitro cultures. Therefore, there is limited knowledge on the trypanosome biology during its development in the tsetse fly. Consequently, this limits the development of new strategies for blocking parasite transmission in the tsetse fly. MethodsIn this study, RNA-Seq data of insect-stage trypanosomes were used to construct a T. brucei gene co-expression network using weighted gene co-expression analysis (WGCNA) method. The study identified significant enriched modules for genes that play key roles during the parasite’s development in tsetse fly. Further, potential 3’ untranslated region (UTR) regulatory elements for genes that clustered in the same module were identified using Finding Informative Regulatory Elements (FIRE) tool.ResultsA fraction of gene modules (12 out of 27 modules) in the constructed network were found to be enriched in functional roles associated with cell division, protein biosynthesis, mitochondrion, and cell surface. Additionally, 12 hub genes encoding proteins such as RNA-binding protein 6 (RBP6), Arginine kinase 1 (AK1), brucei alanine rich protein (BARP), among others, were identified for the 12 significantly enriched gene modules. In addition, the potential regulatory elements located in the 3’ untranslated regions of genes within the same module were predicted. ConclusionsThe constructed gene co-expression network provides a useful resource for network-based data mining to identify candidate genes for functional studies. This will enhance understanding of the molecular mechanisms that underlie important biological processes during parasite’s development in tsetse fly. Ultimately, these findings will be key in the identification of potential molecular targets for disease control.

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Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation

mBio ◽

10.1128/mbio.00875-19 ◽

2019 ◽

Vol 10 (4) ◽

Cited By ~ 2

Author(s):

Balázs Szöőr ◽

Dorina V. Simon ◽

Federico Rojas ◽

Julie Young ◽

Derrick R. Robinson ◽

...

Keyword(s):

Life Cycle ◽

Trypanosoma Brucei ◽

Tyrosine Phosphatase ◽

Tsetse Fly ◽

Sub Saharan Africa ◽

Metabolic Adaptation ◽

Tsetse Flies ◽

Content Type ◽

African Trypanosomes ◽

Sub Saharan

ABSTRACT Glycosomes are peroxisome-related organelles that compartmentalize the glycolytic enzymes in kinetoplastid parasites. These organelles are developmentally regulated in their number and composition, allowing metabolic adaptation to the parasite’s needs in the blood of mammalian hosts or within their arthropod vector. A protein phosphatase cascade regulates differentiation between parasite developmental forms, comprising a tyrosine phosphatase, Trypanosoma brucei PTP1 (TbPTP1), which dephosphorylates and inhibits a serine threonine phosphatase, TbPIP39, which promotes differentiation. When TbPTP1 is inactivated, TbPIP39 is activated and during differentiation becomes located in glycosomes. Here we have tracked TbPIP39 recruitment to glycosomes during differentiation from bloodstream “stumpy” forms to procyclic forms. Detailed microscopy and live-cell imaging during the synchronous transition between life cycle stages revealed that in stumpy forms, TbPIP39 is located at a periflagellar pocket site closely associated with TbVAP, which defines the flagellar pocket endoplasmic reticulum. TbPTP1 is also located at the same site in stumpy forms, as is REG9.1, a regulator of stumpy-enriched mRNAs. This site provides a molecular node for the interaction between TbPTP1 and TbPIP39. Within 30 min of the initiation of differentiation, TbPIP39 relocates to glycosomes, whereas TbPTP1 disperses to the cytosol. Overall, the study identifies a “stumpy regulatory nexus” (STuRN) that coordinates the molecular components of life cycle signaling and glycosomal development during transmission of Trypanosoma brucei. IMPORTANCE African trypanosomes are parasites of sub-Saharan Africa responsible for both human and animal disease. The parasites are transmitted by tsetse flies, and completion of their life cycle involves progression through several development steps. The initiation of differentiation between blood and tsetse fly forms is signaled by a phosphatase cascade, ultimately trafficked into peroxisome-related organelles called glycosomes that are unique to this group of organisms. Glycosomes undergo substantial remodeling of their composition and function during the differentiation step, but how this is regulated is not understood. Here we identify a cytological site where the signaling molecules controlling differentiation converge before the dispersal of one of them into glycosomes. In combination, the study provides the first insight into the spatial coordination of signaling pathway components in trypanosomes as they undergo cell-type differentiation.

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Mitochondrial Dual-coding Genes in Trypanosoma brucei

10.1101/187732 ◽

2017 ◽

Author(s):

Laura E. Kirby ◽

Donna Koslowsky

Keyword(s):

Trypanosoma Brucei ◽

Rna Editing ◽

Genetic Drift ◽

Mitochondrial Genes ◽

Open Reading Frame ◽

Dual Coding ◽

Mutational Bias ◽

Reading Frame ◽

African Trypanosomes ◽

Reading Frames

AbstractTrypanosoma brucei is transmitted between mammalian hosts by the tsetse fly. In the mammal, they are exclusively extracellular, continuously replicating within the bloodstream. During this stage, the mitochondrion lacks a functional electron transport chain (ETC). Successful transition to the fly, requires activation of the ETC and ATP synthesis via oxidative phosphorylation. This life cycle leads to a major problem: in the bloodstream, the mitochondrial genes are not under selection and are subject to genetic drift that endangers their integrity. Exacerbating this, T. brucei undergoes repeated population bottlenecks as they evade the host immune system that would create additional forces of genetic drift. These parasites possess several unique genetic features, including RNA editing of mitochondrial transcripts. RNA editing creates open reading frames by the guided insertion and deletion of U-residues within the mRNA. A major question in the field has been why this metabolically expensive system of RNA editing would evolve and persist. Here, we show that many of the edited mRNAs can alter the choice of start codon and the open reading frame by alternative editing of the 5’ end. Analyses of mutational bias indicate that six of the mitochondrial genes may be dual-coding and that RNA editing allows access to both reading frames. We hypothesize that dual-coding genes can protect genetic information by essentially hiding a non-selected gene within one that remains under selection. Thus, the complex RNA editing system found in the mitochondria of trypanosomes provides a unique molecular strategy to combat genetic drift in non-selective conditions.Author SummaryIn African trypanosomes, many of the mitochondrial mRNAs require extensive RNA editing before they can be translated. During this process, each edited transcript can undergo hundreds of cleavage/ligation events as U-residues are inserted or deleted to generate a translatable open reading frame. A major paradox has been why this incredibly metabolically expensive process would evolve and persist. In this work, we show that many of the mitochondrial genes in trypanosomes are dual-coding, utilizing different reading frames to potentially produce two very different proteins. Access to both reading frames is made possible by alternative editing of the 5’ end of the transcript. We hypothesize that dual-coding genes may work to protect the mitochondrial genes from mutations during growth in the mammalian host, when many of the mitochondrial genes are not being used. Thus, the complex RNA editing system may be maintained because it provides a unique molecular strategy to combat genetic drift.

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Gene co-expression network analysis of Trypanosoma brucei in tsetse fly vector

Parasites & Vectors ◽

10.1186/s13071-021-04597-6 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Kennedy W. Mwangi ◽

Rosaline W. Macharia ◽

Joel L. Bargul

Keyword(s):

Trypanosoma Brucei ◽

Molecular Mechanisms ◽

Rna Binding ◽

Protein Biosynthesis ◽

Regulatory Elements ◽

Tsetse Fly ◽

Sub Saharan Africa ◽

Mammalian Host ◽

African Trypanosomes ◽

Gene Modules

Abstract Background Trypanosoma brucei species are motile protozoan parasites that are cyclically transmitted by tsetse fly (genus Glossina) causing human sleeping sickness and nagana in livestock in sub-Saharan Africa. African trypanosomes display digenetic life cycle stages in the tsetse fly vector and in their mammalian host. Experimental work on insect-stage trypanosomes is challenging because of the difficulty in setting up successful in vitro cultures. Therefore, there is limited knowledge on the trypanosome biology during its development in the tsetse fly. Consequently, this limits the development of new strategies for blocking parasite transmission in the tsetse fly. Methods In this study, RNA-Seq data of insect-stage trypanosomes were used to construct a T. brucei gene co-expression network using the weighted gene co-expression analysis (WGCNA) method. The study identified significant enriched modules for genes that play key roles during the parasite’s development in tsetse fly. Furthermore, potential 3′ untranslated region (UTR) regulatory elements for genes that clustered in the same module were identified using the Finding Informative Regulatory Elements (FIRE) tool. Results A fraction of gene modules (12 out of 27 modules) in the constructed network were found to be enriched in functional roles associated with the cell division, protein biosynthesis, mitochondrion, and cell surface. Additionally, 12 hub genes encoding proteins such as RNA-binding protein 6 (RBP6), arginine kinase 1 (AK1), brucei alanine-rich protein (BARP), among others, were identified for the 12 significantly enriched gene modules. In addition, the potential regulatory elements located in the 3′ untranslated regions of genes within the same module were predicted. Conclusions The constructed gene co-expression network provides a useful resource for network-based data mining to identify candidate genes for functional studies. This will enhance understanding of the molecular mechanisms that underlie important biological processes during parasite’s development in tsetse fly. Ultimately, these findings will be key in the identification of potential molecular targets for disease control.

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Conflicts in Biafra, Katanga and Cabinda as a result of the geopolitical legacy of colonialism

OOO Zhurnal Voprosy Istorii ◽

10.31166/voprosyistorii202010statyi60 ◽

2020 ◽

Vol 2020 (10-3) ◽

pp. 238-246

Author(s):

Olga Dzhenchakova

Keyword(s):

Democratic Republic ◽

Economic Factor ◽

Colonial Period ◽

Sub Saharan Africa ◽

Negative Consequences ◽

Post Colonial ◽

Republic Of The Congo ◽

Sub Saharan ◽

The Republic ◽

The Impact

The article considers the impact of the colonial past of some countries in sub-Saharan Africa and its effect on their development during the post-colonial period. The negative consequences of the geopolitical legacy of colonialism are shown on the example of three countries: Nigeria, the Democratic Republic of the Congo and the Republic of Angola, expressed in the emergence of conflicts in these countries based on ethno-cultural, religious and socio-economic contradictions. At the same time, the focus is made on the economic factor and the consequences of the consumer policy of the former metropolises pursuing their mercantile interests were mixed.

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