Ancestor Of Mitochondria Research Articles

"Candidatus Uabimicrobium helgolandensis"-a planctomycetal bacterium with phagocytosis-like prey cell engulfment, surface-dependent motility, and cell division.

The unique cell biology presented by members of the phylum Planctomycetota has puzzled researchers ever since their discovery. Initially thought to have eukaryotic-like features, their traits are now recognized as exceptional but distinctly bacterial. However, recently discovered strains again added novel and stunning aspects to the planctomycetal cell biology-shapeshifting by members of the "Saltatorellus" clade to an extent that is unprecedented in any other bacterial phylum, and phagocytosis-like cell engulfment in the bacterium "Candidatus Uabimicrobium amorphum." These recent additions to the phylum Planctomycetota indicate hitherto unexplored members with unique cell biology, which we aimed to make accessible for further investigations. Targeting bacteria with features like "Ca. U. amorphum", we first studied both the morphology and behavior of this microorganism in more detail. While similar to eukaryotic amoeboid organisms at first sight, we found "Ca. U. amorphum" to be rather distinct in many regards. Presenting a detailed description of "Ca. U. amorphum," we furthermore found this organism to divide in a fashion that has never been described in any other organism. Employing the obtained knowledge, we isolated a second "bacterium of prey" from the harbor of Heligoland Island (North Sea, Germany). Our isolate shares key features with "Ca. U. amorphum": phagocytosis-like cell engulfment, surface-dependent motility, and the same novel mode of cell division. Being related to "Ca. U. amorphum" within genus thresholds, we propose the name "Ca. Uabimicrobium helgolandensis" for this strain.IMPORTANCE"Candidatus Uabimicrobium helgolandensis" HlEnr_7 adds to the explored bacterial biodiversity with its phagocytosis-like uptake of prey bacteria. Enrichment of this strain indicates that there might be "impossible" microbes out there, missed by metagenomic analyses. Such organisms have the potential to challenge our understanding of nature. For example, the origin of eukaryotes remains enigmatic, with a contentious debate surrounding both the mitochondrial host entity and the moment of uptake. Currently, favored models involve a proteobacterium as the mitochondrial progenitor and an Asgard archaeon as the fusion partner. Models in which a eukaryotic ancestor engulfed the mitochondrial ancestor via phagocytosis had been largely rejected due to bioenergetic constraints. Thus, the phagocytosis-like abilities of planctomycetal bacteria might influence the debate, demonstrating that prey engulfment is possible in a prokaryotic cellular framework.

A somatic view of the genomic impact of mitochondrial endosymbiosis.

The endosymbiosis of mitochondrial ancestors resulted in the transfer of genetic material on an evolutionary scale for eukaryotic species. A new study in PLOS Biology expands this to the genome of somatic cells within individuals and highlights its correlation with aging and disease.

Mitogenomic analysis of a late Pleistocene jaguar from North America.

The jaguar (Panthera onca) is the largest living cat species native to the Americas and one of few large American carnivorans to have survived into the Holocene. However, the extent to which jaguar diversity declined during the end-Pleistocene extinction event remains unclear. For example, Pleistocene jaguar fossils from North America are notably larger than the average extant jaguar, leading to hypotheses that jaguars from this continent represent a now-extinct subspecies (Panthera onca augusta) or species (Panthera augusta). Here, we used a hybridization capture approach to recover an ancient mitochondrial genome from a large, late Pleistocene jaguar from Kingston Saltpeter Cave, Georgia, United States, which we sequenced to 26-fold coverage. We then estimated the evolutionary relationship between the ancient jaguar mitogenome and those from other extinct and living large felids, including multiple jaguars sampled across the species' current range. The ancient mitogenome falls within the diversity of living jaguars. All sampled jaguar mitogenomes share a common mitochondrial ancestor ~400 thousand years ago, indicating that the lineage represented by the ancient specimen dispersed into North America from the south at least once during the late Pleistocene. While genomic data from additional and older specimens will continue to improve understanding of Pleistocene jaguar diversity in the Americas, our results suggest that this specimen falls within the variation of extant jaguars despite the relatively larger size and geographic location and does not represent a distinct taxon.

Natural History of DNA-Dependent DNA Polymerases: Multiple Pathways to the Origins of DNA.

One of the major evolutionary transitions that led to DNA replacing RNA as the primary informational molecule in biological systems is still the subject of an intense debate in the scientific community. DNA polymerases are currently split into various families. Families A, B, and C are the most significant. In bacteria and some types of viruses, enzymes from families A and C predominate, whereas family B enzymes are more common in Archaea, Eukarya, and some types of viruses. A phylogenetic analysis of these three families of DNA polymerase was carried out. We assumed that reverse transcriptase was the ancestor of DNA polymerases. Our findings suggest that families A and C emerged and organized themselves when the earliest bacterial lineages had diverged, and that these earliest lineages had RNA genomes that were in transition-that is, the information was temporally stored in DNA molecules that were continuously being produced by reverse transcription. The origin of DNA and the apparatus for its replication in the mitochondrial ancestors may have occurred independently of DNA and the replication machinery of other bacterial lineages, according to these two alternate modes of genetic material replication. The family C enzymes emerged in a particular bacterial lineage before being passed to viral lineages, which must have functioned by disseminating this machinery to the other lineages of bacteria. Bacterial DNA viruses must have evolved at least twice independently, in addition to the requirement that DNA have arisen twice in bacterial lineages. We offer two possible scenarios based on what we know about bacterial DNA polymerases. One hypothesis contends that family A was initially produced and spread to the other lineages through viral lineages before being supplanted by the emergence of family C and acquisition at that position of the principal replicative polymerase. The evidence points to the independence of these events and suggests that the viral lineage's acquisition of cellular replicative machinery was crucial for the establishment of a DNA genome in the other bacterial lineages, since these viral lineages may have served as a conduit for the machinery's delivery to other bacterial lineages that diverged with the RNA genome. Our data suggest that family B initially established itself in viral lineages and was transferred to ancestral Archaea lineages before the group diversified; thus, the DNA genome must have emerged first in this cellular lineage. Our data point to multiple evolutionary steps in the origins of DNA polymerase, having started off at least twice in the bacterial lineage and once in the archaeal lineage. Given that viral lineages are implicated in a significant portion of the distribution of DNA replication equipment in both bacterial (families A and C) and Archaeal lineages (family A), our data point to a complex scenario.

What can modern bacteria and endosymbionts teach us about eukaryote mitochondria?

In animals, plants and unicellular eukaryotes, mitochondria perform many tasks such as the Krebs cycle, β-oxidation, and oxidative phosphorylation. The “endosymbiotic hypothesis” proposed by Lynn Margulis suggests that this organelle originated from the relationship of an endosymbiotic bacterium and a host-cell. As their relationship evolved, these organisms faced adverse environmental conditions together, each profiting from the other. During coevolution, the endosymbiont transferred genes to the host thus progressing to obligate intracellular and eventually lost all independence, to become a mitochondrion. This organelle shares diverse traits with modern bacteria proving its origin. In addition, modern endosymbiotic bacteria such as Wolbachia sp. and their hosts are coevolving, becoming more interdependent and expressing different metabolic routes in a process that illustrates the pathway that ancient mitochondrial ancestors may have followed.

Intracytoplasmic-membrane development in alphaproteobacteria involves the homolog of the mitochondrial crista-developing protein Mic60

Mitochondrial cristae expand the surface area of respiratory membranes and ultimately allow for the evolutionary scaling of respiration with cell volume across eukaryotes. The discovery of Mic60 homologs among alphaproteobacteria, the closest extant relatives of mitochondria, suggested that cristae might have evolved from bacterial intracytoplasmic membranes (ICMs). Here, we investigated the predicted structure and function of alphaproteobacterial Mic60, and a protein encoded by an adjacent gene Orf52, in two distantly related purple alphaproteobacteria, Rhodobacter sphaeroides and Rhodopseudomonas palustris. In addition, we assessed the potential physical interactors of Mic60 and Orf52 in R.sphaeroides. We show that the three α helices of mitochondrial Mic60's mitofilin domain, as well as its adjacent membrane-binding amphipathic helix, are present in alphaproteobacterial Mic60. The disruption of Mic60 and Orf52 caused photoheterotrophic growth defects, which are most severe under low light conditions, and both their disruption and overexpression led to enlarged ICMs in both studied alphaproteobacteria. We also found that alphaproteobacterial Mic60 physically interacts with BamA, the homolog of Sam50, one of the main physical interactors of eukaryotic Mic60. This interaction, responsible for making contact sites at mitochondrial envelopes, has been conserved in modern alphaproteobacteria despite more than a billion years of evolutionary divergence. Our results suggest a role for Mic60 in photosynthetic ICM development and contact site formation at alphaproteobacterial envelopes. Overall, we provide support for the hypothesis that mitochondrial cristae evolved from alphaproteobacterial ICMs and have therefore improved our understanding of the nature of the mitochondrial ancestor.

On the origin of mitochondria: a multilayer network approach.

The endosymbiotic theory is widely accepted to explain the origin of mitochondria from a bacterial ancestor. While ample evidence supports the intimate connection of Alphaproteobacteria to the mitochondrial ancestor, pinpointing its closest relative within sampled Alphaproteobacteria is still an open evolutionary debate. Many different phylogenetic methods and approaches have been used to answer this challenging question, further compounded by the heterogeneity of sampled taxa, varying evolutionary rates of mitochondrial proteins, and the inherent biases in each method, all factors that can produce phylogenetic artifacts. By harnessing the simplicity and interpretability of protein similarity networks, herein we re-evaluated the origin of mitochondria within an enhanced multilayer framework, which is an extension and improvement of a previously developed method. We used a dataset of eight proteins found in mitochondria (N = 6 organisms) and bacteria (N = 80 organisms). The sequences were aligned and resulting identity matrices were combined to generate an eight-layer multiplex network. Each layer corresponded to a protein network, where nodes represented organisms and edges were placed following mutual sequence identity. The Multi-Newman-Girvan algorithm was applied to evaluate community structure, and bifurcation events linked to network partition allowed to trace patterns of divergence between studied taxa. In our network-based analysis, we first examined the topology of the 8-layer multiplex when mitochondrial sequences disconnected from the main alphaproteobacterial cluster. The resulting topology lent firm support toward an Alphaproteobacteria-sister placement for mitochondria, reinforcing the hypothesis that mitochondria diverged from the common ancestor of all Alphaproteobacteria. Additionally, we observed that the divergence of Rickettsiales was an early event in the evolutionary history of alphaproteobacterial clades. By leveraging complex networks methods to the challenging question of circumscribing mitochondrial origin, we suggest that the entire Alphaproteobacteria clade is the closest relative to mitochondria (Alphaproteobacterial-sister hypothesis), echoing recent findings based on different datasets and methodologies.

Multiple introgressions shape mitochondrial evolutionary history in Drosophila paulistorum and the Drosophila willistoni group

Hybridization and the consequent introgression of genomic elements is an important source of genetic diversity for biological lineages. This is particularly evident in young clades in which hybrid incompatibilities are still incomplete and mixing between species is more likely to occur. Drosophila paulistorum, a representative of the Neotropical Drosophila willistoni subgroup, is a classic model of incipient speciation. The species is divided into six semispecies that show varying degrees of pre- and post-mating incompatibility with each other. In the present study, we investigate the mitochondrial evolutionary history of D. paulistorum and the willistoni subgroup. For that, we perform phylogenetic and comparative analyses of the complete mitochondrial genomes and draft nuclear assemblies of 25 Drosophila lines of the willistoni and saltans species groups. Our results show that the mitochondria of D. paulistorum are polyphyletic and form two non-sister clades that we name α and β. Identification and analyses of nuclear mitochondrial insertions further reveal that the willistoni subgroup has an α-like mitochondrial ancestor and strongly suggest that both the α and β mitochondria of D. paulistorum were acquired through introgression from unknown fly lineages of the willistoni subgroup. We also uncover multiple mitochondrial introgressions across D. paulistorum semispecies and generate novel insight into the evolution of the species.

Enigmatic Evolutionary History of Porphobilinogen Deaminase in Eukaryotic Phototrophs.

Simple SummaryThe heme pathway is essential for most of cellular life. In eukaryotic phototrophs, the entire pathway is plastid localized. Despite that, the enzyme responsible for the synthesis of hydroxymethylbilane, porphobilinogen deaminase, shows α-proteobacterial instead of expected cyanobacterial origins in rhodophytes, chlorophytes, plants, and most algae with complex plastid. However, no such enzyme has been found in the supposed partners of plastid endosymbioses, the heterotrophic eukaryotes, and cyanobacteria. I propose two scenarios explaining this phenomenon by either endosymbiotic gene transfer from the ancestor of mitochondria or a non-endosymbiotic lateral gene transfer from unspecified α-proteobacterium. Phylogenetic analysis of porphobilinogen deaminases does not reject any of the two proposed evolutionary scenarios.In most eukaryotic phototrophs, the entire heme synthesis is localized to the plastid, and enzymes of cyanobacterial origin dominate the pathway. Despite that, porphobilinogen deaminase (PBGD), the enzyme responsible for the synthesis of hydroxymethybilane in the plastid, shows phylogenetic affiliation to α-proteobacteria, the supposed ancestor of mitochondria. Surprisingly, no PBGD of such origin is found in the heme pathway of the supposed partners of the primary plastid endosymbiosis, a primarily heterotrophic eukaryote, and a cyanobacterium. It appears that α-proteobacterial PBGD is absent from glaucophytes but is present in rhodophytes, chlorophytes, plants, and most algae with complex plastids. This may suggest that in eukaryotic phototrophs, except for glaucophytes, either the gene from the mitochondrial ancestor was retained while the cyanobacterial and eukaryotic pseudoparalogs were lost in evolution, or the gene was acquired by non-endosymbiotic gene transfer from an unspecified α-proteobacterium and functionally replaced its cyanobacterial and eukaryotic counterparts.

Symbiotic Models for Reconstruction of Organellogenesis

Various groups of proteobacteria and cyanobacteria, as well as unicellular algae capable of endosymbioses with eukaryotes, are addressed as the models for reconstruction of organellogenesis (transformation of symbiotic microbes into cellular organelles) as a major result of symbiogenesis—the evolution based on formation of integral hereditary systems by tightly interacting partners. Organellogenesis includes the following transitions: facultative non-inherited intracellular symbionts → obligatory inherited endocytobionts → genome-containing organelles → genome-free organelles. We have demonstrated that organellogenesis is accompanied by the loss of bacterial genetic individuality—the ability to maintain and express their own genomes, including their complete elimination. Comparative analysis of various groups of endosymbiotic bacteria showed that the major prerequisite for their transformation into organelles (primary organellogenesis) is high genomic plasticity expressed at the early stages of organellogenesis, under facultative or obligatory dependences on hosts. It is manifested as a directed change in genome architecture (transitions of unitary-type genomes to multicomponent- and reduced-type genomes), as well as in the export of functionally active genes into nonrelated organisms. These properties are characteristic for α-proteobacteria and cyanobacteria—the ancestors of mitochondria and plastids, but not for β- and γ-proteobacteria, Bacteroidetes and Firmicutes, which, although they include multiple endosymbiotic forms, have not been transformed into organelles. A convenient model for analyzing the secondary organellogenesis implemented by eukaryotic microorganisms is represented by dinoflagellates Symbiodinium (Alveolata), which (1) harbor chloroplasts derived from red algae and (2) develop intracellular symbioses with invertebrates behaving as their plastids. Reconstruction of organellogenesis allows us to address the early stages of organic evolution including the trade-off between metabolism and heredity, as well as between the RNA- or DNA-based genomes.

The Plant Mitochondrial TAT Pathway Is Essential for Complex III Biogenesis.

Twin arginine translocation (TAT) pathways have been extensively studied in bacteria and chloroplasts for their role in membrane translocation of folded proteins. However, an increasing number of organisms have been found to contain mitochondria-located TAT subunits, including plant mitochondria, which contain TAT subunits, though in an unusualarrangement with only TatB and TatC subunits. To date, no confirmed function has been attributed to mitochondrial TAT pathways in any organism. Using a truncation mutant approach, we demonstrate that the plant mitochondrial TatB (MTTATB) is required for complex III biogenesis. More specifically, MTTATB performs at a late stage in complex III biogenesis, conveying the translocation of the C terminus of the Rieske FeS subunit back across the inner membrane. This work confirms that plant mitochondria retained a functional TAT pathway for theRieske FeS translocation, most likely from the original mitochondrial ancestor. It is hypothesized thatthe original mitochondria contained a bacteria-derived TAT pathway required for at least the Rieske FeS translocation. In several eukaryotic lineages, this mitochondrial TAT pathway was lost and replaced byBCS1. Interestingly, plant mitochondria appear to assemble complex III in the same subunit order as yeast and mammals but in contrast use bacteria-like assembly factors for this process.

Evolution: Two Domains of Life or Three?

That Bacteria, Archaea and Eukarya (eukaryotes) represent three separate domains of Life, no one having evolved from within any other, has been taken as fact for three decades. Recent work shows this to be untrue. Eukarya arose from well within Archaea and are specifically related to newly discovered archaeal species with eukaryote-like features.

Remote homology searches identify bacterial homologues of eukaryotic lipid transfer proteins, including Chorein-N domains in TamB and AsmA and Mdm31p

BackgroundAll cells rely on lipids for key functions. Lipid transfer proteins allow lipids to exit the hydrophobic environment of bilayers, and cross aqueous spaces. One lipid transfer domain fold present in almost all eukaryotes is the TUbular LIPid binding (TULIP) domain. Three TULIP families have been identified in bacteria (P47, OrfX2 and YceB), but their homology to eukaryotic proteins is too low to specify a common origin. Another recently described eukaryotic lipid transfer domain in VPS13 and ATG2 is Chorein-N, which has no known bacterial homologues. There has been no systematic search for bacterial TULIPs or Chorein-N domains.ResultsRemote homology predictions for bacterial TULIP domains using HHsearch identified four new TULIP domains in three bacterial families. DUF4403 is a full length pseudo-dimeric TULIP with a 6 strand β-meander dimer interface like eukaryotic TULIPs. A similar sheet is also present in YceB, suggesting it homo-dimerizes. TULIP domains were also found in DUF2140 and in the C-terminus DUF2993. Remote homology predictions for bacterial Chorein-N domains identified strong hits in the N-termini of AsmA and TamB in diderm bacteria, which are related to Mdm31p in eukaryotic mitochondria. The N-terminus of DUF2993 has a Chorein-N domain adjacent to its TULIP domain.ConclusionsTULIP lipid transfer domains are widespread in bacteria. Chorein-N domains are also found in bacteria, at the N-terminus of multiple proteins in the intermembrane space of diderms (AsmA, TamB and their relatives) and in Mdm31p, a protein that is likely to have evolved from an AsmA/TamB-like protein in the endosymbiotic mitochondrial ancestor. This indicates that both TULIP and Chorein-N lipid transfer domains may have originated in bacteria.

Melatonin in the evolution of plants and other phototrophs

Melatonin
 is present in numerous phototrophic eukaryotes, not only in plants in the
 meaning of Archaeplastida or of Viridiplantae. It is also formed in members of
 other superclades, such as Excavata and SAR clade. Typically, their respective
 phototrophs have acquired chloroplasts from phototrophic eukaryotes, either by
 taking them up as endosymbionts or by chloroplast capturing. It has been the
 aim of this overview to trace the phylogenetic relationships between the
 various phototrophs according to actual, genetically based taxonomy. This
 includes the consideration of primary heterotrophs that also exist within the
 same groups and some secondary heterotrophs that have lost functional
 chloroplasts. The presence of melatonin in these different taxa is discussed
 under the aspects of its cyanobacterial or α-proteobacterial origins, as
 transmitted by plastidial or mitochondrial ancestors, or by horizontal gene
 transfer. Peculiarities of melatonin metabolism that have evolved in some of
 these groups are also addressed.

Chimeric Structure of Plant Malic Enzyme Family: Different Evolutionary Scenarios for NAD- and NADP-Dependent Isoforms.

Malic enzyme (ME) comprises a family of proteins with multiple isoforms located in different compartments of eukaryotic cells. In plants, cytosolic and plastidic enzymes share several characteristics such as NADP specificity (NADP-ME), oxaloacetate decarboxylase (OAD) activity, and homo-oligomeric assembly. However, mitochondrial counterparts are NAD-dependent proteins (mNAD-ME) lacking OAD activity, which can be structured as homo- and hetero-oligomers of two different subunits. In this study, we examined the molecular basis of these differences using multiple sequence analysis, structural modeling, and phylogenetic approaches. Plant mNAD-MEs show the lowest identity values when compared with other eukaryotic MEs with major differences including short amino acid insertions distributed throughout the primary sequence. Some residues in these exclusive segments are co-evolutionarily connected, suggesting that they could be important for enzymatic functionality. Phylogenetic analysis indicates that eukaryotes from different kingdoms used different strategies for acquiring the current set of NAD(P)-ME isoforms. In this sense, while the full gene family of vertebrates derives from the same ancestral gene, plant NADP-ME and NAD-ME isoforms have a distinct evolutionary history. Plant NADP-ME genes may have arisen from the α-protobacterial-like mitochondrial ancestor, a characteristic shared with major eukaryotic taxa. On the other hand, plant mNAD-ME genes were probably gained through an independent process involving the Archaeplastida ancestor. Finally, several residue signatures unique to all plant mNAD-MEs could be identified, some of which might be functionally connected to their exclusive biochemical properties. In light of these results, molecular evolutionary scenarios for these widely distributed enzymes in plants are discussed.

Eukaryote specific folds: Part of the whole.

The origin of eukaryotes is one of the central transitions in the history of life; without eukaryotes there would be no complex multicellular life. The most accepted scenarios suggest the endosymbiosis of a mitochondrial ancestor with a complex archaeon, even though the details regarding the host and the triggering factors are still being discussed. Accordingly, phylogenetic analyses have demonstrated archaeal affiliations with key informational systems, while metabolic genes are often related to bacteria, mostly to the mitochondrial ancestor. Despite of this, there exists a large number of protein families and folds found only in eukaryotes. In this study, we have analyzed structural superfamilies and folds that probably appeared during eukaryogenesis. These folds typically represent relatively small binding domains of larger multidomain proteins. They are commonly involved in biological processes that are particularly complex in eukaryotes, such as signaling, trafficking/cytoskeleton, ubiquitination, transcription and RNA processing, but according to recent studies, these processes also have prokaryotic roots. Thus the folds originating from an eukaryotic stem seem to represent accessory parts that have contributed in the expansion of several prokaryotic processes to a new level of complexity. This might have taken place as a co-evolutionary process where increasing complexity and fold innovations have supported each other.

Deep mitochondrial origin outside the sampled alphaproteobacteria.

Mitochondria are ATP-generating organelles, the endosymbiotic origin of which was a key event in the evolution of eukaryotic cells 1 . Despite strong phylogenetic evidence that mitochondria had an alphaproteobacterial ancestry 2 , efforts to pinpoint their closest relatives among sampled alphaproteobacteria have generated conflicting results, complicating detailed inferences about the identity and nature of the mitochondrial ancestor. While most studies support the idea that mitochondria evolved from an ancestor related to Rickettsiales3-9, an order that includes several host-associated pathogenic and endosymbiotic lineages10,11, others have suggested that mitochondria evolved from a free-living group12-14. Here we re-evaluate the phylogenetic placement of mitochondria. We used genome-resolved binning of oceanic metagenome datasets and increased the genomic sampling of Alphaproteobacteria with twelve divergent clades, and one clade representing a sister group to all Alphaproteobacteria. Subsequent phylogenomic analyses that specifically address long branch attraction and compositional bias artefacts suggest that mitochondria did not evolve from Rickettsiales or any other currently recognized alphaproteobacterial lineage. Rather, our analyses indicate that mitochondria evolved from a proteobacterial lineage that branched off before the divergence of all sampled alphaproteobacteria. In light of this new result, previous hypotheses on the nature of the mitochondrial ancestor6,15,16 should be re-evaluated.

Disintegrating over space and time: Paraphyly and species delimitation in the Wehrle's Salamander complex

Accurate species delimitation is critical for biodiversity studies. However, species complexes characterized by introgression, high levels of population structure and subtle phenotypic differentiation can be challenging to delimit. Here, we report on a molecular systematic investigation of the woodland salamanders Plethodon wehrlei and Plethodon punctatus, which traditionally have been placed in the Plethodon wehrlei species group. To quantify patterns of genetic variation, we collected genetic samples from throughout the range of both species, including 22 individuals from nine populations of P. punctatus, and 60 individuals from 26 populations of P. wehrlei. From these samples, we sequenced three mtDNA loci (5596 base pairs) and five nuclear loci (3377 base pairs). We inferred time‐calibrated gene trees and species trees using BEAST 2.4.6, and we delimited putative species using a Bayesian implementation of the general mixed Yule‐coalescent model (bGMYC) and STRUCTURE. Finally, we validated putative species using the multispecies coalescent as implemented in Bayesian Phylogenetics and Phylogeography (BPP). We found substantial phylogeographic diversity in P. wehrlei, including multiple geographically cohesive clades and an inferred mitochondrial common ancestor at 11.5 myr (95% HPD: 9.6–13.6 myr) that separated populations formerly assigned to P. dixi from all other populations. We also found that P. punctatus is deeply nested within P. wehrlei, rendering the latter paraphyletic. After discussing the challenges faced by modern species delimitation methods, we recommend retaining P. punctatus because it is ecologically and phenotypically distinct. We further recommend that P. dixi be recognized as a valid species.

Posttranslational arginylation enzyme Ate1 is a mitochondrial‐derived master regulator that coordinates glycolysis and respiration in the Warburg effect

In the Warburg effect observed in vast majority of cancer cells, glycolysis is preferred over mitochondrial respiration. However, the role of mitochondria and its relationship with glycolysis in cancer metabolism is poorly understood. Arginyltransferase 1(Ate1) is an evolutionarily conserved enzyme that exist in most eukaryotes and a large subset of bacteria. In eukaryotes, this enzyme mediates arginylation, the posttranslational addition of one extra arginine to a protein. Recently, Ate1 was identified to be down‐regulated in many types of cancer but the significance of such observation remained unclear. Here, by examining classic glycolytic markers such glucose intake rate, sensitivity to glucose starvation, lactate generation, and the effects of glycolysis inhibitors including 2‐DG and 2‐FDG, we found that a deletion of Ate1 gene is sufficient to causes the Warburg effect on the cell level. This effect was reproduced by shRNA‐mediated knockdown of Ate1 and can be reversed by the expression of a recombinant Ate1 in the KO cells. In a screening of typical players involved in glycolysis, we found that the deletion of Ate1 increases of the protein level of hypoxia‐inducible factor 1a (HIF1a), a protein with known role in glycolysis. We found that the knockdown of HIF1a in Ate1‐KO cells was sufficient to reverse the glycolytic phenoytype in these cells, suggesting Ate1 regulates glycolysis through HIF1a. Furthermore, we found that Ate1 regulates the protein level of HIF1a through both conventional and unconventional pathways. In particularly, HIF1a appears to be a previous unknown substrate of Ate1‐mediated arginylation, which promotes the degradation of HIF1a through the N‐end rule. In addition, the deletion of Ate1 generate prominent effects on the morphology and functions of mitochondria, with significant defect on the assembly of mitochondrial complex II and a consequential accumulation of succinate, which is expected to stabilize the HIF1a protein by an inhibition of the PHD proteins. Finally, we found that eukaryotic Ate1 has significant homology to its counterpart in alpha‐proteobacteria, the ancestor of mitochondria. Also, although the majority of Ate1 is located in the cytosol, a detectable portion of Ate1 is located inside mitochondria. These evidence suggest that the Ate1 enzyme was derived from a gene transfer during the domestication of mitochondria, which further explains the previous unknown role of Ate1 as a master regulator of the balance between glycolysis and mitochondrial function.In summary, our study discovered a novel regulator of cell metabolism with a evolution root concomitant with mitochondria and our data suggest this regulator coordinates the balance between glycolysis and mitochondrial respiration in the cancer Warburg effect. Our data also reveal the existence of a non‐canonical degradation pathway of HIF1a.Support or Funding InformationNIGMS R01 GM107333This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Farming the mitochondrial ancestor as a model of endosymbiotic establishment by natural selection

The origin of mitochondria was a major evolutionary transition leading to eukaryotes, and is a hotly debated issue. It is unknown whether mitochondria were acquired early or late, and whether it was captured via phagocytosis or syntrophic integration. We present dynamical models to directly simulate the emergence of mitochondria in an ecoevolutionary context. Our results show that regulated farming of prey bacteria and delayed digestion can facilitate the establishment of stable endosymbiosis if prey-rich and prey-poor periods alternate. Stable endosymbiosis emerges without assuming any initial metabolic benefit provided by the engulfed partner, in a wide range of parameters, despite that during good periods farming is costly. Our approach lends support to the appearance of mitochondria before any metabolic coupling has emerged, but after the evolution of primitive phagocytosis by the urkaryote.