Insuperable problems of the genetic code initially emerging in an RNA world.
ABSTRACT: Differential equations for error-prone information transfer (template replication, transcription or translation) are developed in order to consider, within the theory of autocatalysis, the advent of coded protein synthesis. Variations of these equations furnish a basis for comparing the plausibility of contrasting scenarios for the emergence of specific tRNA aminoacylation, ultimately by enzymes, and the relationship of this process with the origin of the universal system of molecular biological information processing embodied in the Central Dogma. The hypothetical RNA World does not furnish an adequate basis for explaining how this system came into being, but principles of self-organisation that transcend Darwinian natural selection furnish an unexpectedly robust basis for a rapid, concerted transition to genetic coding from a peptide·RNA world.
Project description:Genetic coding is generally thought to have required ribozymes whose functions were taken over by polypeptide aminoacyl-tRNA synthetases (aaRS). Two discoveries about aaRS and their interactions with tRNA substrates now furnish a unifying rationale for the opposite conclusion: that the key processes of the Central Dogma of molecular biology emerged simultaneously and naturally from simple origins in a peptide•RNA partnership, eliminating the epistemological utility of a prior RNA world. First, the two aaRS classes likely arose from opposite strands of the same ancestral gene, implying a simple genetic alphabet. The resulting inversion symmetries in aaRS structural biology would have stabilized the initial and subsequent differentiation of coding specificities, rapidly promoting diversity in the proteome. Second, amino acid physical chemistry maps onto tRNA identity elements, establishing reflexive, nanoenvironmental sensing in protein aaRS. Bootstrapping of increasingly detailed coding is thus intrinsic to polypeptide aaRS, but impossible in an RNA world. These notions underline the following concepts that contradict gradual replacement of ribozymal aaRS by polypeptide aaRS: 1) aaRS enzymes must be interdependent; 2) reflexivity intrinsic to polypeptide aaRS production dynamics promotes bootstrapping; 3) takeover of RNA-catalyzed aminoacylation by enzymes will necessarily degrade specificity; and 4) the Central Dogma's emergence is most probable when replication and translation error rates remain comparable. These characteristics are necessary and sufficient for the essentially de novo emergence of a coupled gene-replicase-translatase system of genetic coding that would have continuously preserved the functional meaning of genetically encoded protein genes whose phylogenetic relationships match those observed today.
Project description:Kinetic modeling using nonlinear differential equations is proposed to analyze the spontaneous generation of enantiomeric excess in the autocatalytic addition of diisopropylzinc to prochiral pyrimidine carbaldehydes (Soai reaction). Our approach reproduces experimentally observed giant chiral amplification from an initial enantiomeric excess of <10(-6)% to >60%, high sensitivity and positive response to the presence of minute amounts of chiral initiator at concentrations <10(-14) M, and spontaneous absolute asymmetric synthesis from achiral starting conditions. From our numerical simulations using kinetic schemes derived from the Frank model, including stereospecific autocatalysis and mutual inhibition, we have shown that it is possible to reproduce the mirror-symmetry-breaking behavior of the Soai reaction under batch conditions leading to a bimodal enantiomeric product distribution. Mirror-symmetry breaking was found to be resistant to a loss of stereoselectivity up to 30%. While the mutual inhibition between enantiomers seems to originate from the presence of dimerization equilibria, the exact nature of the autocatalytic stereoselective process still remains to be revealed. From the kinetic viewpoint, simple autocatalysis involving monomers as the catalytic species is consistent with all reported experimental effects of the Soai reaction.
Project description:The discovery of ribozymes led to the proposal of an RNA world, where a single type of molecule was supposedly capable of self-replication and chemical catalysis. We show here that both autocatalysis and organocatalysis can be engineered into a synthetic structure. The compound is shown to selectively accelerate its own formation and catalyze either hydrogenation or nucleophilic addition to alpha,beta-unsaturated aldehydes. The observed reactivity indicates that the components of a purported pre-RNA world conceivably include smaller organic molecules.
Project description:Chemical reactions make cells work only if the participating chemicals are delivered to desired locations in a timely and precise fashion. Most research to date has focused on active-transport mechanisms, although passive diffusion is often equally rapid and energetically less costly. Capitalizing on these advantages, cells have developed sophisticated reaction-diffusion (RD) systems that control a wide range of cellular functions-from chemotaxis and cell division, through signaling cascades and oscillations, to cell motility. These apparently diverse systems share many common features and are "wired" according to "generic" motifs such as nonlinear kinetics, autocatalysis, and feedback loops. Understanding the operation of these complex (bio)chemical systems requires the analysis of pertinent transport-kinetic equations or, at least on a qualitative level, of the characteristic times of the constituent subprocesses. Therefore, in reviewing the manifestations of cellular RD, we also describe basic theory of reaction-diffusion phenomena.
Project description:The evolutionary processes that drive rapid species diversification are poorly understood. In particular, it is unclear whether Darwinian adaptation or non-adaptive processes are the primary drivers of explosive species diversifications. Here we show that repeated rapid radiations within New World lupins (Lupinus, Leguminosae) were underpinned by a major increase in the frequency of adaptation acting on coding and regulatory changes genome-wide. This contrasts with far less frequent adaptation in genomes of slowly diversifying lupins and all other plant genera analysed. Furthermore, widespread shifts in optimal gene expression coincided with shifts to high rates of diversification and evolution of perenniality, a putative key adaptation trait thought to have triggered the evolutionary radiations in New World lupins. Our results reconcile long-standing debate about the relative importance of protein-coding and regulatory evolution, and represent the first unambiguous evidence for the rapid onset of lineage- and genome-wide accelerated Darwinian evolution during rapid species diversification.
Project description:To satisfy the minimal requirements for life, an information carrying molecular structure must be able to convert resources into building blocks and also be able to adapt to or modify its environment to enhance its own proliferation. Furthermore, new copies of itself must have variable fitness such that evolution is possible. In practical terms, a minimal protocell should be characterized by a strong coupling between its metabolism and genetic subsystem, which is made possible by the container. There is still no general agreement on how such a complex system might have been naturally selected for in a prebiotic environment. However, the historical details are not important for our investigations as they are related to assembling and evolution of protocells in the laboratory. Here, we study three different minimal protocell models of increasing complexity, all of them incorporating the coupling between a 'genetic template', a container and, eventually, a toy metabolism. We show that for any local growth law associated with template self-replication, the overall temporal evolution of all protocell's components follows an exponential growth (efficient or uninhibited autocatalysis). Thus, such a system attains exponential growth through coordinated catalytic growth of its component subsystems, independent of the replication efficiency of the involved subsystems. As exponential growth implies the survival of the fittest in a competitive environment, these results suggest that protocell assemblies could be efficient vehicles in terms of evolving through Darwinian selection.
Project description:BACKGROUND: Ionizing-radiation-resistant bacteria (IRRB) show a surprising capacity for adaptation to ionizing radiation and desiccation. Positive Darwinian selection is expected to play an important role in this trait, but no data are currently available regarding the role of positive adaptive selection in resistance to ionizing-radiation and tolerance of desiccation. We analyzed the four known genome sequences of IRRB (Deinococcus geothermalis, Deinococcus radiodurans, Kineococcus radiotolerans, and Rubrobacter xylanophilus) to determine the role of positive Darwinian selection in the evolution of resistance to ionizing radiation and tolerance of desiccation. RESULTS: We used the programs MultiParanoid and DnaSP to deduce the sets of orthologs that potentially evolved due to positive Darwinian selection in IRRB. We find that positive selection targets 689 ortholog sets of IRRB. Among these, 58 ortholog sets are absent in ionizing-radiation-sensitive bacteria (IRSB: Escherichia coli and Thermus thermophilus). The most striking finding is that all basal DNA repair genes in IRRB, unlike many of their orthologs in IRSB, are subject to positive selection. CONCLUSION: Our results provide the first in silico prediction of positively selected genes with potential roles in the molecular basis of resistance to gamma-radiation and tolerance of desiccation in IRRB. Identification of these genes provides a basis for future experimental work aimed at understanding the metabolic networks in which they participate.
Project description:Phlebotomine sandflies of the genus Sergentomyia are widely distributed throughout the Old World. It has been suggested that Sergentomyia spp are involved in the transmission of Leishmania in India and Africa, whereas Phlebotomus spp are thought to be the sole vectors of Leishmania in the Old World. In this study, Leishmania major DNA was detected in one Sergentomyia minuta specimen that was collected in the southern region of Portugal. This study challenges the dogma that Leishmania is exclusively transmitted by species of the genus Phlebotomus in the Old World.
Project description:Diisopropylzinc alkylation of pyrimidine aldehydes-the Soai reaction, with its astonishing attribute of amplifying asymmetric autocatalysis-occupies a unique position in organic chemistry and stands as an eminent challenge for mechanistic elucidation. A new paradigm of "mixed catalyst-substrate" experiments with pyrimidine and pyridine systems allows a disconnection of catalysis from autocatalysis, providing insights into the role played by reactant and alkoxide structure. The alkynyl substituent favorably tunes catalyst solubility, aggregation, and conformation while modulating substrate reactivity and selectivity. The alkyl groups and the heteroaromatic core play further complementary roles in catalyst aggregation and substrate binding. In the study of these structure-activity relationships, novel pyridine substrates demonstrating amplifying autocatalysis were identified. Comparison of three autocatalytic systems representing a continuum of nitrogen Lewis basicity strength suggests how the strength of N-Zn binding events is a predominant contributor toward the rate of autocatalytic progression.
Project description:Super-hydrophobic, super-oleo(amphi)phobic, and super-omniphobic materials are universally important in the fields of science and engineering. Despite rapid advancements, gaps of understanding still exist between each distinctive wetting state. The transition of super-hydrophobicity to super-(oleo-, amphi-, and omni-)phobicity typically requires the use of re-entrant features. Today, re-entrant geometry induced super-(amphi- and omni-)phobicity is well-supported by both experiments and theory. However, owing to geometrical complexities, the concept of re-entrant geometry forms a dogma that limits the industrial progress of these unique states of wettability. Moreover, a key fundamental question remains unanswered: are extreme surface chemistry enhancements able to influence super-liquid repellency? Here, this was rigorously tested via an alternative pathway that does not require explicit designer re-entrant features. Highly controllable and tunable vertical network polymerization and functionalization were used to achieve fluoroalkyl densification on nanoparticles. For the first time, relative fluoro-functionalization densities are quantitatively tuned and correlated to super-liquid repellency performance. Step-wise tunable super-amphiphobic nanoparticle films with a Cassie-Baxter state (contact angle of >150° and sliding angle of <10°) against various liquids is demonstrated. This was tested down to very low surface tension liquids to a minimum of ca. 23.8 mN/m. Such findings could eventually lead to the future development of super-(amphi)omniphobic materials that transcend the sole use of re-entrant geometry.