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origins13 Participant Title Abstract Steven Benner Chemical Paradoxes in Origins and Possible Geological Solutions Four paradoxes obstruct current efforts to understand how life originated on Earth: (a) The Tar Paradox. Organic molecules, given energy and left to themselves, devolve into complex mixtures, “asphalts” better suited for paving roads than supporting Darwinian evolution. Any scenario for origins requires a way to allow organic material to escape this devolution into a state that has Darwinian behavior, enabling replication with imperfections, where the imperfections are themselves replicatable. (b) The Water Paradox: Water is commonly viewed as essential for life. So are biopolymers, like RNA, DNA, and proteins. However, contemporary terran biopolymers are corroded by water. Any scenario for origins must manage the apparent contractiction where life needs a substance (water) this is inherently toxic to life. (c) The Single Biopolymer Paradox. Even if we can make biopolymers prebioically, it is hard to imaging making two or three (DNA, RNA, proteins) at the same time. This drives the search for a single biopolymer that "does" both genetics and catalysis. However, genetics places very different demands on the behavior of a biopolymer than catalysis. Catalytic biopolymers should fold; genetic biopolymers should not fold. Catalytic biopolymers should contain many building blocks; genetic biopolymers should contain few. Any "biopolymer first" model for origins must resolve this paradox. (d) The Probability Paradox. Some biopolymers, like RNA, strike a reasonable compromise between the needs of genetics and of catalysis. However, experiments show that RNA that destroys RNA is more likely to be found in a pool of RNA sequences than RNA that makes RNA. This talk will review experimental data that suggest early planetary environments and mineralogy that might avoid, mitigate, and possibly resolve these paradoxes. Key are the presence of minerals, including borates and molybdates, that interact with organic species that are intermediates between atmospheric carbon dioxide and dinitrogen and RNA. Productive interaction also requires a subaerial environment having only intermittent interaction with water. Recent data suggests that such environments might even be found today on Mars. Finally, we shall consider ways that synthetic biology might be able to address these issues, including approaches that construct artificial life forms as a step towards understanding the relation between chemical diversity in biological macromolecules and their functional behaviors. Edwin Bergin The origin of water in terrestrial worlds Tanja Bosak The Meaning of Stromatolites Dieter Braun Nonequilibrium First: Towards a thermally driven Darwin Process The origin of life is one of the fundamental, unsolved riddles of modern science. Life as we know it is a stunningly complex nonequilibrium process, keeping its entropy low against the second law of thermo-dynamics. Therefore it is straightforward to argue that first living systems had to start in a natural non-equilibrium settings. Recent experiments with non-equilibrium microsystems suggest that geological conditions should be able to drive molecular evolution, i.e. the combined replication and selection of genetic molecules towards ever increasing complexity. As a start, we explored the non-equilibrium setting of natural thermal gradients. Temperature differences across rock fissures accumulate small monomers more than millionfold [1] by thermo-phoresis and convection [2]. Longer molecules are exponentially better accumulated, hyperexponentially shifting the polymerization equilibrium towards long RNA strands [3]. The same setting implements convective temperature oscillations which overcome template poisoning and yield length-insensitive, exponential replication kinetics [4]. Accumulation and thermally driven replication was demonstrated in the same chamber, driven by the same temperature gradient [5]. Protein-free, non-ligating replication schemes can be driven by thermal convection. For example, the hairpins of tRNA can be used for reversible codon-sequence replication, bridging from replication of genes to the translation of proteins [6]. Non-templated polymerization and hybridization-dependent degradation leads to replication-like information transmission [7]. Replication and trapping of DNA persist over long time in a constant influx of monomers, closely approaching the criteria for an autonomous Darwin process. Experiments using non-equilibrium conditions at the microscale are non-trivial. For example, molecules have to be detected selectively with the most sensitive biochemical, optical and microfluidic approaches. Advances of biotechnology in this regime is very fruitful. Our award winning NanoTemper spinoff company [8] demonstrated that basic research for the origin of life can lead to cutting edge biotechnology [8][9]. Besides temperature gradients, many more non-equilibrium settings can be imagined and become increasingly accessible to experimentation. For example, geological pH gradients, geological redox potentials or the optical excitation of geological nanoparticles should drive metabolic reactions in a very peculiar way. To be successful, an effort on the origin of life has to be embedded in a strong and very active inter-dis-cip-linary background of biology, biochemistry, chemistry, astrogeology and not the least, theoretical modeling at various levels of abstraction. [1] PNAS 104, 9346–9351 (2007) [2] PNAS 103, 19678–19682 (2006) [3] PNAS.1303222110 (2013) [4] PRL 91, 158103 (2003) [5] PRL 104, 188102 (2010) [6] PRL 108, 238104 (2012) [7] PRL 107, 018101 (2011) [8] Nature Communications, 1, 100 (2010) [9] PNAS, 106, 21649–21654 (2009) John Chaput On the Origin of Biomolecular Function: From Artificial Genetic Polymers to Novel Protein Folds Abstract. Life presumably arose through a series of discrete steps in which molecular systems gave rise to unicellular organisms with DNA genomes and protein enzymes. As we study the path from chemistry to biology, several interesting scientific questions arise that are worthy of experimental investigation. One question that has captured our attention concerns the origin of our genetic material. According to the RNA world hypothesis, earlier life forms were composed of RNA molecules that stored genetic information and catalyzed chemical reactions. Although the chemical plausibility of the RNA world remains strong, it is not clear that RNA was the first genetic material. One could imagine that whatever chemistry gave rise to RNA-based life would have produced other RNA analogues, some of which could have preceded or competed directly with RNA. Threose nucleic acid (or TNA), an alternative genetic polymer in which the natural ribose sugar found in RNA has been replaced with an unnatural threose sugar, has received considerable attention as a possible RNA progenitor. Threose is chemically simpler than ribose and TNA polymers are able to exchange genetic information with themselves and with other strands of RNA. However, to establish a primordial metabolism, TNA would also need to fold itself into shapes that can catalyze important chemical reactions. To explore this possibility, we have developed a Darwinian evolution system that makes it possible to evolve functional TNA molecules in response to external stimuli. In this talk, I will discuss our recent progress on TNA replication and provide evidence to support the role of TNA as a primordial genetic material. A second question that has attracted our attention concerns the origin and early evolution of functional proteins. Therefore, a portion of my talk will examine the evolution of functional proteins from pools of random sequences. Irene Chen Evolution during early life in the RNA World The origin of life is believed to have progressed through an RNA World, in which RNA acted as both genetic material and functional molecules. Understanding early evolution requires systematic knowledge of the relationship between RNA sequence and functional activity. In particular, knowing the structure of the fitness landscape of RNA is critical to estimating the probability of the emergence of functional sequences and the role of historical accident during evolution. Much theoretical work has been devoted to fitness landscapes, but experimental maps have been relatively limited. We use in vitro selection on a pool of short RNA sequences that nearly saturates sequence space to reconstruct the form of a comprehensive fitness landscape. We also study mutations during non-enzymatic polymerization to understand how early RNA replicators would 'move' in sequence space. Ralf Conrad no talk Peter Coveney Theory, Modelling and Simulation of Origins of Life Processes In this talk we consider the contributions made by theory, modelling and simulation to fundamental issues in the origins of life. Theoretical approaches have had and continue to make major impact on the ''systems chemistry'' level, based on the analysis of the properties of nonlinear catalytic chemical reaction networks, which arise due to the auto-catalytic and cross-catalytic nature of many of the processes associated with self-replication and self-reproduction. We consider inter alia nonlinear kinetic models of RNA replication within a primordial Darwinian soup, the origins of homochirality and homochiral polymerization. We also discuss approaches to the numerical estimation of the rate parameters required as part of such models. Finally, we take a look at computationally-based molecular modelling techniques that are currently being deployed to investigate various scenarios relevant to the origins of life. Georg Feulner The evolution of Earth's atmosphere and climate through geological time Long-term changes of Earth's atmosphere and climate are governed by physical and chemical interactions with the crust and the biosphere. Powerful agents like plate tectonics and changes due to biological evolution have shaped Earth's climate history. In my presentation I will review the evolution of the atmosphere and the climate since the formation of Earth, highlighting the processes responsible for both gradual and drastic changes in the history of our planet, and the close interplay between the solid Earth, life and climate. Ulrich Gerland Nonequilibrium effects that facilitate the emergence of self-replication and evolution Christian Hallmann Fossil sedimentary lipids and the early evolution of life on Earth Thomas Henning Convener Kai-Uwe Hinrichs The Subseafloor Biosphere and the Limits of Life later, not fully decided on content of talk Birte Höcker On the origin of complex proteins Proteins are the molecular machines of the cell. They fold into specific three-dimensional structures to fulfill their functions. Similarities in protein sequence and structure suggest that the diverse set of modern proteins evolved from simpler and less specialized subunits. The most common subunit is the protein domain, which refers to a segment of the polypeptide chain that is able to fold autonomously and can be found in diverse protein architectures. Recombination of protein domains has led to the development of large multi-domain proteins, whose domains evolved to interact and accomplish one or more functions together. Similarly, domains themselves are hypothesized to originate from smaller subunits. Structural alignments between divergent pairs of protein domains suggest that nature assembled these fragments to create the structural diversity we observe today. To better understand the evolutionary mechanisms that generated this structural diversity, we applied the concepts of combinatorial assembly and fragment recruitment to construct new well-folded protein domains. We combined stable fragments from different topologies that are populated by thousands of proteins in all kingdoms of life to build new functional proteins, thereby demonstrating how new proteins can quickly develop and be competitive in today’s protein world. In addition to the synthetic biology approach that teaches us about possible evolutionary engineering pathways, we further elucidate natural relationships between protein domains. We started by comparing the sequences of two ancient super-folds to find the most closely related homologous groups between these two topologies. Further detailed analysis revealed a family of protein sequences that is intermediate to homologous groups representing different super-folds. The determination of the first representative crystal structure of one of its members supports the relationship and enables the development of a model explaining the evolutionary link. Overall, it becomes apparent that the systematic approach for the detection of intermediate steps between known protein folds enables us to cover missing areas of the protein universe and identify their origin. Additionally, further forays into uncharted protein structure territory will help us to better understand how sequence defines structure and, thus, ultimately unravel the protein folding problem. Lisa Kaltenegger Modeling observables of terrestrial exoplanet atmospheres - Super-Earths and Life A decade of exoplanet search has led to surprising discoveries, from hot giant planets orbiting their star within a few days, to planets orbiting two Suns, extremely hot, rocky worlds with potentially permanent lava on their surfaces due to the star's proximity all the way to the first potential rocky worlds in the Habitable Zone of their stars. Observation techniques have now reached the sensitivity to explore the chemical composition of the atmospheres as well as physical structure of some detected planets and find planets of less than 10 Earth masses (so called Super-Earths), among them some that may potentially be habitable. A 'modern' Earth system has existed for about 500 million years, but this period covers only ~15 % of Earth history. The foundation for a planet that is habitable by complex life has been laid during the preceding ~4 billion years. Ancient sediments hold clues to the nature of this early Earth system, but the absence of skeletonized animals and a paucity of microfossils in rocks of such age necessitate the use of sensitive chemical techniques. I will show how we can use the sedimentary hydrocarbon remnants of biological lipids to increase our understanding of the early evolution of life, gradually changing environmental conditions and the reciprocal interaction between both. Five confirmed planets orbit in the Habitable Zone of their host star. Observing mass and radius alone can not break the degeneracy of a planet’s nature due to the effect of an extended atmosphere that can also block the stellar light and increase the observed planetary radius significantly. Even if a unique solution would exist, planets with similar density, like Earth and Venus, present very different planetary environments in terms of habitable conditions. Therefore the question refocusses on atmospheric features to characterize a planetary environment. We will discuss observational features of rocky planets in the HZ of their stars that can be used to examine if our concept of habitability is correct, different geochemical cycles as well as signs of life through geological times. Using data as well as atmospheric models we will discuss how we can find the first habitable new worlds in the sky. Eugene Myers I would simply like to attend and listen I am a director at the MPI-CBG specializing in microscopy, image analysis, and DNA sequencing. Ann Pearson Molecular and Isotopic Signatures of Early Life (tba) Matthew Powner On the Divergent Origins of Functional RNA Recent progress towards understanding the chemical origins ribonucleotides will be discussed. Sascha P. Quanz Observational characterization of extrasolar planet atmospheres Steen Rasmussen Physicochemical and computational protocall assembly We sketch our main experimental- and computational results and highlight our recent results and challenges in coupling information, metabolism and container to form autonomous replicating protocells bottom up. Rebecca Schulman Robust information replication via crystal growth and scission Understanding how a simple chemical system can accurately replicate combinatorial information, such as a sequence, is an important question for both the study of life in the universe and for the development of evolutionary molecular design techniques. During biological sequence replication, a nucleic acid polymer serves as a template for the enzyme-catalyzed assembly of a complementary sequence. Enzymes then separate the template and complement before the next round of replication. Attempts to understand how replication could occur more simply, such as without enzymes, have largely focused on developing minimal versions of this replication process. Here we describe how a different mechanism, crystal growth and scission, can accurately replicate chemical sequences without enzymes. Crystal growth propagates a sequence of bits while mechanically-induced scission creates new growth fronts. Together, these processes exponentially increase the number of crystal sequences. In the system we describe, sequences are arrangements of DNA tile monomers within ribbon-shaped crystals. 99.98% of bits are copied correctly and 78% of 4-bit sequences are correct after 2 generations; roughly 40 sequence copies are made per generation. In principle, this process is accurate enough for 1000-fold replication of 4-bit sequences with ~50\% yield, replication of longer sequences, and Darwinian evolution. We thus demonstrate that neither enzymes nor covalent bond formation are required for robust chemical sequence replication. Petra Schwille Towards a possible origin of regulated cell division Peter Stadler Origins of Complex Regulation: A Tale of RNA and Chromatin Peter F Stadler (U Leipzig) joint work with Sonja J Prohaska, David C Krakauer, Christian Arnold, Lydia Steiner, Irma Lozada-Chaves Modern organism rely on complex regulatory circuits that involve control at many different levels making use of a plethora of different modes of molecular interactions. Despite the central role of the notion of ``regulation'' in modern biology, we still lack a deeper theoretical understanding. Here, I will discuss the evolutionary history and properties of the epigenetic layer of regulation with an emphasis on its computational aspects. Protein complexes that are capable of simultaneous reading and writing of histone modification can be seen as physical instantiations of rewriting rules -- and thus of an essentially digitial computer. A second aspect that will be discussed is the role of the many evolutionarily young non-coding RNAs that have been identified as additional layers of regulation. It may not be surprising that they are tied to epigenetic phenomena in manifold ways. Sonja J Prohaska, Peter F. Stadler, and David C. Krakauer. Innovation in gene regulation: The case of chromatin computation. J. Theor. Biol., 265:27-44, 2010. Irma Lozada-Chávez, Peter F. Stadler, and Sonja J. Prohaska. Hypothesis for the modern RNA world: a pervasive non-coding RNAbased genetic regulation is a prerequisite for the emergence of multicellular complexity. Orig. Life Evol. Biosph., 41:587-607, 2011. John Sutherland Origins of Life Systems Chemistry The lecture will cover recent advances in systems chemistry syntheses of the informational, catalytic and compartment–forming molecules thought necessary for the emergence of life. Tsvi Tlusty Self-replication in a life full of errors: the ribosome as a molecular decoder The origin of Life is associated with the emergence of molecular recognition systems that can convey, process and store information in a noisy biochemical environment. This stochastic biophysical setting poses a tough problem: how to construct information processing systems that are efficient and yet error-resilient? We will discuss this challenge in the “modern” context of the ribosome, the molecular engine of the present self-replication machinery: In order to synthesize proteins, ribosomes have to select the correct building blocks from a large pool of similar substrates, and inaccurate or inefficient selection might be devastating to the organism. We will examine the performance of the ribosome in this task and the possible role of its large conformational changes. The analysis suggests a simple generic mechanism that may be relevant also in the context of more primitive molecular machinery. Stéphane Udry Super-Earths and Neptunemass planets: a window to planetary-system diversity Our understanding of planetary systems has tremendously changed over the past 15 years after the detection of exoplanets orbiting other stars similar to the Sun. I will report on the results of a 10-year survey carried out at the La Silla Observatory with the HARPS spectrograph to detect and characterise an emerging large population of exoplanets in the super-Earth and Neptune-mass regime, not observed in the Solar System. The detection of a sufficiently large number of low-mass planets allows us to study the statistical properties of their orbital elements, the correlation of host-star properties with the planet masses, as well as the occurrence rate of planetary systems around solar-type stars. These results will be discussed in comparison with the recent findings of the Kepler satellite, bringing light to our understanding of the formation and evolution of planetary systems, with a focus on the ones in the habitable zone of their parent stars. Prospects for the future detection of Earth twins will be discussed as well.