Universal Common Ancestor Of Life Research Articles

Common evolutionary origins of the bacterial glycyl tRNA synthetase and alanyl tRNA synthetase.

Aminoacyl-tRNA synthetases (aaRSs) establish the genetic code. Each aaRS covalently links a given canonical amino acid to a cognate set of tRNA isoacceptors. Glycyl tRNA aminoacylation is unusual in that it is catalyzed by different aaRSs in different lineages of the Tree of Life. We have investigated the phylogenetic distribution and evolutionary history of bacterial glycyl tRNA synthetase (bacGlyRS). This enzyme is found in early diverging bacterial phyla such as Firmicutes, Acidobacteria, and Proteobacteria, but not in archaea or eukarya. We observe relationships between each of six domains of bacGlyRS and six domains of four different RNA-modifying proteins. Component domains of bacGlyRS show common ancestry with (i) the catalytic domain of class II tRNA synthetases; (ii) the HD domain of the bacterial RNase Y; (iii) the body and tail domains of the archaeal CCA-adding enzyme; (iv) the anti-codon binding domain of the arginyl tRNA synthetase; and (v) a previously unrecognized domain that we call ATL (Ancient tRNA latch). The ATL domain has been found thus far only in bacGlyRS and in the universal alanyl tRNA synthetase (uniAlaRS). Further, the catalytic domain of bacGlyRS is more closely related to the catalytic domain of uniAlaRS than to any other aminoacyl tRNA synthetase. The combined results suggest that the ATL and catalytic domains of these two enzymes are ancestral to bacGlyRS and uniAlaRS, which emerged from common protein ancestors by bricolage, stepwise accumulation of protein domains, before the last universal common ancestor of life.

Electron transport chains as a window into the earliest stages of evolution

The origin and early evolution of life is generally studied under two different paradigms: bottom up and top down. Prebiotic chemistry and early Earth geochemistry allow researchers to explore possible origin of life scenarios. But for these “bottom–up” approaches, even successful experiments only amount to a proof of principle. On the other hand, “top–down” research on early evolutionary history is able to provide a historical account about ancient organisms, but is unable to investigate stages that occurred during and just after the origin of life. Here, we consider ancient electron transport chains (ETCs) as a potential bridge between early evolutionary history and a protocellular stage that preceded it. Current phylogenetic evidence suggests that ancestors of several extant ETC components were present at least as late as the last universal common ancestor of life. In addition, recent experiments have shown that some aspects of modern ETCs can be replicated by minerals, protocells, or organic cofactors in the absence of biological proteins. Here, we discuss the diversity of ETCs and other forms of chemiosmotic energy conservation, describe current work on the early evolution of membrane bioenergetics, and advocate for several lines of research to enhance this understanding by pairing top–down and bottom–up approaches.

How did life become cellular?

How did life become cellular?

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 complex phylogenetic relationships of a 4mC/6mA DNA methyltransferase in prokaryotes

DNA methyltransferases are proteins that modify DNA via attachment of methyl groups to nucleobases and are ubiquitous across the bacterial, archaeal, and eukaryotic domains of life. Here, we investigated the complex evolutionary history of the large and consequential 4mC/6mA DNA methyltransferase protein family using phylogenetic reconstruction of amino acid sequences. We present a well-supported phylogeny of this family based on systematic sampling of taxa across superphyla of bacteria and archaea. We compared the phylogeny to a current representation of the species tree of life and found that the 4mC/6mA methyltransferase family has a strikingly complex evolutionary history that likely began sometime after the last universal common ancestor of life diverged into the bacterial and archaeal lineages and probably involved many horizontal gene transfers within and between domains. Despite the complexity of its evolutionary history, we inferred that only one significant shift in molecular evolutionary rate characterizes the diversification of this protein family.

Why is Life the Way it Is?

The concept of the three domains of life (the bacteria, archaea and eukaryotes) goes back to Carl Woese in 1990 1 . Most scientists now see the eukaryotes (cells with a true nucleus) as a secondary domain, derived from bacteria and archaea via an endosymbiosis 2 . That makes the last universal common ancestor of life (LUCA) the ancestor of bacteria and archaea 3 . While these domains are strikingly different in their genetics and biochemistry 4 , they are nearly indistinguishable in their cellular morphology — historically, both groups have been classed as prokaryotes. In terms of their metabolic versatility and molecular machinery, prokaryotes are if anything more sophisticated than eukaryotes 5 . Yet despite an exhaustive search of genetic sequence space in virtually infinite populations over four billion years, neither domain evolved morphological complexity to compare with eukaryotes 5 . The evolutionary path to morphological complexity does not seem to depend on genetic information alone 6 . The most plausible explanation is that physical constraints stemming from the topological structure of prokaryotes blocked the evolution of morphological complexity in prokaryotes, and that the endosymbiosis at the origin of eukaryotes relieved these constraints 6 . In this lecture, I shall argue that the dependence of all life on electrical charges across membranes to generate energy explains the structural constraints on prokaryotes, and the escape from these constraints in eukaryotes 7 .

Ribosomal proteins as documents of the transition from unstructured (poly)peptides to folded proteins.

For the most part, contemporary proteins can be traced back to a basic set of a few thousand domain prototypes, many of which were already established in the Last Universal Common Ancestor of life on Earth, around 3.5 billion years ago. The origin of these domain prototypes, however, remains poorly understood. One hypothesis posits that they arose from an ancestral set of peptides, which acted as cofactors of RNA-mediated catalysis and replication. Initially, these peptides were entirely dependent on the RNA scaffold for their structure, but as their complexity increased, they became able to form structures by excluding water through hydrophobic contacts, making them independent of the RNA scaffold. Their ability to fold was thus an emergent property of peptide-RNA coevolution. The ribosome is the main survivor of this primordial RNA world and offers an excellent model system for retracing the steps that led to the folded proteins of today, due to its very slow rate of change. Close to the peptidyl transferase center, which is the oldest part of the ribosome, proteins are extended and largely devoid of secondary structure; further from the center, their secondary structure content increases and supersecondary topologies become common, although the proteins still largely lack a hydrophobic core; at the ribosomal periphery, supersecondary structures coalesce around hydrophobic cores, forming folds that resemble those seen in proteins of the cytosol. Collectively, ribosomal proteins thus offer a window onto the time when proteins were acquiring the ability to fold.

Models of gene gain and gene loss for probabilistic reconstruction of gene content in the last universal common ancestor of life

BackgroundThe problem of probabilistic inference of gene content in the last common ancestor of several extant species with completely sequenced genomes is: for each gene that is conserved in all or some of the genomes, assign the probability that its ancestral gene was present in the genome of their last common ancestor.ResultsWe have developed a family of models of gene gain and gene loss in evolution, and applied the maximum-likelihood approach that uses phylogenetic tree of prokaryotes and the record of orthologous relationships between their genes to infer the gene content of LUCA, the Last Universal Common Ancestor of all currently living cellular organisms. The crucial parameter, the ratio of gene losses and gene gains, was estimated from the data and was higher in models that take account of the number of in-paralogs in genomes than in models that treat gene presences and absences as a binary trait.ConclusionWhile the numbers of genes that are placed confidently into LUCA are similar in the ML methods and in previously published methods that use various parsimony-based approaches, the identities of genes themselves are different. Most of the models of either kind treat the genes found in many existing genomes in a similar way, assigning to them high probabilities of being ancestral (“high ancestrality”). The ML models are more likely than others to assign high ancestrality to the genes that are relatively rare in the present-day genomes.ReviewersThis article was reviewed by Martijn A Huynen, Toni Gabaldón and Fyodor Kondrashov.

Experimental evidence for the thermophilicity of ancestral life

Theoretical studies have focused on the environmental temperature of the universal common ancestor of life with conflicting conclusions. Here we provide experimental support for the existence of a thermophilic universal common ancestor. We present the thermal stabilities and catalytic efficiencies of nucleoside diphosphate kinases (NDK), designed using the information contained in predictive phylogenetic trees, that seem to represent the last common ancestors of Archaea and of Bacteria. These enzymes display extreme thermal stabilities, suggesting thermophilic ancestries for Archaea and Bacteria. The results are robust to the uncertainties associated with the sequence predictions and to the tree topologies used to infer the ancestral sequences. Moreover, mutagenesis experiments suggest that the universal ancestor also possessed a very thermostable NDK. Because, as we show, the stability of an NDK is directly related to the environmental temperature of its host organism, our results indicate that the last common ancestor of extant life was a thermophile that flourished at a very high temperature.

Some Problems in Proving the Existence of the Universal Common Ancestor of Life on Earth

Although overwhelming circumstantial evidence supports the existence of the universal common ancestor of all extant life on Earth, it is still an open question whether the universal common ancestor existed or not. Theobald (Nature 465, 219–222 (2010)) recently challenged this problem with a formal statistical test applied to aligned sequences of conservative proteins sampled from all domains of life and concluded that the universal common ancestor hypothesis holds. However, we point out that there is a fundamental flaw in Theobald's method which used aligned sequences. We show that the alignment gives a strong bias for the common ancestor hypothesis, and we provide an example that Theobald's method supports a common ancestor hypothesis for two apparently unrelated families of protein-encoding sequences (cytb and nd2 of mitochondria). This arouses suspicion about the effectiveness of the “formal” test.

The Evolution and Structure Prediction of Coiled Coils across All Genomes

Coiled coils are α-helical interactions found in many natural proteins. Various sequence-based coiled-coil predictors are available, but key issues remain: oligomeric state and protein–protein interface prediction and extension to all genomes. We present SpiriCoil ( http://supfam.org/SUPERFAMILY/spiricoil), which is based on a novel approach to the coiled-coil prediction problem for coiled coils that fall into known superfamilies: hundreds of hidden Markov models representing coiled-coil-containing domain families. Using whole domains gives the advantage that sequences flanking the coiled coils help. SpiriCoil performs at least as well as existing methods at detecting coiled coils and significantly advances the state of the art for oligomer state prediction. SpiriCoil has been run on over 16 million sequences, including all completely sequenced genomes (more than 1200), and a resulting Web interface supplies data downloads, alignments, scores, oligomeric state classifications, three-dimensional homology models and visualisation. This has allowed, for the first time, a genomewide analysis of coiled-coil evolution. We found that coiled coils have arisen independently de novo well over a hundred times, and these are observed in 16 different oligomeric states. Coiled coils in almost all oligomeric states were present in the last universal common ancestor of life. The vast majority of occasions that individual coiled coils have arisen de novo were before the last universal common ancestor of life; we do, however, observe scattered instances throughout subsequent evolutionary history, mostly in the formation of the eukaryote superkingdom. Coiled coils do not change their oligomeric state over evolution and did not evolve from the rearrangement of existing helices in proteins; coiled coils were forged in unison with the fold of the whole protein.

Protein content of minimal and ancestral ribosome

Minimal genome approaches seek to define the smallest gene complement compatible with modern-type cellular life on Earth. A consensus of computational and experimental approaches indicates that a minimal genome is close to 300 protein-coding genes, if a rich medium is provided for cell growth. I relate ribosomal gene content in completely sequenced genomes to ribosomal subunit structure and approximate the protein components of the putative minimal ribosome and the ribosome of the Last Universal Common Ancestor of Life. Both sets contain between 35 and 40 proteins. There is evidence of protein-protein and protein-RNA displacement in the evolution of both ribosomal subunits.

The enzymatic methylation of RNA and DNA. I

DNA methyltransferases are proteins that modify DNA via attachment of methyl groups to nucleobases and are ubiquitous across the bacterial, archaeal, and eukaryotic domains of life. Here, we investigated the complex evolutionary history of the large and consequential 4mC/6mA DNA methyltransferase protein family using phylogenetic reconstruction of amino acid sequences. We present a well-supported phylogeny of this family based on systematic sampling of taxa across superphyla of bacteria and archaea. We compared the phylogeny to a current representation of the species tree of life and found that the 4mC/6mA methyltransferase family has a strikingly complex evolutionary history that likely began sometime after the last universal common ancestor of life diverged into the bacterial and archaeal lineages and probably involved many horizontal gene transfers within and between domains. Despite the complexity of its evolutionary history, we inferred that only one significant shift in molecular evolutionary rate characterizes the diversification of this protein family.