Universal Common Ancestor Research Articles

Early Evolution of Transcription Systems and Divergence of Archaea and Bacteria.

DNA template-dependent multi-subunit RNA polymerases (RNAPs) found in all three domains of life and some viruses are of the two-double-Ψ-β-barrel (DPBB) type. The 2-DPBB protein format is also found in some RNA template-dependent RNAPs and a major replicative DNA template-dependent DNA polymerase (DNAP) from Archaea (PolD). The 2−DPBB family of RNAPs and DNAPs probably evolved prior to the last universal common cellular ancestor (LUCA). Archaeal Transcription Factor B (TFB) and bacterial σ factors include homologous strings of helix-turn-helix units. The consequences of TFB-σ homology are discussed in terms of the evolution of archaeal and bacterial core promoters. Domain-specific DPBB loop inserts functionally connect general transcription factors to the RNAP active site. Archaea appear to be more similar to LUCA than Bacteria. Evolution of bacterial σ factors from TFB appears to have driven divergence of Bacteria from Archaea, splitting the prokaryotic domains.

The physiology and evolution of microbial selenium metabolism.

Selenium is an essential trace element whose compounds are widely metabolized by organisms from all three domains of life. Moreover, phylogenetic evidence indicates that selenium species, along with iron, molybdenum, tungsten, and nickel, were metabolized by the last universal common ancestor of all cellular lineages, primarily for the synthesis of the 21st amino acid selenocysteine. Thus, selenium metabolism is both environmentally ubiquitous and a physiological adaptation of primordial life. Selenium metabolic reactions comprise reductive transformations both for assimilation into macromolecules and dissimilatory reduction of selenium oxyanions and elemental selenium during anaerobic respiration. This review offers a comprehensive overview of the physiology and evolution of both assimilatory and dissimilatory selenium metabolism in bacteria and archaea, highlighting mechanisms of selenium respiration. This includes a thorough discussion of our current knowledge of the physiology of selenocysteine synthesis and incorporation into proteins in bacteria obtained from structural biology. Additionally, this is the first comprehensive discussion in a review of the incorporation of selenium into the tRNA nucleoside 5-methylaminomethyl-2-selenouridine and as an inorganic cofactor in certain molybdenum hydroxylase enzymes. Throughout, conserved mechanisms and derived features of selenium metabolism in both domains are emphasized and discussed within the context of the global selenium biogeochemical cycle.

A conserved folding nucleus sculpts the free energy landscape of bacterial and archaeal orthologs from a divergent TIM barrel family

The amino acid sequences of proteins have evolved over billions of years, preserving their structures and functions while responding to evolutionary forces. Are there conserved sequence and structural elements that preserve the protein folding mechanisms? The functionally diverse and ancient (βα)1-8 TIM barrel motif may answer this question. We mapped the complex six-state folding free energy surface of a ∼3.6 billion y old, bacterial indole-3-glycerol phosphate synthase (IGPS) TIM barrel enzyme by equilibrium and kinetic hydrogen-deuterium exchange mass spectrometry (HDX-MS). HDX-MS on the intact protein reported exchange in the native basin and the presence of two thermodynamically distinct on- and off-pathway intermediates in slow but dynamic equilibrium with each other. Proteolysis revealed protection in a small (α1β2) and a large cluster (β5α5β6α6β7) and that these clusters form cores of stability in Ia and Ibp The strongest protection in both states resides in β4α4 with the highest density of branched aliphatic side chain contacts in the folded structure. Similar correlations were observed previously for an evolutionarily distinct archaeal IGPS, emphasizing a key role for hydrophobicity in stabilizing common high-energy folding intermediates. A bioinformatics analysis of IGPS sequences from the three superkingdoms revealed an exceedingly high hydrophobicity and surprising α-helix propensity for β4, preceded by a highly conserved βα-hairpin clamp that links β3 and β4. The conservation of the folding mechanisms for archaeal and bacterial IGPS proteins reflects the conservation of key elements of sequence and structure that first appeared in the last universal common ancestor of these ancient proteins.

Origin and evolution of nonulosonic acid synthases and their relationship with bacterial pathogenicity revealed by a large-scale phylogenetic analysis.

Nonulosonic acids (NulOs) are a group of nine-carbon monosaccharides with different functions in nature. N-acetylneuraminic acid (Neu5Ac) is the most common NulO. It covers the membrane surface of all human cells and is a central molecule in the process of self-recognition via SIGLECS receptors. Some pathogenic bacteria escape the immune system by copying the sialylation of the host cell membrane. Neu5Ac production in these bacteria is catalysed by the enzyme NeuB. Some bacteria can also produce other NulOs named pseudaminic and legionaminic acids, through the NeuB homologues PseI and LegI, respectively. In Opisthokonta eukaryotes, the biosynthesis of Neu5Ac is catalysed by the enzyme NanS. In this study, we used publicly available data of sequences of NulOs synthases to investigate its distribution within the three domains of life and its relationship with pathogenic bacteria. We mined the KEGG database and found 425 NeuB sequences. Most NeuB sequences (58.74 %) from the KEGG orthology database were classified as from environmental bacteria; however, sequences from pathogenic bacteria showed higher conservation and prevalence of a specific domain named SAF. Using the HMM profile we identified 13 941 NulO synthase sequences in UniProt. Phylogenetic analysis of these sequences showed that the synthases were divided into three main groups that can be related to the lifestyle of these bacteria: (I) predominantly environmental, (II) intermediate and (III) predominantly pathogenic. NeuB was widely distributed in the groups. However, LegI and PseI were more concentrated in groups II and III, respectively. We also found that PseI appeared later in the evolutionary process, derived from NeuB. We use this same methodology to retrieve sialic acid synthase sequences from Archaea and Eukarya. A large-scale phylogenetic analysis showed that while the Archaea sequences are spread across the tree, the eukaryotic NanS sequences were grouped in a specific branch in group II. None of the bacterial NanS sequences grouped with the eukaryotic branch. The analysis of conserved residues showed that the synthases of Archaea and Eukarya present a mutation in one of the three catalytic residues, an E134D change, related to a Neisseria meningitidis reference sequence. We also found that the conservation profile is higher between NeuB of pathogenic bacteria and NanS of eukaryotes than between NeuB of environmental bacteria and NanS of eukaryotes. Our large-scale analysis brings new perspectives on the evolution of NulOs synthases, suggesting their presence in the last common universal ancestor.

LUCA to LECA, the Lucacene: A model for the gigayear delay from the first prokaryote to eukaryogenesis

It is puzzling why life on Earth consisted of prokaryotes for up to 2.5 ± 0.5 billion years (Gy) before the appearance of the first eukaryotes. This period, from LUCA (Last Universal Common Ancestor) to LECA (Last Eucaryotic Common Ancestor), we have named the Lucacene, to suggest all prokaryotic descendants of LUCA before the appearance of LECA. Here we present a simple model based on horizontal gene transfer (HGT). It is the process of HGT from Bacteria to Archaea and its reverse that we wish to simulate and estimate its duration until eukaryogenesis. Rough quantitation of its parameters shows that the model may explain the long duration of the Lucacene.

Did Amino Acid Side Chain Reactivity Dictate the Composition and Timing of Aminoacyl-tRNA Synthetase Evolution?

The twenty amino acids in the standard genetic code were fixed prior to the last universal common ancestor (LUCA). Factors that guided this selection included establishment of pathways for their metabolic synthesis and the concomitant fixation of substrate specificities in the emerging aminoacyl-tRNA synthetases (aaRSs). In this conceptual paper, we propose that the chemical reactivity of some amino acid side chains (e.g., lysine, cysteine, homocysteine, ornithine, homoserine, and selenocysteine) delayed or prohibited the emergence of the corresponding aaRSs and helped define the amino acids in the standard genetic code. We also consider the possibility that amino acid chemistry delayed the emergence of the glutaminyl- and asparaginyl-tRNA synthetases, neither of which are ubiquitous in extant organisms. We argue that fundamental chemical principles played critical roles in fixation of some aspects of the genetic code pre- and post-LUCA.

The very early evolution of protein translocation across membranes.

In this study, we used a computational approach to investigate the early evolutionary history of a system of proteins that, together, embed and translocate other proteins across cell membranes. Cell membranes comprise the basis for cellularity, which is an ancient, fundamental organizing principle shared by all organisms and a key innovation in the evolution of life on Earth. Two related requirements for cellularity are that organisms are able to both embed proteins into membranes and translocate proteins across membranes. One system that accomplishes these tasks is the signal recognition particle (SRP) system, in which the core protein components are the paralogs, FtsY and Ffh. Complementary to the SRP system is the Sec translocation channel, in which the primary channel-forming protein is SecY. We performed phylogenetic analyses that strongly supported prior inferences that FtsY, Ffh, and SecY were all present by the time of the last universal common ancestor of life, the LUCA, and that the ancestor of FtsY and Ffh existed before the LUCA. Further, we combined ancestral sequence reconstruction and protein structure and function prediction to show that the LUCA had an SRP system and Sec translocation channel that were similar to those of extant organisms. We also show that the ancestor of Ffh and FtsY that predated the LUCA was more similar to FtsY than Ffh but could still have comprised a rudimentary protein translocation system on its own. Duplication of the ancestor of FtsY and Ffh facilitated the specialization of FtsY as a membrane bound receptor and Ffh as a cytoplasmic protein that could bind nascent proteins with specific membrane-targeting signal sequences. Finally, we analyzed amino acid frequencies in our ancestral sequence reconstructions to infer that the ancestral Ffh/FtsY protein likely arose prior to or just after the completion of the canonical genetic code. Taken together, our results offer a window into the very early evolutionary history of cellularity.

The dyad of the Y-junction- and a flavin module unites diverse redox enzymes

The concomitant presence of two distinctive polypeptide modules, which we have chosen to denominate as the “Y-junction” and the “flavin” module, is observed in 3D structures of enzymes as functionally diverse as complex I, NAD(P)-dependent [NiFe]-hydrogenases and NAD(P)-dependent formate dehydrogenases. Amino acid sequence conservation furthermore suggests that both modules are also part of NAD(P)-dependent [FeFe]-hydrogenases for which no 3D structure model is available yet. The flavin module harbours the site of interaction with the substrate NAD(P) which exchanges two electrons with a strictly conserved flavin moiety. The Y-junction module typically contains four iron-sulphur centres arranged to form a Y-shaped electron transfer conduit and mediates electron transfer between the flavin module and the catalytic units of the respective enzymes. The Y-junction module represents an electron transfer hub with three potential electron entry/exit sites. The pattern of specific redox centres present both in the Y-junction and the flavin module is correlated to present knowledge of these enzymes' functional properties. We have searched publicly accessible genomes for gene clusters containing both the Y-junction and the flavin module to assemble a comprehensive picture of the diversity of enzymes harbouring this dyad of modules and to reconstruct their phylogenetic relationships. These analyses indicate the presence of the dyad already in the last universal common ancestor and the emergence of complex I's EFG-module out of a subgroup of NAD(P)- dependent formate dehydrogenases.

The evolution of oxygen-utilizing enzymes suggests early biosphere oxygenation.

Production of molecular oxygen was a turning point in the Earth's history. The geological record indicates the Great Oxidation Event, which marked a permanent transition to an oxidizing atmosphere around 2.4 Ga. However, the degree to which oxygen was available to life before oxygenation of the atmosphere remains unknown. Here, phylogenetic analysis of all known oxygen-utilizing and -producing enzymes (O2-enzymes) indicates that oxygen became widely available to living organisms well before the Great Oxidation Event. About 60% of the O2-enzyme families whose birth can be dated appear to have emerged at the separation of terrestrial and marine bacteria (22 families, compared to two families assigned to the last universal common ancestor). This node, dubbed the last universal oxygen ancestor, coincides with a burst of emergence of both oxygenases and other oxidoreductases, thus suggesting a wider availability of oxygen around 3.1 Ga.

Origin of Species before Origin of Life: The Role of Speciation in Chemical Evolution.

Speciation, an evolutionary process by which new species form, is ultimately responsible for the incredible biodiversity that we observe on Earth every day. Such biodiversity is one of the critical features which contributes to the survivability of biospheres and modern life. While speciation and biodiversity have been amply studied in organismic evolution and modern life, it has not yet been applied to a great extent to understanding the evolutionary dynamics of primitive life. In particular, one unanswered question is at what point in the history of life did speciation as a phenomenon emerge in the first place. Here, we discuss the mechanisms by which speciation could have occurred before the origins of life in the context of chemical evolution. Specifically, we discuss that primitive compartments formed before the emergence of the last universal common ancestor (LUCA) could have provided a mechanism by which primitive chemical systems underwent speciation. In particular, we introduce a variety of primitive compartment structures, and associated functions, that may have plausibly been present on early Earth, followed by examples of both discriminate and indiscriminate speciation affected by primitive modes of compartmentalization. Finally, we discuss modern technologies, in particular, droplet microfluidics, that can be applied to studying speciation phenomena in the laboratory over short timescales. We hope that this discussion highlights the current areas of need in further studies on primitive speciation phenomena while simultaneously proposing directions as important areas of study to the origins of life.

Reconstituting Natural Cell Elements in Synthetic Cells.

Building a live cell from non-living building blocks would be a fundamental breakthrough in biological sciences, and it would enable engineering new lineages of life, not directly descendant of the Last Universal Common Ancestor. Fully engineered synthetic cells will have architectures that can be radically different from the natural cells, yet most life processes reconstituted in synthetic cells so far are built from natural and biosimilar building blocks. Most natural processes have already been reconstituted in synthetic cell chassis. This paper summarizes recent advancements in using non-living building blocks to reconstitute some of the most crucial features of living systems in a fully engineerable chassis of a synthetic cell.

Subcompartmentalization and Pseudo-Division of Model Protocells

Membrane enclosed intracellular compartments have previously been exclusively associated with the eukaryotes, represented by the highly compartmentalized last eukaryotic common ancestor. Recent evidence showing the presence of membranous compartments with specific functions in archaea and bacteria makes it conceivable that the last universal common ancestor and its hypothetical precursor, the protocell, could have exhibited compartmentalization. To our knowledge, there are no experimental studies yet that have tested this hypothesis.

Origin of Life

The origin of life is one of the most interesting and challenging questions in biology. This article discusses relevant contemporary theories and hypotheses about the origin of life, recent scientific evidence supporting them, and the main contributions of several scientists of different nationalities and specialties in different disciplines. Also discussed are several ideas about the characteristics of the most recent common ancestor, also called the “last universal common ancestor” (or LUCA), including cellular status (unicellular or community) and homogeneity level.

Is it possible that cells have had more than one origin?

Cells occupy a prominent place in the history of life in Earth. The central role of cellular organization can be understood by the fact that “cellular life” is often used as a synonym for life itself. Thus, most characteristics used to define cell overlap with those ones used to define life. However, innovative scenarios for the origin of life are bringing alternative views to describe how cells may have evolved from the open biological systems named progenotes. Here, using a logical and conceptual analysis, we re-evaluate the characteristics used to infer a single origin for cells. We argue that some evidences used to support cell monophyly, such as the presence of elements from the translation mechanism together with the universality of the genetic code, actually indicate a unique origin for all “biological systems”, a term used to define not only cells, but also viruses and progenotes. Besides, we present evidence that at least two biochemical pathways as important as (i) DNA replication and (ii) lipid biosynthesis are not homologous between Bacteria and Archaea. The identities observed between the proteins involved in those pathways along representatives of these two ancestral domains of life are too low to indicate common genic ancestry. Altogether these facts can be seen as an indication that cellular organization has possibly evolved two or more times and that LUCA (the Last Universal Common Ancestor) may not have existed as a cellular entity. Thus, we aim to consider the possibility that different strategies acquired by biological systems to exist, such as viral, bacterial and archaeal were most likely originated independently from the evolution of different progenote populations.

The Hunt for Ancient Prions: Archaeal Prion-Like Domains Form Amyloid-Based Epigenetic Elements.

Prions, proteins that can convert between structurally and functionally distinct states and serve as non-Mendelian mechanisms of inheritance, were initially discovered and only known in eukaryotes, and consequently considered to likely be a relatively late evolutionary acquisition. However, the recent discovery of prions in bacteria and viruses has intimated a potentially more ancient evolutionary origin. Here, we provide evidence that prion-forming domains exist in the domain archaea, the last domain of life left unexplored with regard to prions. We searched for archaeal candidate prion-forming protein sequences computationally, described their taxonomic distribution and phylogeny, and analyzed their associated functional annotations. Using biophysical in vitro assays, cell-based and microscopic approaches, and dye-binding analyses, we tested select candidate prion-forming domains for prionogenic characteristics. Out of the 16 tested, eight formed amyloids, and six acted as protein-based elements of information transfer driving non-Mendelian patterns of inheritance. We also identified short peptides from our archaeal prion candidates that can form amyloid fibrils independently. Lastly, candidates that tested positively in our assays had significantly higher tyrosine and phenylalanine content than candidates that tested negatively, an observation that may help future archaeal prion predictions. Taken together, our discovery of functional prion-forming domains in archaea provides evidence that multiple archaeal proteins are capable of acting as prions-thus expanding our knowledge of this epigenetic phenomenon to the third and final domain of life and bolstering the possibility that they were present at the time of the last universal common ancestor.

Universal and taxon-specific trends in protein sequences as a function of age.

Extant protein-coding sequences span a huge range of ages, from those that emerged only recently to those present in the last universal common ancestor. Because evolution has had less time to act on young sequences, there might be 'phylostratigraphy' trends in any properties that evolve slowly with age. A long-term reduction in hydrophobicity and hydrophobic clustering was found in previous, taxonomically restricted studies. Here we perform integrated phylostratigraphy across 435 fully sequenced species, using sensitive HMM methods to detect protein domain homology. We find that the reduction in hydrophobic clustering is universal across lineages. However, only young animal domains have a tendency to have higher structural disorder. Among ancient domains, trends in amino acid composition reflect the order of recruitment into the genetic code, suggesting that the composition of the contemporary descendants of ancient sequences reflects amino acid availability during the earliest stages of life, when these sequences first emerged.

Jumbo Phages: A Comparative Genomic Overview of Core Functions and Adaptions for Biological Conflicts.

Jumbo phages have attracted much attention by virtue of their extraordinary genome size and unusual aspects of biology. By performing a comparative genomics analysis of 224 jumbo phages, we suggest an objective inclusion criterion based on genome size distributions and present a synthetic overview of their manifold adaptations across major biological systems. By means of clustering and principal component analysis of the phyletic patterns of conserved genes, all known jumbo phages can be classified into three higher-order groups, which include both myoviral and siphoviral morphologies indicating multiple independent origins from smaller predecessors. Our study uncovers several under-appreciated or unreported aspects of the DNA replication, recombination, transcription and virion maturation systems. Leveraging sensitive sequence analysis methods, we identify novel protein-modifying enzymes that might help hijack the host-machinery. Focusing on host–virus conflicts, we detect strategies used to counter different wings of the bacterial immune system, such as cyclic nucleotide- and NAD+-dependent effector-activation, and prevention of superinfection during pseudolysogeny. We reconstruct the RNA-repair systems of jumbo phages that counter the consequences of RNA-targeting host effectors. These findings also suggest that several jumbo phage proteins provide a snapshot of the systems found in ancient replicons preceding the last universal ancestor of cellular life.

The structure and mechanism of the bacterial type II secretion system.

The type II secretion system (T2SS) is a multi-protein complex used by many bacteria to move substrates across their cell membrane. Substrates released into the environment serve as local and long-range effectors that promote nutrient acquisition, biofilm formation, and pathogenicity. In both animals and plants, the T2SS is increasingly recognized as a key driver of virulence. The T2SS spans the bacterial cell envelope and extrudes substrates through an outer membrane secretin channel using a pseudopilus. An inner membrane assembly platform and a cytoplasmic motor controls pseudopilus assembly. This microreview focuses on the structure and mechanism of the T2SS. Advances in cryo-electron microscopy are enabling increasingly elaborate sub-complexes to be resolved. However, key questions remain regarding the mechanism of pseudopilus extension and retraction, and how this is coupled with the choreography of the substrate moving through the secretion system. The T2SS is part of an ancient type IV filament superfamily that may have been present within the last universal common ancestor (LUCA). Overall, mechanistic principles that underlie T2SS function have implication for other closely related systems such as the type IV and tight adherence pilus systems.

The late appearance of DNA, the nature of the LUCA and ancestors of the domains of life

It has been firmly observed that replicative DNA polymerases of bacteria, archaea and eukaryotes are not homologous proteins. This lack of homology in the replication apparatus among the domains of life is not only compatible with but would seem to imply the view that the emergence of DNA occurred in the fundamental cellular lineages. In consequence, this diversity of DNA polymerase would go back to the level of ancestors of the domains of life and to the evolutionary time in which the DNA emerged. Therefore, the presumed evolutionary stage linked to the RNA- > DNA transition would have occurred only at the level of ancestors of the main lineages of the tree of life. Thus, the high noise associated with this major evolutionary transition and the impossibility for a cellular stage to generate different fundamental genetically profound traits - such as the different replication apparatuses of bacteria, archaea and eukaryotes - would imply not only that the last universal common ancestor (LUCA) was a progenote but that the ancestors of the domains of life were also at this evolutionary stage. So, I criticize the hypotheses which want, instead, that completely different cells - such as, bacteria and archaea - could have originated from a cellular LUCA.

On the emergence of P-Loop NTPase and Rossmann enzymes from a Beta-Alpha-Beta ancestral fragment.

This article is dedicated to the memory of Michael G. Rossmann. Dating back to the last universal common ancestor, P-loop NTPases and Rossmanns comprise the most ubiquitous and diverse enzyme lineages. Despite similarities in their overall architecture and phosphate binding motif, a lack of sequence identity and some fundamental structural differences currently designates them as independent emergences. We systematically searched for structure and sequence elements shared by both lineages. We detected homologous segments that span the first βαβ motif of both lineages, including the phosphate binding loop and a conserved aspartate at the tip of β2. The latter ligates the catalytic metal in P-loop NTPases, while in Rossmanns it binds the nucleotide's ribose moiety. Tubulin, a Rossmann GTPase, demonstrates the potential of the β2-Asp to take either one of these two roles. While convergence cannot be completely ruled out, we show that both lineages likely emerged from a common βαβ segment that comprises the core of these enzyme families to this very day.