scholarly journals Gregarine single-cell transcriptomics reveals differential mitochondrial remodeling and adaptation in apicomplexans

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Eric D. Salomaki ◽  
Kristina X. Terpis ◽  
Sonja Rueckert ◽  
Michael Kotyk ◽  
Zuzana Kotyková Varadínová ◽  
...  
Keyword(s):  
Single Cell ◽  
Evolutionary Relationship ◽  
Mitochondrial Metabolism ◽  
Human Pathogens ◽  
Cryptosporidium Hominis ◽  
Microbial Eukaryotes ◽  
Transport Chain ◽  
Phylogenomic Analyses ◽  
Mitochondrial Remodeling ◽  
Genome Scale

Abstract Background Apicomplexa is a diverse phylum comprising unicellular endobiotic animal parasites and contains some of the most well-studied microbial eukaryotes including the devastating human pathogens Plasmodium falciparum and Cryptosporidium hominis. In contrast, data on the invertebrate-infecting gregarines remains sparse and their evolutionary relationship to other apicomplexans remains obscure. Most apicomplexans retain a highly modified plastid, while their mitochondria remain metabolically conserved. Cryptosporidium spp. inhabit an anaerobic host-gut environment and represent the known exception, having completely lost their plastid while retaining an extremely reduced mitochondrion that has lost its genome. Recent advances in single-cell sequencing have enabled the first broad genome-scale explorations of gregarines, providing evidence of differential plastid retention throughout the group. However, little is known about the retention and metabolic capacity of gregarine mitochondria. Results Here, we sequenced transcriptomes from five species of gregarines isolated from cockroaches. We combined these data with those from other apicomplexans, performed detailed phylogenomic analyses, and characterized their mitochondrial metabolism. Our results support the placement of Cryptosporidium as the earliest diverging lineage of apicomplexans, which impacts our interpretation of evolutionary events within the phylum. By mapping in silico predictions of core mitochondrial pathways onto our phylogeny, we identified convergently reduced mitochondria. These data show that the electron transport chain has been independently lost three times across the phylum, twice within gregarines. Conclusions Apicomplexan lineages show variable functional restructuring of mitochondrial metabolism that appears to have been driven by adaptations to parasitism and anaerobiosis. Our findings indicate that apicomplexans are rife with convergent adaptations, with shared features including morphology, energy metabolism, and intracellularity.

scholarly journals Using single-cell transcriptomics to understand functional states and interactions in microbial eukaryotes

2019 ◽  
Vol 374 (1786) ◽  
pp. 20190098 ◽  
Author(s):  
Chuan Ku ◽  
Arnau Sebé-Pedrós
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Interspecific Interactions ◽  
Single Cells ◽  
Life Cycles ◽  
Modern Biology ◽  
Microbial Eukaryotes ◽  
Eukaryotic Microorganisms

Understanding the diversity and evolution of eukaryotic microorganisms remains one of the major challenges of modern biology. In recent years, we have advanced in the discovery and phylogenetic placement of new eukaryotic species and lineages, which in turn completely transformed our view on the eukaryotic tree of life. But we remain ignorant of the life cycles, physiology and cellular states of most of these microbial eukaryotes, as well as of their interactions with other organisms. Here, we discuss how high-throughput genome-wide gene expression analysis of eukaryotic single cells can shed light on protist biology. First, we review different single-cell transcriptomics methodologies with particular focus on microbial eukaryote applications. Then, we discuss single-cell gene expression analysis of protists in culture and what can be learnt from these approaches. Finally, we envision the application of single-cell transcriptomics to protist communities to interrogate not only community components, but also the gene expression signatures of distinct cellular and physiological states, as well as the transcriptional dynamics of interspecific interactions. Overall, we argue that single-cell transcriptomics can significantly contribute to our understanding of the biology of microbial eukaryotes. This article is part of a discussion meeting issue ‘Single cell ecology’.

scholarly journals Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy

2020 ◽  
Vol 21 (21) ◽  
pp. 7941 ◽  
Author(s):  
Lanfeng Dong ◽  
Vinod Gopalan ◽  
Olivia Holland ◽  
Jiri Neuzil
Keyword(s):  
Cancer Progression ◽  
Tricarboxylic Acid Cycle ◽  
Cancer Therapeutics ◽  
Mitochondrial Metabolism ◽  
Signalling Pathways ◽  
Transport Chain ◽  
Ros Homeostasis ◽  
Mitochondrial Functions ◽  
Anti Cancer ◽  
Selective Targeting

Mitochondria are essential cellular organelles, controlling multiple signalling pathways critical for cell survival and cell death. Increasing evidence suggests that mitochondrial metabolism and functions are indispensable in tumorigenesis and cancer progression, rendering mitochondria and mitochondrial functions as plausible targets for anti-cancer therapeutics. In this review, we summarised the major strategies of selective targeting of mitochondria and their functions to combat cancer, including targeting mitochondrial metabolism, the electron transport chain and tricarboxylic acid cycle, mitochondrial redox signalling pathways, and ROS homeostasis. We highlight that delivering anti-cancer drugs into mitochondria exhibits enormous potential for future cancer therapeutic strategies, with a great advantage of potentially overcoming drug resistance. Mitocans, exemplified by mitochondrially targeted vitamin E succinate and tamoxifen (MitoTam), selectively target cancer cell mitochondria and efficiently kill multiple types of cancer cells by disrupting mitochondrial function, with MitoTam currently undergoing a clinical trial.

A Genome-Scale Metabolic Model of Cryptosporidium hominis

2010 ◽  
Vol 7 (5) ◽  
pp. 1026-1039 ◽  
Author(s):  
Niti Vanee ◽  
Seth B. Roberts ◽  
Stephen S. Fong ◽  
Patricio Manque ◽  
Gregory A. Buck
Keyword(s):  
Metabolic Model ◽  
Cryptosporidium Hominis ◽  
A Genome ◽  
Genome Scale

Plant genome-scale reconstruction: from single cell to multi-tissue modelling and omics analyses

2018 ◽  
Vol 49 ◽  
pp. 42-48 ◽  
Author(s):  
Cristiana Gomes de Oliveira Dal’Molin ◽  
Lars Keld Nielsen
Keyword(s):  
Single Cell ◽  
Plant Genome ◽  
Genome Scale ◽  
Tissue Modelling

scholarly journals Corallimorpharians are not “naked corals”: insights into relationships between Scleractinia and Corallimorpharia from phylogenomic analyses

2016 ◽  
Author(s):  
Mei Fang Lin ◽  
Wen Hwa Chou ◽  
Marcelo V Kitahara ◽  
Chao Lun Allen Chen ◽  
David John Miller ◽  
...  
Keyword(s):  
Evolutionary Relationship ◽  
Single Copy ◽  
Scleractinian Corals ◽  
Amino Acid Sequences ◽  
Compositional Bias ◽  
Nuclear Markers ◽  
Protein Coding ◽  
Mitochondrial Sequences ◽  
Phylogenomic Analyses ◽  
Close Relatives

Calcification is one of the most distinctive traits of scleractinian corals. Their hard skeletons form the substratum of reef ecosystems and confer on corals their remarkable diversity of shapes. Corallimorpharians are non-calcifying, close relatives of scleractinian corals, and the evolutionary relationship between these two groups is key to understanding the evolution of calcification in the coral lineage. One pivotal question is whether scleractinians are a monophyletic group, paraphyly being an alternative possibility if corallimorpharians are corals that have lost their ability to calcify, as is implied by the “naked-coral” hypothesis. Despite major efforts, relationships between scleractinians and corallimorpharians remain equivocal and controversial. Although the complete mitochondrial genomes of a range of scleractinians and corallimorpharians have been obtained, heterogeneity in composition and evolutionary rates means that mitochondrial sequences are insufficient to understand the relationship between these two groups. To overcome these limitations, transcriptome data were generated for three representative corallimorpharians. These were used in combination with sequences available for a representative range of scleractinians to identify 291 orthologous single copy protein-coding nuclear markers. Unlike the mitochondrial sequences, these nuclear markers do not display any distinct compositional bias in their nucleotide or amino-acid sequences. A range of phylogenomic approaches congruently reveal a topology consistent with scleractinian monophyly and corallimorpharians as the sister clade of scleractinians.

scholarly journals A quantitative framework for evaluating single-cell data structure preservation by dimensionality reduction techniques

2019 ◽  
Author(s):  
Cody N. Heiser ◽  
Ken S. Lau
Keyword(s):  
Data Structure ◽  
Dimensionality Reduction ◽  
Single Cell ◽  
Structure Preservation ◽  
Reduction Techniques ◽  
Reduction Methods ◽  
Biological Interpretation ◽  
Low Dimensional ◽  
Genome Scale ◽  
Global And Local

SummaryHigh-dimensional data, such as those generated using single-cell RNA sequencing, present challenges in interpretation and visualization. Numerical and computational methods for dimensionality reduction allow for low-dimensional representation of genome-scale expression data for downstream clustering, trajectory reconstruction, and biological interpretation. However, a comprehensive and quantitative evaluation of the performance of these techniques has not been established. We present an unbiased framework that defines metrics of global and local structure preservation in dimensionality reduction transformations. Using discrete and continuous scRNA-seq datasets, we find that input cell distribution and method parameters are largely determinant of global, local, and organizational data structure preservation by eleven published dimensionality reduction methods. Code available atgithub.com/KenLauLab/DR-structure-preservationallows for rapid evaluation of further datasets and methods.

scholarly journals Did viruses evolve as a distinct supergroup from common ancestors of cells?

2016 ◽  
Author(s):  
Ajith Harish ◽  
Aare Abroi ◽  
Julian Gough ◽  
Charles Kurland
Keyword(s):  
Common Ancestor ◽  
Phylogenetic Analyses ◽  
Marker Gene ◽  
Host Cells ◽  
Data Driven ◽  
Evolutionary Origins ◽  
Phylogenetic Methods ◽  
Universal Common Ancestor ◽  
Phylogenomic Analyses ◽  
Genome Scale

AbstractThe evolutionary origins of viruses according to marker gene phylogenies, as well as their relationships to the ancestors of host cells remains unclear. In a recent article Nasir and Caetano-Anollés reported that their genome-scale phylogenetic analyses identify an ancient origin of the “viral supergroup” (Nasir et al (2015) A phylogenomic data-driven exploration of viral origins and evolution. Science Advances, 1(8):e1500527). It suggests that viruses and host cells evolved independently from a universal common ancestor. Examination of their data and phylogenetic methods indicates that systematic errors likely affected the results. Reanalysis of the data with additional tests shows that small-genome attraction artifacts distort their phylogenomic analyses. These new results indicate that their suggestion of a distinct ancestry of the viral supergroup is not well supported by the evidence.

scholarly journals Multiple independent origins of apicomplexan-like parasites

2019 ◽  
Author(s):  
Varsha Mathur ◽  
Martin Kolisko ◽  
Elisabeth Hehenberger ◽  
Nicholas AT Irwin ◽  
Brian S. Leander ◽  
...  
Keyword(s):  
Single Cell ◽  
Causative Agent ◽  
Diverse Group ◽  
Evolutionary Transition ◽  
Single Cell Genomics ◽  
Parasitic Lifestyle ◽  
Phylogenomic Analyses

AbstractApicomplexans are a diverse group of globally important parasites, that include pathogens like Plasmodium, the causative agent of malaria. Despite their current obligate parasitic nature, apicomplexans evolved from photosynthetic algae and retain a remnant plastid (chloroplast). Such a complex evolutionary transition was unexpected, but here we show that it occurred at least three times independently. Using single-cell genomics and transcriptomics from diverse uncultivated parasites, we find that two genera previously classified within the Apicomplexa, Piridium and Platyproteum, form separately branching lineages in phylogenomic analyses. Both retain cryptic plastids with genomic and metabolic features convergent with apicomplexans. These findings suggest a predilection in this lineage for both the loss of photosynthesis and the transition to a morphologically similar parasitic lifestyle, resulting in multiple lineages of highly convergent animal parasites.

scholarly journals Genome-scale oscillations in DNA methylation during exit from pluripotency

2018 ◽  
Author(s):  
Steffen Rulands ◽  
Heather J Lee ◽  
Stephen J Clark ◽  
Christof Angermueller ◽  
Sébastien A Smallwood ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Single Cell ◽  
Epigenetic Mark ◽  
List Type ◽  
Dna Hypomethylation ◽  
Cell Fate Decisions ◽  
Oscillatory Dynamics ◽  
Genome Scale

SummaryPluripotency is accompanied by the erasure of parental epigenetic memory with naïve pluripotent cells exhibiting global DNA hypomethylation both in vitro and in vivo. Exit from pluripotency and priming for differentiation into somatic lineages is associated with genome-wide de novo DNA methylation. We show that during this phase, coexpression of enzymes required for DNA methylation turnover, DNMT3s and TETs, promotes cell-to-cell variability in this epigenetic mark. Using a combination of single-cell sequencing and quantitative biophysical modelling, we show that this variability is associated with coherent, genome-scale, oscillations in DNA methylation with an amplitude dependent on CpG density. Analysis of parallel single-cell transcriptional and epigenetic profiling provides evidence for oscillatory dynamics both in vitro and in vivo. These observations provide fresh insights into the emergence of epigenetic heterogeneity during early embryo development, indicating that dynamic changes in DNA methylation might influence early cell fate decisions.HighlightsCo-expression of DNMT3s and TETs drive genome-scale oscillations of DNA methylationOscillation amplitude is greatest at a CpG density characteristic of enhancersCell synchronisation reveals oscillation period and link with primary transcriptsMultiomic single-cell profiling provides evidence for oscillatory dynamics in vivo

scholarly journals Why do phylogenomic analyses of early animal evolution continue to disagree? Sites in different structural environments yield different answers

2018 ◽  
Author(s):  
Akanksha Pandey ◽  
Edward L. Braun
Keyword(s):  
Solvent Accessibility ◽  
Phylogenetic Signal ◽  
Tree Of Life ◽  
Striking Difference ◽  
Relative Solvent Accessibility ◽  
Animal Evolution ◽  
Phylogenomic Analyses ◽  
Cat Model ◽  
Protein Datasets ◽  
Genome Scale

AbstractPhylogenomics has revolutionized the study of evolutionary relationships. However, genome-scale data have not been able to resolve all relationships in the tree of life. This could reflect the poor-fit of the models used to analyze heterogeneous datasets; that heterogeneity is likely to have many explanations. However, it seems reasonable to hypothesize that the different patterns of selection on proteins based on their structures might represent a source of heterogeneity. To test that hypothesis, we developed an efficient pipeline to divide phylogenomic datasets that comprise proteins into subsets based on secondary structure and relative solvent accessibility. We then tested whether amino acids in different structural environments had different signals for the deepest branches in the metazoan tree of life. Sites located in different structural environments did support distinct tree topologies. The most striking difference in phylogenetic signal reflected relative solvent accessibility; analyses of sites on the surface of proteins yielded a tree that placed ctenophores sister to all other animals whereas sites buried inside proteins yielded a tree with a sponge-ctenophore clade. These differences in phylogenetic signal were not ameliorated when we repeated our analyses using the site-heterogeneous CAT model, a mixture model that is often used for analyses of protein datasets. In fact, analyses using the CAT model actually resulted in rearrangements that are unlikely to represent evolutionary history. These results provide striking evidence that it will be necessary to achieve a better understanding the constraints due to protein structure to improve phylogenetic estimation.

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