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Prebiotic metabolic pathways, another naturalistic hypothesis of the origin of life

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Guest post by Evgeny Selensky:

An interesting summary of an abiogenetic hypothesis of prebiotic metabolic networks can be found here. The bottom line is, it is interesting but it raises many serious questions.

The hypothesis is based on the observed similarity of the core structure of metabolic networks across all organisms. It is then hypothesised that the core must have had an early evolutionary origin.

As is expected of a naturalistic hypothesis, it relies on extremely favourable starting conditions (the lucky concentrations of all necessary reagents in an Archean ocean, the right temperature, etc.) and other physico-chemical constraints, which, according to its proponents, helped form a prebiotic metabolic complex.

The summary makes a correct distinction between thermodynamically controlled reactions and self-replication. There is no need in replication mechanisms as long as a given product is constantly re-made because it is chemically stable. The question then is, how then did the information translation apparatus observed in all contemporary organisms arise?

Physico-chemical constraints cannot by themselves cause information translation because for translation to happen, a material symbol must be physico-chemically inert and independent of the effect it evokes in the system. Furthermore, the rules of translation from symbols (e.g. nucleotides of messenger RNAs) to their meanings (polypeptides) must be arbitrary with respect to the physico-chemical necessity that holds the system together, in order to get ‘unlocked’ from this necessity for the system to be able to encode messages. In genetic translation, this arbitrariness is ensured by the absence of any physico-chemical bias in nucleotide polymerisation: every one of the four nucleotides can polymerise every other in water.

Chemistry cannot produce the different roles that the material components of the translation apparatus play, namely: the symbol, the protocol and the effect! To organize translation it is necessary to impose an epistemic cut:

  • Code/Interpreter
  • Sign/Matter
  • The measured/The measurer
  • The controlled/The controller
  • Motion of matter/Boundary conditions

Such an epistemic cut, which is the essence of organization, is infeasible purely physico-chemically, i.e. as a consequence of solely the motion of matter. The reliance exclusively on physico-chemical constraints to produce organization is the primary category error in all naturalistic origin of life models, including this one.

Organization (rules of behaviour as opposed to physico-chemical constraints) is only possible via intelligence external to the system being organized. Since intelligence is the only empirically warranted cause of organization, it must have been the cause of biological organization as well. There is no other option.

Further reading

Abel (2015): Primordial Prescription: The Most Plaguing Problem of Life Origin Science.

H. Pattee (2001): The physics of symbols: Bridging the epistemic cut, Biosystems, v. 60,

Comments
We are not committed with the RNA World proposition and cannot offer a justified alternative. Some of the commonly accepted pre-biotic supports and guides for oligomerization reactions, e.g., from mineral surfaces such as clays [125], would be non-specific enough to accept diverse kinds of monomers. Any choice among the possibilities would have to rely upon robust experimentation. In this possibly highly conflictive area, we remain.
Self-Referential Encoding on Modules of Anticodon Pairs—Roots of the Biological Flow System Romeu Cardoso Guimarães Koji Tamura, Academic Editor Life (Basel). 7(2): 16. doi:  10.3390/life7020016 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492138/pdf/life-07-00016.pdf
And the most fundamental question remains unanswered: Where’s the beef? :) Complex functionally specified informational complexity?Dionisio
July 30, 2017
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Cellular structures and functions are composed by a network that may be divided into a mostly internal segment of macromolecules, the proteins and the nucleic acids, and another of micromolecules, that communicate and exchange intimately with the environment. The genetic encoding/decoding system is a key mechanism in both of these processes. It participates in the informational, the polymer sequence order-based self-referential cycle that is the cellular nucleoprotein core, the specifically endogenous and molecular identifier of living beings [...]
Self-Referential Encoding on Modules of Anticodon Pairs—Roots of the Biological Flow System Romeu Cardoso Guimarães Koji Tamura, Academic Editor Life (Basel). 7(2): 16. doi:  10.3390/life7020016 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492138/pdf/life-07-00016.pdf
Complex functionally specified informational complexity?Dionisio
July 30, 2017
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The analysis presented here reveals that the second stage of genetic code development (acquiring the ability to recognize all 61 sense codons quickly and unambiguously) was nearly complete in LUCA. Only one or two sense codons were outside LUCA’s sense codon repertoire. In summary, this paper contains two main messages. Firstly, the importance of the extremely regular structure of the genetic code for understanding the evolution of life is brought into focus. Secondly, LUCA greatly resembled present-day Archaea in terms of its tRNA set, while Bacteria and Eucarya have diverged from this situation.
Anticodon Modifications in the tRNA Set of LUCA and the Fundamental Regularity in the Standard Genetic Code Peter T. S. van der Gulik and Wouter D. Hoff PLoS One. 11(7): e0158342. doi:  10.1371/journal.pone.0158342 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959769/pdf/pone.0158342.pdf
Where's the beef? :) Complex functionally specified informational complexity?Dionisio
July 30, 2017
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The evolutionary origin of the standard genetic code (SGC) is widely viewed as a central open problem in the evolution of life [...] Key questions in the field focus on early steps in the evolution of the SGC, such as: what is the origin of the first tRNA and what is the amino acid that it encoded; how did this first tRNA give rise to a set of 20 encoded amino acids?
Anticodon Modifications in the tRNA Set of LUCA and the Fundamental Regularity in the Standard Genetic Code Peter T. S. van der Gulik and Wouter D. Hoff PLoS One. 11(7): e0158342. doi:  10.1371/journal.pone.0158342 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959769/pdf/pone.0158342.pdf
Complex functionally specified informational complexity?Dionisio
July 30, 2017
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[...] synthetic lifeforms employing rewritten genetic codes can be produced by a number of different methods. These methods will widen the scope of synthetic life research, bringing unique insights into protein chemistry and biology as well as a wide range of applications.
Future of the Genetic Code Hong Xue and J. Tze-Fei Wong* Koji Tamura, Academic Editor Life (Basel). 7(1): 10. doi:  10.3390/life7010010 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370410/pdf/life-07-00010.pdf
Complex functionally specified informational complexity?Dionisio
July 30, 2017
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The cooperation between RNA and protein founded on the triplet genetic code is pivotal to life, and the development of the standard genetic code is the centerpiece in life’s emergence. The sharing of the same protein alphabet by all living species suggests that the alphabet determined by the standard code predated the earliest divergence of organisms.
Future of the Genetic Code Hong Xue and J. Tze-Fei Wong* Koji Tamura, Academic Editor Life (Basel). 7(1): 10. doi:  10.3390/life7010010 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370410/pdf/life-07-00010.pdf
Complex functionally specified informational complexity?Dionisio
July 30, 2017
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[...] RNA is too complex to have arisen prebiotically, it is highly unstable, and is generally a weak catalyst. Another problem is the lack of resources (i.e., nucleotides) for replication of RNA.
Coenzyme world model of the origin of life Alexei A. Sharov Biosystems. 144: 8–17. doi:  10.1016/j.biosystems.2016.03.003 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4875852/pdf/nihms776782.pdf
duh! we knew that. :)Dionisio
July 30, 2017
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Reconstruction of past evolutionary events is an exciting challenge; it requires integration of huge amounts of facts and theoretical approaches in order to filter out the most likely scenario of the origin of specific organs. It is even more difficult to approach the ultimate challenge – understanding the origin of life.
Coenzyme world model of the origin of life Alexei A. Sharov Biosystems. 144: 8–17. doi:  10.1016/j.biosystems.2016.03.003
oh, really? :)Dionisio
July 30, 2017
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The origin of life means the emergence of heritable and evolvable self-reproduction. [...] life originated from simple but already functional molecules, and its gradual evolution towards higher complexity was driven by cooperation and natural selection.
Coenzyme world model of the origin of life Alexei A. Sharov Biosystems. 144: 8–17. doi:  10.1016/j.biosystems.2016.03.003
quasi-scientific hogwash on steroids? where's the beef? :)Dionisio
July 30, 2017
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Constructivism is a valuable addition to biosemiotics because it emphasizes the activity of agents in self-construction, self-reproduction, and development of sign relations. New sign relations emerge as modifications of older sign relations and employ already available tools, resources, and subagents. New levels of semiosis emerge via functional integration of interacting agents (meta-system transition). Multilevel semiotic networks are needed to support the plasticity, robustness, and evolvability of organisms.
Evolutionary biosemiotics and multilevel construction networks. Sharov AA Biosemiotics. 9(3):399-416. doi: 10.1007/s12304-016-9269-0. http://alexei.nfshost.com/biosem/Sharov_multi-level_2016_NIHversion.pdf
Complex functionally specified informational complexity?Dionisio
July 30, 2017
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Organisms use signs to establish relations between their functional components and the environment (both external and internal), and thus, signs are always connected into semiotic networks. Both plasticity and robustness in organisms require multiple alternative signaling pathways to switch to in the case of malfunction, as well as additional compensatory mechanisms to ameliorate the negative effects of external and internal disturbances.
Evolutionary biosemiotics and multilevel construction networks. Sharov AA Biosemiotics. 9(3):399-416. doi: 10.1007/s12304-016-9269-0. http://alexei.nfshost.com/biosem/Sharov_multi-level_2016_NIHversion.pdf
Complex functionally specified informational complexity?Dionisio
July 30, 2017
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Eventually organisms developed complex sense organs and acquired a capacity to integrate incoming signals into meaningful categories representing real objects and situations (e.g., food items, partner agents, or enemies) and predict events using models. This capacity may have emerged in single-cell organisms but became fully developed in multicellular organisms with a nervous system.
Evolutionary biosemiotics and multilevel construction networks. Sharov AA Biosemiotics. 9(3):399-416. doi: 10.1007/s12304-016-9269-0. http://alexei.nfshost.com/biosem/Sharov_multi-level_2016_NIHversion.pdf
Wow! That's really cool! And very well explained in all details. :) However, I still prefer Cinderella's story, where a pumpkin turned into an elegant carriage, mice became beautiful horses and a grumpy grasshopper was hired as a polite cochero. At least all that makes more sense, doesn't it? :) Complex functionally specified informational complexity?Dionisio
July 30, 2017
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To overcome this limitation, organisms developed epigenetic mechanisms to modify logical gates on demand.
Evolutionary biosemiotics and multilevel construction networks. Sharov AA Biosemiotics. 9(3):399-416. doi: 10.1007/s12304-016-9269-0. http://alexei.nfshost.com/biosem/Sharov_multi-level_2016_NIHversion.pdf
Does such a statement imply that biological organisms do things purposely? Really? Wow! Complex functionally specified informational complexity?Dionisio
July 30, 2017
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Note that the paper referenced @15 is sprinkled with pseudoscientific nonsense that evidently fails to answer the most fundamental question in science research reporting: Where’s the beef?Dionisio
July 30, 2017
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There is no consensus on the definition of sign in biosemiotics. [...] a ribosome has no internal representation of an amino acid as object and it does not “know” that it makes proteins. Instead, a ribosome detects if a triplet of nucleotides in the mRNA matches to the anticodon sequence of the incoming tRNA molecule loaded with an amino acid and then makes a peptide bond. [...] a ribosome simply gets a signal that indicates readiness for the reaction and then uses the catalyst tool to finish the action.
Evolutionary biosemiotics and multilevel construction networks. Sharov AA Biosemiotics. 9(3):399-416. doi: 10.1007/s12304-016-9269-0. http://alexei.nfshost.com/biosem/Sharov_multi-level_2016_NIHversion.pdf
Complex functionally specified informational complexity?Dionisio
July 30, 2017
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Note that the paper referenced @13 is sprinkled with pseudoscientific nonsense that flatly fails to answer the most fundamental question in science research reporting: Where's the beef? Oh well, what else is new?Dionisio
July 30, 2017
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It is no doubt quite difficult to solve the riddle of the origin of life. In order to solve the riddle on the origin of life, it is important to understand the process by which the fundamental life system was formed, which is composed of three major elements: genes, genetic code, and proteins. [...] the most important step in solving the riddle of the origin of life is to make clear the process by which the fundamental life system, composed of genes, genetic code, and proteins, was established on the primitive Earth. [...] there are still some other difficult problems that must be overcome to explain the evolutionary process to the emergence of life. Until now, researchers have tried to understand, using the bottom-up approach, how the first life emerged on the primitive Earth, but it has been so far proven impossible to solve the riddle of the origin of life. It is principally impossible to elucidate the formation process of the fundamental life system composed of genes, genetic code, and proteins.
Evolutionary Steps in the Emergence of Life Deduced from the Bottom-Up Approach and GADV Hypothesis (Top-Down Approach) Kenji Ikehara Life (Basel). 6(1): 6. doi:  10.3390/life6010006 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810237/pdf/life-06-00006.pdf
Dionisio
July 29, 2017
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To remove marker bias and expand the experimental scope of deletion libraries, construction of a bona fide prototrophic collection from a wild-type strain will be required. This work underscores the degree to which systematic genetics and genomics has advanced our understanding of genotype–phenotype relationships. The resolution of comparative fitness profiling is highly sensitive, providing detailed biological insight and revealing methodological biases inherent in strain construction.
Comparative functional genomic screens of three yeast deletion collections reveal unexpected effects of genotype in response to diverse stress Erica Acton,1,2 Amy Huei-Yi Lee,1,3 Pei Jun Zhao,5 Stephane Flibotte,1,4 Mauricio Neira,1 Sunita Sinha,1 Jennifer Chiang,1 Patrick Flaherty,6 Corey Nislow,1 and Guri Giaever1 Open Biol. 7(6): 160330. doi:  10.1098/rsob.160330
Dionisio
July 29, 2017
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Further confirmation of these results with the integration of other experimental data-sets will provide deeper insights into the regulatory events mediating the metabolic phenotype.
Systematic Analysis of Transcriptional and Post-transcriptional Regulation of Metabolism in Yeast Emanuel Gonçalves,1 Zrinka Raguz Nakic,2 Mattia Zampieri,2 Omar Wagih,1 David Ochoa,1 Uwe Sauer,2 Pedro Beltrao,1,‡* and Julio Saez-Rodriguez PLoS Comput Biol. 13(1): e1005297. doi:  10.1371/journal.pcbi.1005297
Dionisio
July 29, 2017
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Signal transduction is an important cellular mechanism that allows cells to sense and respond to environmental cues. [...] interactions among different biological processes occur and are very important to coordinate the whole phenotype of the cell. [...] the systematic identification and functional annotation of these regulatory interactions is still a challenge.
Systematic Analysis of Transcriptional and Post-transcriptional Regulation of Metabolism in Yeast Emanuel Gonçalves,1 Zrinka Raguz Nakic,2 Mattia Zampieri,2 Omar Wagih,1 David Ochoa,1 Uwe Sauer,2 Pedro Beltrao,1,‡* and Julio Saez-Rodriguez PLoS Comput Biol. 13(1): e1005297. doi:  10.1371/journal.pcbi.1005297
Dionisio
July 29, 2017
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Cells sense and react to extracellular stimuli with coordinated intracellular responses conveying transcriptional, protein and metabolic changes [...] The increasing accumulation of molecular measurements have provided unprecedented knowledge of the cellular molecular adaptation, nonetheless the robust identification of the regulatory interactions underpinning these changes is still a challenge [...]
Systematic Analysis of Transcriptional and Post-transcriptional Regulation of Metabolism in Yeast Emanuel Gonçalves,1 Zrinka Raguz Nakic,2 Mattia Zampieri,2 Omar Wagih,1 David Ochoa,1 Uwe Sauer,2 Pedro Beltrao,1,‡* and Julio Saez-Rodriguez PLoS Comput Biol. 13(1): e1005297. doi:  10.1371/journal.pcbi.1005297
Dionisio
July 29, 2017
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Phosphorylation is a broad regulatory mechanism with implications in nearly all processes of the cell. However, a global understanding of possible regulatory mechanisms remains elusive. We believe these findings illustrates the usefulness of this approach for future integrative studies interested in studying metabolic regulation.
Systematic Analysis of Transcriptional and Post-transcriptional Regulation of Metabolism in Yeast Emanuel Gonçalves,1 Zrinka Raguz Nakic,2 Mattia Zampieri,2 Omar Wagih,1 David Ochoa,1 Uwe Sauer,2 Pedro Beltrao,1,‡* and Julio Saez-Rodriguez PLoS Comput Biol. 13(1): e1005297. doi:  10.1371/journal.pcbi.1005297
Dionisio
July 29, 2017
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Cells react to extracellular perturbations with complex and intertwined responses. Systematic identification of the regulatory mechanisms that control these responses is still a challenge and requires tailored analyses integrating different types of molecular data. This work provides a novel genome-scale integrative analysis to propose putative transcriptional and post-translational regulatory mechanisms of metabolic processes.
Systematic Analysis of Transcriptional and Post-transcriptional Regulation of Metabolism in Yeast Emanuel Gonçalves,1 Zrinka Raguz Nakic,2 Mattia Zampieri,2 Omar Wagih,1 David Ochoa,1 Uwe Sauer,2 Pedro Beltrao,1,‡* and Julio Saez-Rodriguez PLoS Comput Biol. 13(1): e1005297. doi:  10.1371/journal.pcbi.1005297
Dionisio
July 29, 2017
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The evolutionary origins of metabolism, in particular the emergence of the sugar phosphates that constitute glycolysis, the pentose phosphate pathway, and the RNA and DNA backbone, are largely unknown. [...] the origin of complex multistep metabolic pathways is difficult to explain solely by Darwinian selection in the absence of a chemical template. The parallel occurrence of glucose catabolism and anabolism as driven by a simple, nonenzymatic chemistry might be able to explain how central metabolism originated in the defined compartment of the cell and how it escaped equilibrium, thereby helping to understand why glucose metabolism became universally important for life.
Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice Christoph B. Messner, Paul C. Driscoll, Gabriel Piedrafita, Michael F. L. De Volder and Markus Ralsera,b, Proc Natl Acad Sci U S A. 114(28): 7403–7407. doi:  10.1073/pnas.1702274114
[...] might be able to explain [...] [...] helping to understand why [...] Work in progress... stay tuned... let's wait and see... keep an eye on this.Dionisio
July 29, 2017
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It is still unknown how an early metabolism produced the sugar phosphates central for life. The reaction further hints that the earliest anabolic enzymes could have been as simple as single amino acids.
Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice Christoph B. Messner, Paul C. Driscoll, Gabriel Piedrafita, Michael F. L. De Volder and Markus Ralsera,b, Proc Natl Acad Sci U S A. 114(28): 7403–7407. doi:  10.1073/pnas.1702274114
Dionisio
July 29, 2017
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To organize translation it is necessary to impose an epistemic cut:
Code/Interpreter Sign/Matter The measured/The measurer The controlled/The controller Motion of matter/Boundary conditions
Very well identified requirements.Dionisio
July 29, 2017
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Excellent!Upright BiPed
July 27, 2017
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Dionisio, My pleasure!EugeneS
July 27, 2017
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Otlichno!!! Bolshoye spasibo!Dionisio
July 27, 2017
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