scholarly journals Reconstructing and Analysing The Genome of The Last Eukaryote Common Ancestor to Better Understand the Transition from FECA to LECA

2019 ◽  
Author(s):  
David Newman ◽  
Fiona J. Whelan ◽  
Matthew Moore ◽  
Martin Rusilowicz ◽  
James O. McInerney
Keyword(s):  
Cell Biology ◽  
Common Ancestor ◽  
Transition Period ◽  
Gene Families ◽  
Post Translational Modification ◽  
Kegg Database ◽  
Cellular Processes ◽  
Eukaryote Evolution ◽  
Genetic Information Processing ◽  
Eukaryotic Genomes

AbstractIt is still a matter of debate whether the First Eukaryote Common Ancestor (FECA) arose from the merger of an archaeal host with an alphaproteobacterium, or was a proto-eukaryote with significant eukaryotic characteristics way before endosymbiosis occurred. The Last Eukaryote Common Ancestor (LECA) as its descendant is thought to be an entity that possessed functional and cellular complexity comparable to modern organisms. The precise nature and physiology of both of these organisms has been a long-standing, unanswered question in evolutionary and cell biology. Recently, a much broader diversity of eukaryotic genomes has become available and this means we can reconstruct early eukaryote evolution with a greater deal of precision. Here, we reconstruct a hypothetical genome for LECA from modern eukaryote genomes. The constituent genes were mapped onto 454 pathways from the KEGG database covering cellular, genetic, and metabolic processes across six model species to provide functional insights into it’s capabilities. We reconstruct a LECA that was a facultatively anaerobic, single-celled organism, similar to a modern Protist possessing complex predatory and sexual behaviour. We go on to examine how much of these capabilities arose along the FECA-to-LECA transition period. We see a at least 1,554 genes gained by FECA during this evolutionary period with extensive remodelling of pathways relating to lipid metabolism, cellular processes, genetic information processing, protein processing, and signalling. We extracted the BRITE classifications for the genes from the KEGG database, which arose during the transition from FECA-to-LECA and examine the types of genes that saw the most gains and what novel classifications were introduced. Two-thirds of our reconstructed LECA genome appears to be prokaryote in origin and the remaining third consists of genes with functional classifications that originate from prokaryote homologs in our LECA genome. Signal transduction and Post Translational Modification elements stand out as the primary novel classes of genes developed during this period. These results suggest that largely the eukaryote common ancestors achieved the defining characteristics of modern eukaryotes by primarily expanding on prokaryote biology and gene families.

scholarly journals The asgardarchaeal-unique contribution to protein families of the eukaryotic common ancestor was 0.3%

2021 ◽  
Author(s):  
Michael Knopp ◽  
Simon Stockhorst ◽  
Mark van der Giezen ◽  
Sriram G. Garg ◽  
Sven B. Gould
Keyword(s):  
Cell Biology ◽  
Common Ancestor ◽  
Unique Contribution ◽  
Clustering Methods ◽  
Protein Families ◽  
Archaeal Lineage ◽  
Specific Proteins ◽  
The Difference ◽  
Coding Capacity ◽  
Eukaryotic Genomes

Significance StatementEver since the first report of a new archaeal lineage, the asgardarchaea, their metagenome analyses have encouraged continued speculations on a type of cell biology ranging between that of prokaryotes and eukaryotes. While it appears a tempting notion, recent microscopic images of an asgardarchaeon suggest otherwise. We inspected the origin of eukaryotic protein families with respect to their distribution across bacteria and archaea. This reveals that the protein families shared exclusively between asgardarchaea and eukaryotes amounts to only 0.3% of the protein families conserved across all eukaryotes. Asgardarchaeal diversity is likely unrivaled across archaea, but their cell biology remains prokaryotic in nature and lends support for the importance of endosymbiosis in evolving eukaryotic traits.SummaryThe difference between pro- and eukaryotic biology is evident in their genomes, cell biology, and evolution of complex and macroscopic body plans. The lack of intermediates between the two types of cells places the endosymbiotic acquisition of the mitochondrion through an archaeal host at the event horizon of eukaryote origin. The identification of eukaryote specific proteins in a new archaeal phylum, the asgardarchaea, has fueled speculations about their cellular complexity, suggesting they could be eukaryote-like. Here we analyzed the coding capacity of 150 eukaryotes, 1000 bacteria, and 226 archaea, including the only cultured member of the asgardarchaea, Candidatus Prometheoarchaeon syntrophicum MK-D1. Established clustering methods that recover endosymbiotic contributions to eukaryotic genomes, recover an asgardarchaeal-unique contribution of a mere 0.3% to protein families present in the last eukaryotic common ancestor, while simultaneously suggesting that asgardarchaeal diversity rivals that of all other archaea combined. Furthermore, we show that the number of homologs shared exclusively between asgardarchaea and eukaryotes is only 27 on average. Genomic and in particular cellular complexity remains a eukaryote-specific feature and, we conclude, is best understood as the archaeal host’s solution to housing an endosymbiont and not as a preparation for obtaining one.

scholarly journals The interactome of Cryptococcus neoformans Rmt5 reveals multiple regulatory points in fungal cell biology and pathogenesis

2022 ◽  
Author(s):  
Murat C Kalem ◽  
Harini Subbiah ◽  
Shichen Shen ◽  
Runpu Chen ◽  
Luke Terry ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Cell Biology ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Arginine Methylation ◽  
Chromosome 9 ◽  
Post Translational Modification ◽  
Cellular Processes ◽  
Carbon Dioxide Atmosphere

Protein arginine methylation is a key post-translational modification in eukaryotes that modulates core cellular processes, including translation, morphology, transcription, and RNA fate. However, this has not been explored in Cryptococcus neoformans, a human-pathogenic basidiomycetous encapsulated fungus. We characterized the five protein arginine methyltransferases in C. neoformans and highlight Rmt5 as critical regulator of cryptococcal morphology and virulence. An rmt5∆ mutant was defective in thermotolerance, had a remodeled cell wall, and exhibited enhanced growth in an elevated carbon dioxide atmosphere and in chemically induced hypoxia. We revealed that Rmt5 interacts with post-transcriptional gene regulators, such as RNA-binding proteins and translation factors. Further investigation of the rmt5∆ mutant showed that Rmt5 is critical for the homeostasis of eIF2α and its phosphorylation state following 3-amino-1,2,4-triazole-induced ribosome stalling. RNA sequencing of one rmt5∆ clone revealed stable chromosome 9 aneuploidy that was ameliorated by complementation but did not impact the rmt5∆ phenotype. As a result of these diverse interactions and functions, loss of RMT5 enhanced phagocytosis by murine macrophages and attenuated disease progression in mice. Taken together, our findings link arginine methylation to critical cryptococcal cellular processes that impact pathogenesis, including post-transcriptional gene regulation by RNA- binding proteins.

scholarly journals Exploitation of the Host Ubiquitin System: Means by Legionella pneumophila

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingjing Luo ◽  
Lidong Wang ◽  
Lei Song ◽  
Zhao-Qing Luo
Keyword(s):  
Legionella Pneumophila ◽  
Cell Biology ◽  
Bacterial Virulence ◽  
Intracellular Pathogen ◽  
Infectious Agents ◽  
Post Translational Modification ◽  
Cellular Processes ◽  
Effective Strategies ◽  
Ubiquitin System ◽  
Common Target

Ubiquitination is a commonly used post-translational modification (PTM) in eukaryotic cells, which regulates a wide variety of cellular processes, such as differentiation, apoptosis, cell cycle, and immunity. Because of its essential role in immunity, the ubiquitin network is a common target of infectious agents, which have evolved various effective strategies to hijack and co-opt ubiquitin signaling for their benefit. The intracellular pathogen Legionella pneumophila represents one such example; it utilizes a large cohort of virulence factors called effectors to modulate diverse cellular processes, resulting in the formation a compartment called the Legionella-containing vacuole (LCV) that supports its replication. Many of these effectors function to re-orchestrate ubiquitin signaling with distinct biochemical activities. In this review, we highlight recent progress in the mechanism of action of L. pneumophila effectors involved in ubiquitination and discuss their roles in bacterial virulence and host cell biology.

scholarly journals Systematic Humanization of the Yeast Cytoskeleton Discerns Functionally Replaceable from Divergent Human Genes

Genetics ◽  
2020 ◽  
Vol 215 (4) ◽  
pp. 1153-1169 ◽  
Author(s):  
Riddhiman K. Garge ◽  
Jon M. Laurent ◽  
Aashiq H. Kachroo ◽  
Edward M. Marcotte
Keyword(s):  
Gene Families ◽  
Growth Defect ◽  
Gene Duplications ◽  
Yeast Gene ◽  
Macromolecular Transport ◽  
Cellular Processes ◽  
Growth Defects ◽  
Yeast Strains ◽  
Human Genes ◽  
Interaction Partners

Many gene families have been expanded by gene duplications along the human lineage, relative to ancestral opisthokonts, but the extent to which the duplicated genes function similarly is understudied. Here, we focused on structural cytoskeletal genes involved in critical cellular processes, including chromosome segregation, macromolecular transport, and cell shape maintenance. To determine functional redundancy and divergence of duplicated human genes, we systematically humanized the yeast actin, myosin, tubulin, and septin genes, testing ∼81% of human cytoskeletal genes across seven gene families for their ability to complement a growth defect induced by inactivation or deletion of the corresponding yeast ortholog. In five of seven families—all but α-tubulin and light myosin, we found at least one human gene capable of complementing loss of the yeast gene. Despite rescuing growth defects, we observed differential abilities of human genes to rescue cell morphology, meiosis, and mating defects. By comparing phenotypes of humanized strains with deletion phenotypes of their interaction partners, we identify instances of human genes in the actin and septin families capable of carrying out essential functions, but failing to fully complement the cytoskeletal roles of their yeast orthologs, thus leading to abnormal cell morphologies. Overall, we show that duplicated human cytoskeletal genes appear to have diverged such that only a few human genes within each family are capable of replacing the essential roles of their yeast orthologs. The resulting yeast strains with humanized cytoskeletal components now provide surrogate platforms to characterize human genes in simplified eukaryotic contexts.

scholarly journals Analysis of the chromosomal clustering of Fusarium-responsive wheat genes uncovers new players in the defence against head blight disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexandre Perochon ◽  
Harriet R. Benbow ◽  
Katarzyna Ślęczka-Brady ◽  
Keshav B. Malla ◽  
Fiona M. Doohan
Keyword(s):  
Map Kinases ◽  
Gene Families ◽  
Gene Clusters ◽  
Head Blight ◽  
Orphan Gene ◽  
Metabolic Genes ◽  
Eukaryotic Gene ◽  
Blight Disease ◽  
Genomic Regions ◽  
Eukaryotic Genomes

AbstractThere is increasing evidence that some functionally related, co-expressed genes cluster within eukaryotic genomes. We present a novel pipeline that delineates such eukaryotic gene clusters. Using this tool for bread wheat, we uncovered 44 clusters of genes that are responsive to the fungal pathogen Fusarium graminearum. As expected, these Fusarium-responsive gene clusters (FRGCs) included metabolic gene clusters, many of which are associated with disease resistance, but hitherto not described for wheat. However, the majority of the FRGCs are non-metabolic, many of which contain clusters of paralogues, including those implicated in plant disease responses, such as glutathione transferases, MAP kinases, and germin-like proteins. 20 of the FRGCs encode nonhomologous, non-metabolic genes (including defence-related genes). One of these clusters includes the characterised Fusarium resistance orphan gene, TaFROG. Eight of the FRGCs map within 6 FHB resistance loci. One small QTL on chromosome 7D (4.7 Mb) encodes eight Fusarium-responsive genes, five of which are within a FRGC. This study provides a new tool to identify genomic regions enriched in genes responsive to specific traits of interest and applied herein it highlighted gene families, genetic loci and biological pathways of importance in the response of wheat to disease.

Semisynthetic triazoles as an approach in the discovery of Novel Lead Compounds

2021 ◽  
Vol 25 ◽  
Author(s):  
Pedro Alves Bezerra Morais ◽  
Carla Santana Francisco ◽  
Heberth de Paula ◽  
Rayssa Ribeiro ◽  
Mariana Alves Eloy ◽  
...  
Keyword(s):  
Natural Products ◽  
Medicinal Chemistry ◽  
Chemical Space ◽  
Biological Activities ◽  
Post Translational Modification ◽  
Cellular Processes ◽  
Modern Drug ◽  
New Chemical Entities ◽  
Almost All ◽  
The 19Th Century

: Historically, the medicinal chemistry is concerned with the approach of organic chemistry to new drug synthesis. Considering the fruitful collections of new molecular entities, the dedicated efforts for medicinal chemistry are rewarding. Planning and search of new and applicable pharmacologic therapies involve the altruistic nature of the scientists. Since the 19th century, notoriously the application of isolated and characterized plant-derived compounds in modern drug discovery and in various stages of clinical development highlight its viability and significance. Natural products influence a broad range of biological processes, covering transcription, translation, and post-translational modification and being effective modulators of almost all basic cellular processes. The research of new chemical entities through “click chemistry” continuously opens up a map for the remarkable exploration of chemical space in towards leading natural products optimization by structure-activity relationship. Finally, here in this review, we expect to gather a broad knowledge involving triazolic natural products derivatives, synthetic routes, structures, and their biological activities.

scholarly journals The split protein phosphatase system

2018 ◽  
Vol 475 (23) ◽  
pp. 3707-3723 ◽  
Author(s):  
Anne Bertolotti
Keyword(s):  
Protein Phosphatase ◽  
Catalytic Subunit ◽  
Regulatory Subunit ◽  
Post Translational Modification ◽  
Antagonistic Action ◽  
Cellular Processes ◽  
Depth Study ◽  
Split Protein ◽  
Phosphatase System ◽  
Physiological Substrates

Reversible phosphorylation of proteins is a post-translational modification that regulates all aspect of life through the antagonistic action of kinases and phosphatases. Protein kinases are well characterized, but protein phosphatases have been relatively neglected. Protein phosphatase 1 (PP1) catalyzes the dephosphorylation of a major fraction of phospho-serines and phospho-threonines in cells and thereby controls a broad range of cellular processes. In this review, I will discuss how phosphatases were discovered, how the view that they were unselective emerged and how recent findings have revealed their exquisite selectivity. Unlike kinases, PP1 phosphatases are obligatory heteromers composed of a catalytic subunit bound to one (or two) non-catalytic subunit(s). Based on an in-depth study of two holophosphatases, I propose the following: selective dephosphorylation depends on the assembly of two components, the catalytic subunit and the non-catalytic subunit, which serves as a high-affinity substrate receptor. Because functional complementation of the two modules is required to produce a selective holophosphatase, one can consider that they are split enzymes. The non-catalytic subunit was often referred to as a regulatory subunit, but it is, in fact, an essential component of the holoenzyme. In this model, a phosphatase and its array of mostly orphan substrate receptors constitute the split protein phosphatase system. The set of potentially generalizable principles outlined in this review may facilitate the study of these poorly understood enzymes and the identification of their physiological substrates.

Functional analysis of the SUMOylation pathway in Drosophila

2008 ◽  
Vol 36 (5) ◽  
pp. 868-873 ◽  
Author(s):  
Ana Talamillo ◽  
Jonatan Sánchez ◽  
Rosa Barrio
Keyword(s):  
Functional Analysis ◽  
Fine Tuning ◽  
Model Systems ◽  
Post Translational Modification ◽  
Reversible Process ◽  
Cellular Processes ◽  
Tuning Mechanism ◽  
Sumo Conjugation

SUMOylation, a reversible process used as a ‘fine-tuning’ mechanism to regulate the role of multiple proteins, is conserved throughout evolution. This post-translational modification affects several cellular processes by the modulation of subcellular localization, activity or stability of a variety of substrates. A growing number of proteins have been identified as targets for SUMOylation, although, for many of them, the role of SUMO conjugation on their function is unknown. The use of model systems might facilitate the study of SUMOylation implications in vivo. In the present paper, we have compiled what is known about SUMOylation in Drosophila melanogaster, where the use of genetics provides new insights on SUMOylation's biological roles.

scholarly journals Structural Insights into Protein Regulation by Phosphorylation and Substrate Recognition of Protein Kinases/Phosphatases

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 957
Author(s):  
Seung-Hyeon Seok
Keyword(s):  
Protein Phosphorylation ◽  
Protein Kinases ◽  
Protein Phosphatases ◽  
Substrate Recognition ◽  
Protein Structures ◽  
Phosphate Group ◽  
Amino Acid Side Chain ◽  
Post Translational Modification ◽  
Cellular Processes ◽  
Structural Insights

Protein phosphorylation is one of the most widely observed and important post-translational modification (PTM) processes. Protein phosphorylation is regulated by protein kinases, each of which covalently attaches a phosphate group to an amino acid side chain on a serine (Ser), threonine (Thr), or tyrosine (Tyr) residue of a protein, and by protein phosphatases, each of which, conversely, removes a phosphate group from a phosphoprotein. These reversible enzyme activities provide a regulatory mechanism by activating or deactivating many diverse functions of proteins in various cellular processes. In this review, their structures and substrate recognition are described and summarized, focusing on Ser/Thr protein kinases and protein Ser/Thr phosphatases, and the regulation of protein structures by phosphorylation. The studies reviewed here and the resulting information could contribute to further structural, biochemical, and combined studies on the mechanisms of protein phosphorylation and to drug discovery approaches targeting protein kinases or protein phosphatases.

scholarly journals The organisation and functions of local Ca2+ signals

2001 ◽  
Vol 114 (12) ◽  
pp. 2213-2222 ◽  
Author(s):  
Martin D. Bootman ◽  
Peter Lipp ◽  
Michael J. Berridge
Keyword(s):  
Cell Proliferation ◽  
Gene Transcription ◽  
Cell Biology ◽  
Building Blocks ◽  
Cell Types ◽  
Diverse Range ◽  
Cellular Processes ◽  
Different Cell Types ◽  
Intracellular Messenger ◽  
Sensory Mechanisms

Calcium (Ca2+) is a ubiquitous intracellular messenger, controlling a diverse range of cellular processes, such as gene transcription, muscle contraction and cell proliferation. The ability of a simple ion such as Ca2+ to play a pivotal role in cell biology results from the facility that cells have to shape Ca2+ signals in space, time and amplitude. To generate and interpret the variety of observed Ca2+ signals, different cell types employ components selected from a Ca2+ signalling ‘toolkit’, which comprises an array of homeostatic and sensory mechanisms. By mixing and matching components from the toolkit, cells can obtain Ca2+ signals that suit their physiology. Recent studies have demonstrated the importance of local Ca2+ signals in defining the specificity of the interaction of Ca2+ with its targets. Furthermore, local Ca2+ signals are the triggers and building blocks for larger global signals that propagate throughout cells.

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