Modern Descendants Research Articles

Molecular complementarity between simple, universal molecules and ions limited phenotype space in the precursors of cells.

BackgroundFundamental problems faced by the protocells and their modern descendants include how to go from one phenotypic state to another; escape from a basin of attraction in the space of phenotypes; reconcile conflicting growth and survival strategies (and thereby live on ‘the scales of equilibria’); and create a coherent, reproducible phenotype from a multitude of constituents.Presentation of the hypothesisThe solutions to these problems are likely to be found with the organic and inorganic molecules and inorganic ions that constituted protocells, which we term SUMIs for Simple Universal Molecules and Ions. These SUMIs probably included polyphosphate (PolyP) as a source of energy and of phosphate; poly-(R)-3-hydroxybutyrate (PHB) as a source of carbon and as a transporter in association with PolyP; polyamines as a source of nitrogen; lipids as precursors of membranes; as well as peptides, nucleic acids, and calcium. Here, we explore the hypothesis that the direct interactions between PHB, PolyP, polyamines and lipids – modulated by calcium – played a central role in solving the fundamental problems faced by early and modern cells.Testing the hypothesisWe review evidence that SUMIs (1) were abundant and available to protocells; (2) are widespread in modern cells; (3) interact with one another and other cellular constituents to create structures with new functions surprisingly similar to those of proteins and RNA; (4) are essential to creating coherent phenotypes in modern bacteria. SUMIs are therefore natural candidates for reducing the immensity of phenotype space and making the transition from a “primordial soup” to living cells.Implications of the hypothesisWe discuss the relevance of the SUMIs and their interactions to the ideas of molecular complementarity, composomes (molecular aggregates with hereditary properties based on molecular complementarity), and a prebiotic ecology of co-evolving populations of composomes. In particular, we propose that SUMIs might limit the initial phenotype space of composomes in a coherent way. As examples, we propose that acidocalcisomes arose from interactions and self-selection among SUMIs and that the phosphorylation of proteins in modern cells had its origin in the covalent modification of proteins by PHB.ReviewersThis article was reviewed by Doron Lancet and Kepa Ruiz-Mirazo.

EVIDENCE FOR BIOGENIC COPPER (HEMOCYANIN) IN THE MIDDLE CAMBRIAN ARTHROPOD MARRELLA FROM THE BURGESS SHALE

Beginning with the discovery of the middle Cambrian Burgess Shale, the rare examples of exceptional preservation of soft tissues in fine-grained strata have been celebrated as windows into the diversity and complexity of ancient marine animal life. Even so, with the loss of original organic compounds, the physiological attributes of the fossils can be inferred only on the basis of modern descendants or sister groups among extant representatives that can serve as analogs. To test whether soft-bodied fossils from the Burgess Shale and similar Cambrian Lagerstatten could preserve chemical evidence of their original biology, a number of specimens from different groups were analyzed with synchrotron-based X-ray fluorescence imaging to determine the spatial distribution of a range of elements, especially those in exceedingly trace amounts that cannot be detected by more conventional analytical methods. The relative distribution of common elements like Fe, K, Ti, and Ca is related to the composition of the host shale, abundance of pyrite, and presence or absence of preserved exoskeletal calcite. However, the black stain commonly preserved with the arthropod Marrella splendens is preferentially enriched in Cu due to localized residue in the carbon and minute crystals of chalcopyrite. This is interpreted as indicative of the original chemical composition of a primary biotic fluid, likely blood. Since modern-day arthropods generally utilize Cu-containing hemocyanin for oxygen transport, it is hypothesized that hemocyanin was the biogenic source of the observed Cu. This is the first chemical evidence for blood composition in the invertebrate fossil record. These observations reinforce the consensus molecular clock age for the hemocyanin gene family, which traces its origins back to the ‘Cambrian explosion’, thus providing evidence for the early origin of this oxygen carrier among some arthropod groups.

Feasibility of observing Hanbury Brown and Twiss phase

The interferometers of Hanbury Brown and collaborators in the 1950s and 60s, and their modern descendants now being developed (intensity interferometers) measure the spatial power spectrum of the source from intensity correlations at two points. The quantum optical theory of the Hanbury Brown and Twiss (HBT) effect shows that more is possible, in particular the phase information can be recovered by correlating intensities at three points (bispectrum). In this paper we argue that such 3 point measurements are possible for bright stars such as Sirius and Betelgeuse using off the shelf single photon counters with collecting areas of the order of 100m2. It seems possible to map individual features on the stellar surface. Simple diameter measurements would be possible with amateur class telescopes.

Evolution of conformational dynamics determines the conversion of a promiscuous generalist into a specialist enzyme.

β-Lactamases are produced by many modern bacteria as a mechanism of resistance toward β-lactam antibiotics, the most common antibiotics in use. β-Lactamases, however, are ancient enzymes that originated billions of years ago. Recently, proteins corresponding to 2- to 3-Gy-old Precambrian nodes in the evolution of Class A β-lactamases have been prepared and shown to be moderately efficient promiscuous catalysts, able to degrade a variety of antibiotics with catalytic efficiency levels similar to those of an average modern enzyme. Remarkably, there are few structural differences (in particular at the active-site regions) between the resurrected enzymes and a penicillin-specialist modern β-lactamase. Here, we propose that the ancestral promiscuity originates from conformational dynamics. We investigate the differences in conformational dynamics of the ancient and extant β-lactamases through MD simulations and quantify the contribution of each position to functionally related dynamics through Dynamic Flexibility Index. The modern TEM-1 lactamase shows a comparatively rigid active-site region, likely reflecting adaptation for efficient degradation of a specific substrate (penicillin), whereas enhanced deformability at the active-site neighborhood in the ancestral resurrected proteins likely accounts for the binding and subsequent degradation of antibiotic molecules of different size and shape. Clustering of the conformational dynamics on the basis of Principal Component Analysis is in agreement with the functional divergence, as the ancient β-lactamases cluster together, separated from their modern descendant. Finally, our analysis leads to testable predictions, as sites of potential relevance for the evolution of dynamics are identified and mutations at those sites are expected to alter substrate-specificity.

Uncertainty Quantification in Materials Modeling

The Institute for Mathematics and its Applications (IMA) at the University of Minnesota hosted the workshop, ‘‘Uncertainty Quantification in Materials Modeling’’ on December 16–17, 2013. The workshop convened 30 scientists specializing in materials modeling and simulation and researchers in uncertainty quantification (UQ) with the goal of identifying challenges in UQ for materials applications. The following discussion is a summary of workshop findings as well as an invitation to participate in an ambitious follow-up activity tentatively scheduled for summer 2015.* The workshop objectives may be better understood in the context of the Materials Genome Initiative (MGI), which was formally announced by President Barack Obama in June 2011. This ambitious multi-agency program seeks to accelerate the introduction of novel materials into industrial products, striving to reduce by factors of two both the time and cost from discovery to deployment. The initiative proposes creation of a new Materials Innovation Infrastructure as the principal means to achieve this end. This infrastructure will consist of an integrated collection of experimental data and simulation software. These two sources of materials information—experiment and computation—will be seamlessly integrated using data informatics tools tailored for material science communities. The result will be a set of shared, community resources facilitating rapid access to data and numerical simulations on demand. While all elements of this innovation infrastructure will require investments for their research and development, the IMA workshop focused on the role of numerical simulation in material science and engineering. It is natural to expect that increased reliance on computational tools to design and assess materials in silico will enable rapid and relatively inexpensive exploration of design possibilities. That being said, critical assessment of simulation outputs is a prerequisite to promote understanding and trust in the capabilities of simulation for industrial decision making. Uncertainty quantification is an umbrella term that refers to the diverse analysis methods and tools suitable for critical assessment of models and simulations. Elements of UQ analysis include verification and validation (V&V), sensitivity analysis, and uncertainty propagation. For completeness we briefly define these terms here and refer to the recent report by the National Research Council and the numerous references therein for more detailed discussion. Verification is defined as an analysis of the quantitative correspondence between a conceptual model and its numerical implementation. Verification is exercised primarily in the computational domain and may be viewed as a modern descendant of classic numerical analysis. This term is not to be confused with validation, which is defined as an analysis of the quantitative correspondence between a numerical simulation and the desired quantities of interest in a physical experiment. Here critical attention must be paid to analysis and quantification of systemic errors introduced by selection of a specific model and the associated reductions and simplifications in the physics that the model represents in comparison with the referent physical process. Colloquially speaking, it is here that one attempts to quantify the ‘‘unknown unknowns.’’ In general, it is very difficult to quantify such errors. An important area of research in validation is to assess how confidence in the prediction of a model degrades while interpolating between or extrapolating from conditions where *This work is a contribution of the National Institute of Standards and Technology and is not subject to copyright in the United States. JOM, Vol. 66, No. 7, 2014

Ethnogenesis and Ethnic Processes in Modern Kazakhstan

Finding the roots of ethnic Kazakh people is extremely complex, and is intimately connected with the study of ancient Kazakhstan and adjacent areas of Eurasia. Among the many aspects of the origin of the Kazakh people are two aspects: linguistic and anthropological. There is every reason to believe that the two processes in the area under parallel development, mainly for historical vertical. This approach allows us to trace the continuity and preserve the “ancestral” traits. However, in certain periods of history played a role and the development of the horizontal line. It is noteworthy that in the ancient indigenous monks region had a common linguistic and anthropological basis, and modern descendants of the genetic clustering generally corresponds to the linguistic. Kazakhstan's long history can be divided into two periods: the Indo-European and Turkic. The first period, in spite of their considerable time distance, appears as a real phase formed not only with strong economic and cultural traditions, but also a number of prominent ethnic groups. This article is an analysis of the ethnic processes in Kazakhstan.

Pastoral counter-conducts: Religious resistance in Foucault’s genealogy of Christianity

The internal resistance to religious forms of power is often at issue in Michel Foucault’s genealogy of Christianity. For this anti-clerical Nietzschean, religion is, like science, always a battle over bodies and souls. In his 1978 Collège de France lectures, he traced the nature and descent of an apparatus of “pastoral power” characterized by confession, direction, obedience, and sacrifice. Governmental rationality, both individualizing and totalizing, is its modern descendant. At different moments, Foucault rather infamously opposed to the pastorate and governmentality such ethico-political spiritualities as the Iranian Revolution and ancient Greek ascesis, but he also took care to identify numerous forms of resistance specific and internal to Christianity itself. His lecture of 1 March 1978 outlined five examples of “insurrections of conduct”: “eschatology, Scripture, mysticism, the community, and ascesis.” I will detail Foucault’s analysis of pastoral counter-conducts, and explore how he sets up the nature and stakes of this tension within Christianity and its secular kin.

Paleoenvironmental conditions for the development of calcareous nannofossil acme during the late Miocene in the eastern equatorial Pacific

Repeated monospecific coccolithophore dominance intervals (acmes) of specimens belonging to the Noelaerhabdaceae family—including the genus Reticulofenestra and modern descendants Emiliania and Gephyrocapsa—occurred during the Neogene. Such acme was recognized during the late Miocene (~ 8.6 Ma), at a time of a major reorganization of nannofossil assemblages resulting in a worldwide temporary disappearance of larger forms of the genus Reticulofenestra (R. pseudoumbilicus) and the gradual recovery and dominance of its smaller forms (< 5 µm). In this study we present a multiproxy investigation of late Miocene sediments from the east equatorial Pacific Integrated Ocean Drilling Program Site U1338 where small reticulofenestrid-type placoliths with a closed central area—known as small Dictyococcites spp. (< 3 µm)—formed an acme. We report on oxygen and carbon stable isotope records of multispecies planktic calcite and alkenone-derived sea surface temperature. Our data indicate that, during this 100 kyr long acme, the east equatorial Pacific thermocline remained deep and stable. Local surface stratification state fails to explain this acme and thus contradicts the model-based hypothesis of a Southern Ocean high-latitude nutrient control of the surface waters in the east equatorial Pacific. Instead, our findings suggest that external forcing such as an extended period of low eccentricity may have created favorable conditions for the small Dictyococcites spp. growth.

No Evidence from Genome-wide Data of a Khazar Origin for the Ashkenazi Jews

The origin and history of the Ashkenazi Jewish population have long been of great interest, and advances in high-throughput genetic analysis have recently provided a new approach for investigating these topics. We and others have argued on the basis of genome-wide data that the Ashkenazi Jewish population derives its ancestry from a combination of sources tracing to both Europe and the Middle East. It has been claimed, however, through a reanalysis of some of our data, that a large part of the ancestry of the Ashkenazi population originates with the Khazars, a Turkic-speaking group that lived to the north of the Caucasus region ~1,000 years ago. Because the Khazar population has left no obvious modern descendants that could enable a clear test for a contribution to Ashkenazi Jewish ancestry, the Khazar hypothesis has been difficult to examine using genetics. Furthermore, because only limited genetic data have been available from the Caucasus region, and because these data have been concentrated in populations that are genetically close to populations from the Middle East, the attribution of any signal of Ashkenazi-Caucasus genetic similarity to Khazar ancestry rather than shared ancestral Middle Eastern ancestry has been problematic. Here, through integration of genotypes from newly collected samples with data from several of our past studies, we have assembled the largest data set available to date for assessment of Ashkenazi Jewish genetic origins. This data set contains genome-wide single-nucleotide polymorphisms in 1,774 samples from 106 Jewish and non-Jewish populations that span the possible regions of potential Ashkenazi ancestry: Europe, the Middle East, and the region historically associated with the Khazar Khaganate. The data set includes 261 samples from 15 populations from the Caucasus region and the region directly to its north, samples that have not previously been included alongside Ashkenazi Jewish samples in genomic studies. Employing a variety of standard techniques for the analysis of population-genetic structure, we found that Ashkenazi Jews share the greatest genetic ancestry with other Jewish populations and, among non-Jewish populations, with groups from Europe and the Middle East. No particular similarity of Ashkenazi Jews to populations from the Caucasus is evident, particularly populations that most closely represent the Khazar region. Thus, analysis of Ashkenazi Jews together with a large sample from the region of the Khazar Khaganate corroborates the earlier results that Ashkenazi Jews derive their ancestry primarily from populations of the Middle East and Europe, that they possess considerable shared ancestry with other Jewish populations, and that there is no indication of a significant genetic contribution either from within or from north of the Caucasus region.

No evidence from genome-wide data of a Khazar origin for the Ashkenazi Jews.

The origin and history of the Ashkenazi Jewish population have long been of great interest, and advances in high-throughput genetic analysis have recently provided a new approach for investigating these topics. We and others have argued on the basis of genome-wide data that the Ashkenazi Jewish population derives its ancestry from a combination of sources tracing to both Europe and the Middle East. It has been claimed, however, through a reanalysis of some of our data, that a large part of the ancestry of the Ashkenazi population originates with the Khazars, a Turkic-speaking group that lived to the north of the Caucasus region ~1,000 years ago. Because the Khazar population has left no obvious modern descendants that could enable a clear test for a contribution to Ashkenazi Jewish ancestry, the Khazar hypothesis has been difficult to examine using genetics. Furthermore, because only limited genetic data have been available from the Caucasus region, and because these data have been concentrated in populations that are genetically close to populations from the Middle East, the attribution of any signal of Ashkenazi-Caucasus genetic similarity to Khazar ancestry rather than shared ancestral Middle Eastern ancestry has been problematic. Here, through integration of genotypes from newly collected samples with data from several of our past studies, we have assembled the largest data set available to date for assessment of Ashkenazi Jewish genetic origins. This data set contains genome-wide single-nucleotide polymorphisms in 1,774 samples from 106 Jewish and non-Jewish populations that span the possible regions of potential Ashkenazi ancestry: Europe, the Middle East, and the region historically associated with the Khazar Khaganate. The data set includes 261 samples from 15 populations from the Caucasus region and the region directly to its north, samples that have not previously been included alongside Ashkenazi Jewish samples in genomic studies. Employing a variety of standard techniques for the analysis of population-genetic structure, we found that Ashkenazi Jews share the greatest genetic ancestry with other Jewish populations and, among non-Jewish populations, with groups from Europe and the Middle East. No particular similarity of Ashkenazi Jews to populations from the Caucasus is evident, particularly populations that most closely represent the Khazar region. Thus, analysis of Ashkenazi Jews together with a large sample from the region of the Khazar Khaganate corroborates the earlier results that Ashkenazi Jews derive their ancestry primarily from populations of the Middle East and Europe, that they possess considerable shared ancestry with other Jewish populations, and that there is no indication of a significant genetic contribution either from within or from north of the Caucasus region.

Reference genomes and transcriptomes of Nicotiana sylvestris and Nicotiana tomentosiformis

BackgroundNicotiana sylvestris and Nicotiana tomentosiformis are members of the Solanaceae family that includes tomato, potato, eggplant and pepper. These two Nicotiana species originate from South America and exhibit different alkaloid and diterpenoid production. N. sylvestris is cultivated largely as an ornamental plant and it has been used as a diploid model system for studies of terpenoid production, plastid engineering, and resistance to biotic and abiotic stress. N. sylvestris and N. tomentosiformis are considered to be modern descendants of the maternal and paternal donors that formed Nicotiana tabacum about 200,000 years ago through interspecific hybridization. Here we report the first genome-wide analysis of these two Nicotiana species.ResultsDraft genomes of N. sylvestris and N. tomentosiformis were assembled to 82.9% and 71.6% of their expected size respectively, with N50 sizes of about 80 kb. The repeat content was 72-75%, with a higher proportion of retrotransposons and copia-like long terminal repeats in N. tomentosiformis. The transcriptome assemblies showed that 44,000-53,000 transcripts were expressed in the roots, leaves or flowers. The key genes involved in terpenoid metabolism, alkaloid metabolism and heavy metal transport showed differential expression in the leaves, roots and flowers of N. sylvestris and N. tomentosiformis.ConclusionsThe reference genomes of N. sylvestris and N. tomentosiformis represent a significant contribution to the SOL100 initiative because, as members of the Nicotiana genus of Solanaceae, they strengthen the value of the already existing resources by providing additional comparative information, thereby helping to improve our understanding of plant metabolism and evolution.

Bringing Ancient Proteins To Life

Ancient proteins differed from their modern descendants in sequence and, sometimes, function. Scientists would like to know how those proteins actually worked. Unfortunately, they disappeared with the organisms that used them, and scientists can’t time travel to study them. Or can they? When it comes to studying ancient proteins, scientists have their own version of time travel. By comparing the sequences of closely related modern proteins, scientists can deduce the sequence that appeared in their common ancestors. They can then synthesize those ancestral proteins in the lab, using either bacteria or in vitro systems to resurrect them. Scientists use those resurrected proteins in multiple ways. Evolutionary biologists use them to understand evolutionary history and how proteins acquire new functions. Protein engineers use them as starting points for designing proteins with new functions. By using the sequences of closely related proteins from multiple species, scientists can build a so-called phylogenetic...

The poverty of Boldizzoni: Resurrecting the German Historical School

Boldizzoni's attack on cliometrics is unpersuasive, in part because he does not grasp economics and its uses, in part because he admires uncritically the German Historical School and their modern descendants, the French Annalistes. Much is to be learned from the earlier schools, but not by throwing away the insights that economics gives into how an economy holds together.

No Evidence from Genome-wide Data of a Khazar Origin fo the Ashkenazi Jews

The origin and history of the Ashkenazi Jewish population have long been of great interest, and advances in high-throughput genetic analysis have recently provided a new approach for investigating these topics. We and others have argued on the basis of genome-wide data that the Ashkenazi Jewish population derives its ancestry from a combination of sources tracing to both Europe and the Middle East. It has been claimed, however, through a reanalysis of some of our data, that a large part of the ancestry of the Ashkenazi population originates with the Khazars, a Turkic-speaking group that lived to the north of the Caucasus region ~1,000 years ago. Because the Khazar population has left no obvious modern descendants that could enable a clear test for a contribution to Ashkenazi Jewish ancestry, the Khazar hypothesis has been difficult to examine using genetics. Furthermore, because only limited genetic data have been available from the Caucasus region, and because these data have been concentrated in populations that are genetically close to populations from the Middle East, the attribution of any signal of Ashkenazi-Caucasus genetic similarity to Khazar ancestry rather than shared ancestral Middle Eastern ancestry has been problematic. Here, through integration of genotypes from newly collected samples with data from several of our past studies, we have assembled the largest data set available to date for assessment of Ashkenazi Jewish genetic origins. This data set contains genome-wide single-nucleotide polymorphisms in 1,774 samples from 106 Jewish and non-Jewish populations that span the possible regions of potential Ashkenazi ancestry: Europe, the Middle East, and the region historically associated with the Khazar Khaganate. The data set includes 261 samples from 15 populations from the Caucasus region and the region directly to its north, samples that have not previously been included alongside Ashkenazi Jewish samples in genomic studies. Employing a variety of standard techniques for the analysis of population-genetic structure, we found that Ashkenazi Jews share the greatest genetic ancestry with other Jewish populations and, among non-Jewish populations, with groups from Europe and the Middle East. No particular similarity of Ashkenazi Jews to populations from the Caucasus is evident, particularly populations that most closely represent the Khazar region. Thus, analysis of Ashkenazi Jews together with a large sample from the region of the Khazar Khaganate corroborates the earlier results that Ashkenazi Jews derive their ancestry primarily from populations of the Middle East and Europe, that they possess considerable shared ancestry with other Jewish populations, and that there is no indication of a significant genetic contribution either from within or from north of the Caucasus region.

Origin and diversity of the words denoting some traditional Eurasian pulse crops in Mongolic and Tungusic

Abstract Supporters of the existence of the Altaic language family consider it to include Turkic, Mongolic, Tungusic, Korean and Japonic branches, and believe that all of these originated from the Proto-Altaic. On the basis of archaeological findings, one may expect that traditional Eurasian pulse crops, such as peas (Pisum sativum), lentils (Lens culinaris), chickpeas (Cicer arietinum), faba beans (Vicia faba), vetchlings (Lathyrus spp.) and vetches (Vicia spp.), were known to the ancestors of the modern Altaic nations. This assumption is confirmed by two Proto- Altaic roots. The first root is *bŭkrV, denoting pea. Its three main direct derivatives preserved the original meaning and transferred it to their modern descendants, namely the Proto-Turkic *burčak to the majority of modern Turkic languages, such as Kazakh with burşaq; the Proto-Mongolic *buγurčag, giving the modern Mongolian būrcag; and the Proto-Tungusic *boKa-ri, giving the Manchu boxori. Another root is *zịăbsa, denoting lentil. It gave the Proto-Turkic *jasimuk, the Proto-Mongolic *sisi and the Proto-Tungusic *sibsV. In Turkic and Tungusic, its original meaning was preserved, such as in the Turkmen jasmiq or the Nanai siusi, while in Mongolic it shifted to Sorghum spp., such as in Kalmyk, with šiš.

Darwinian behavior in a cold, sporadically fed pool of ribonucleotides.

A testable, explicit origin for Darwinian behavior, feasible on a chaotic early Earth, would aid origins discussion. Here I show that a pool receiving unreliable supplies of unstable ribonucleotide precursors can recurrently fill this role. By using numerical integration, the differential equations governing a sporadically fed pool are solved, yielding quantitative constraints for the proliferation of molecules that also have a chemical phenotype. For example, templated triphosphate nucleotide joining is >10(4) too slow, suggesting that a group more reactive than pyrophosphate activated primordial nucleotides. However, measured literature rates are sufficient if the Initial Darwinian Ancestor (IDA) resembles a 5'-5' cofactor-like dinucleotide RNA, synthesized via activation with a phosphorimidazolide-like group. A sporadically fed pool offers unforeseen advantages; for example, the pool hosts a novel replicator which is predominantly unpaired, even though it replicates. Such free template is optimized for effective selection during its replication. Pool nucleotides are also subject to a broadly based selection that impels the population toward replication, effective selection, and Darwinian behavior. Such a primordial pool may have left detectable modern traces. A sporadically fed ribonucleotide pool also fits a recognizable early Earth environment, has recognizable modern descendants, and suits the early shape of the phylogenetic tree of Earthly life. Finally, analysis points to particular data now needed to refine the hypothesis. Accordingly, a kinetically explicit chemical hypothesis for a terran IDA can be justified, and informative experiments seem readily accessible.

Conservation of the Folding Mechanism between Designed Primordial (βα)8-Barrel Proteins and Their Modern Descendant

The (βα)(8)-barrel is among the most ancient, frequent, and versatile enzyme structures. It was proposed that modern (βα)(8)-barrel proteins have evolved from an ancestral (βα)(4)-half-barrel by gene duplication and fusion. We explored whether the mechanism of protein folding has remained conserved during this long-lasting evolutionary process. For this purpose, potential primordial (βα)(8)-barrel proteins were constructed by the duplication of a (βα)(4) element of a modern (βα)(8)-barrel protein, imidazole glycerol phosphate synthase (HisF), followed by the optimization of the initial construct. The symmetric variant Sym1 was less stable than HisF and its crystal structure showed disorder in the contact regions between the half-barrels. The next generation variant Sym2 was more stable than HisF, and the contact regions were well resolved. Remarkably, both artificial (βα)(8)-barrels show the same refolding mechanism as HisF and other modern (βα)(8)-barrel proteins. Early in folding, they all equilibrate rapidly with an off-pathway species. On the productive folding path, they form closely related intermediates and reach the folded state with almost identical rates. The high energy barrier that synchronizes folding is thus conserved. The strong differences in stability between these proteins develop only after this barrier and lead to major changes in the unfolding rates. We conclude that the refolding mechanism of (βα)(8)-barrel proteins is robust. It evolved early and, apparently, has remained conserved upon the diversification of sequences and functions that have taken place within this large protein family.

The UlaG protein family defines novel structural and functional motifs grafted on an ancient RNase fold

BackgroundBacterial populations are highly successful at colonizing new habitats and adapting to changing environmental conditions, partly due to their capacity to evolve novel virulence and metabolic pathways in response to stress conditions and to shuffle them by horizontal gene transfer (HGT). A common theme in the evolution of new functions consists of gene duplication followed by functional divergence. UlaG, a unique manganese-dependent metallo-β-lactamase (MBL) enzyme involved in L-ascorbate metabolism by commensal and symbiotic enterobacteria, provides a model for the study of the emergence of new catalytic activities from the modification of an ancient fold. Furthermore, UlaG is the founding member of the so-called UlaG-like (UlaGL) protein family, a recently established and poorly characterized family comprising divalent (and perhaps trivalent) metal-binding MBLs that catalyze transformations on phosphorylated sugars and nucleotides.ResultsHere we combined protein structure-guided and sequence-only molecular phylogenetic analyses to dissect the molecular evolution of UlaG and to study its phylogenomic distribution, its relatedness with present-day UlaGL protein sequences and functional conservation. Phylogenetic analyses indicate that UlaGL sequences are present in Bacteria and Archaea, with bona fide orthologs found mainly in mammalian and plant-associated Gram-negative and Gram-positive bacteria. The incongruence between the UlaGL tree and known species trees indicates exchange by HGT and suggests that the UlaGL-encoding genes provided a growth advantage under changing conditions. Our search for more distantly related protein sequences aided by structural homology has uncovered that UlaGL sequences have a common evolutionary origin with present-day RNA processing and metabolizing MBL enzymes widespread in Bacteria, Archaea, and Eukarya. This observation suggests an ancient origin for the UlaGL family within the broader trunk of the MBL superfamily by duplication, neofunctionalization and fixation.ConclusionsOur results suggest that the forerunner of UlaG was present as an RNA metabolizing enzyme in the last common ancestor, and that the modern descendants of that ancestral gene have a wide phylogenetic distribution and functional roles. We propose that the UlaGL family evolved new metabolic roles among bacterial and possibly archeal phyla in the setting of a close association with metazoans, such as in the mammalian gastrointestinal tract or in animal and plant pathogens, as well as in environmental settings. Accordingly, the major evolutionary forces shaping the UlaGL family include vertical inheritance and lineage-specific duplication and acquisition of novel metabolic functions, followed by HGT and numerous lineage-specific gene loss events.

The first Eocardiidae (Rodentia) in the Colhuehuapian (early Miocene) of Bryn Gwyn (northern Chubut, Argentina) and the early evolution of the peculiar cavioid rodents

ABSTRACT Caviidae and Hydrochoeridae (extant Cavioidea s.s.), probably the most peculiar among rodents, are characterized by their evergrowing double-heart-shaped cheekteeth. They have classically been rooted in Eocardiidae, which ranges from Deseadan to ‘Colloncuran’ (late Oligocene–middle Miocene) in Patagonia, although in the Deseadan and Colhuehuapian (early Miocene) remains are very scanty. For the Colhuehuapian, only one species coming from the southern cliff of the Colhué Huapi Lake (Gran Barranca, Chubut, Argentina) was known so far. In this paper, the first Colhuehuapian eocardiids from outside Gran Barranca are reported: Luantus minor, sp. nov., and Chubutomys leucoreios, sp. nov. They are represented by two fragmentary mandibles and a few isolated cheek teeth, from the Trelew Member of the Sarmiento Formation at Bryn Gwyn, lower valley of the Chubut River, Chubut. The new species enlarge the knowledge of eocardiid diversity, and reinforce the hypothesis of a basal dichotomy for the group. L. minor represents one of the smallest species of the series Asteromys + Luantus + Phanomys + Eocardia, which likely gave rise to modern Cavioidea s.s. C. leucoreios pertains to a group of species with precocious hypsodonty and apparently low diversity, but without modern descendant.

Urban Void and the Deconstruction of Neo-Platonic City-Form

Urban void sometimes amplifies alienation within urban space, and thus leads the way to the human craving for authenticity. Juxtaposing urban void with the conventional notion of urban objects, furthermore, conforms to Nietzsche's distinction between Dionysian and Apollonian deportment. The Apollonian is at the founding of the Platonic myth of the Ideal City and its modern descendant, the myth of the Rational City. Modern urban planning has been object-directed and, consistent with the historical trend since the Renaissance, has become a constituent of a Neo-Platonic mythology that insists on forging a city as an urban technological artifact. Most existing urban parks and squares, as well as suburban gardens, within this approach, only augment the subordinate standing of urban voids. Yet the significance of urban void, as the unplanned place that represents the pre-rational, the genuine and the unadulterated, ought to lead to its re-introduction into city-form as a conduit for self-reflection and authenticity. Recognizing urban void for its significance may reintroduce an important Dionysian feature into city-form, leading to deliberate carving of authentic urban spaces.