{"id":9036,"date":"2024-12-06T14:08:36","date_gmt":"2024-12-06T05:08:36","guid":{"rendered":"https:\/\/www.elsi.jp\/?post_type=news_events&p=9036"},"modified":"2025-10-11T11:39:08","modified_gmt":"2025-10-11T02:39:08","slug":"representing_chemistry_underlying_rules","status":"publish","type":"news_events","link":"https:\/\/www.elsi.jp\/en\/news_events\/highlights\/2024\/representing_chemistry_underlying_rules\/","title":{"rendered":"Representing chemistry by its underlying rules to understand how evolution has selected universal pathways"},"content":{"rendered":"

ELSI researchers use a representation of chemistry by rules, which operate one level lower than molecules and reactions, to understand how simple mechanisms generate complex networks. They then study how the small number of rules and their relations tame the complexity of the large networks they generate in ways that are not apparent from the reaction networks alone. Problems of biochemical function sometimes turn out to have repetitive and even program-like structures in such spaces. One can identify naturally occurring solutions like universal metabolic pathways as optima that minimise programme complexity or energy cost in chemical spaces that are comprehensible to us and to selection because of regularities imposed by the rules.<\/strong>
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Image 1. Example of the \u201cmessy\u201d reaction networks generated by five reaction rules. Chemical species are represented by filled circles, with molecules shown adjacent. Colors indicate the kind of sugar (red = aldose, blue = ketose, green = 2-phosphates), and white numbers give the carbon count in each sugar. Heavy colored lines represent reactions, with different colors corresponding to different rules. Open circles and thin lines show the sets of molecules into or out of reactions, which make this a stoichiometric network. Credit: the authors<\/div>\n

 
\nA common reason many natural processes are complex is that objects can’t undergo changes individually: one object can change only if other objects also change as part of the same event.\u00a0 For example, Carbon dioxide can only turn to methane if other molecules donate hydrogen and remove oxygen.\u00a0 An egg cell can only become an embryo when it fuses with a sperm. You can only play a game of Bridge when you have four players.\u00a0 The need to have multiple parts \u201clined up\u201d to change together can cause remote parts of a system to constrain each other, making the system hard to understand, predict, or control. (Who hasn\u2019t heard Bridge players unable to start their game, saying, “We can’t find a fourth!”)\u00a0 Chemists have a word, stoichiometry<\/em>, for this kind of change in which a whole set of objects is converted together at once, and chemical reaction networks are also known as stoichiometric networks<\/em>.
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\nStoichiometric networks are often large and complicated, with many species and reactions, and it can be hard to understand how they couple cause and effect. Yet we know many cases in which evolution has sifted through this complexity to find specific solutions and maintain them for a long time. Examples include the universal pathways of metabolism, such as the Calvin-Benson-Bassham cycle for fixing CO2<\/sub> to biological sugars (the name given to the process by which inorganic carbon enters living systems). Do the chemical networks we find on planetary surfaces and in cells have hidden simplicity that makes searching and controlling them possible for the kinds of random processes needed to account for life\u2019s origin?\u00a0 The answer is yes: many networks in nature have reactions generated by just a few rules<\/em>.\u00a0 In chemistry, these are known as the reaction mechanisms. The difference between a reaction and a rule is that reactions convert specific molecules: rules describe the chemical bonds that change, no matter what molecules they occur in, for example, changing a bonded \u2013H to a bonded \u2013OH. If one can control the rules, one may be able to understand and evolve the networks they produce.<\/p>\n

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A project by ELSI\u2019s Specially Appointed Professor Eric Smith and Specially Appointed Associate Professor Harrison Smith, and their collaborator Jakob Andersen, Associate Professor at the University of Southern Denmark (himself a former ELSI EON fellow), aimed to understand how rules simplify reaction networks, and how we can use this simplicity to identify the reasons evolution has produced a universal Calvin cycle and maintained it for more than 3.5 billion years.\u00a0 They used a dedicated computer language for rule-based computational chemistry, called M\u00d8D, written by Andersen and colleagues, to model the messy networks generated by only five rules in the absence of selection for individual chemical species (Fig.1).\u00a0 They then studied the common features among all reaction sequences that do what the Calvin cycle does: shuffle CH2<\/sub>O groups between sugars of different lengths without loss. They were able to show that solutions to this problem can have an algorithmic<\/em> structure, with an initialisation reaction and a repeated chemical WHILE loop, followed by a RESET reaction (Fig.2). Among all solutions of this kind, the biological Calvin cycle is the shortest one from feasible chemicals. Also, it requires one of the lowest consumptions of chemical work to perform under typical biological conditions.<\/p>\n

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The researchers are currently using M\u00d8D and similar methods to study more complex and older reaction networks, such as those in prebiotic geochemistry and the earliest metabolisms. Andersen and others have also used the same methods to solve problems in metabolic engineering and optimisation.<\/p>\n

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Image 2. Solutions for the Calvin cycle conversion problem, written on a diagram where for every reaction input or output, the horizontal axis gives the carbon count of the aldose sugar and the vertical axis gives the carbon count of the ketose sugar, in that input or output. Reactions are links in the graph, colored according to the rule that generates each reaction. Legend gives these rule types, and also tells where the molecules of dihydroxyacetone-phosphate (DHAP) or glyceraldehyde-phosphate (GAP) are added, or ribulose-5-phosphate (Ru5P) is withdrawn. Each panel shows a separate solution; the final panel shows the initiation loop (lower left) and the repeated looping procedure (center) that all the solutions share. The biological Calvin cycle is the second panel. It and the first panel are the two shortest possible solutions, counted by the number of links. (All similar cycles passing through larger sugars will add a further link where the first two panels show the small blue circle, where no reaction is needed.) The first panel, unlike the Calvin cycle realized in biology, requires a chemical that, while computationally possible, is not used anywhere in living systems. Credit: the authors<\/div>\n
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Journal<\/td>\nPLoS Complex Systems<\/td>\n<\/tr>\n
Title of the paper<\/td>\nRules, hypergraphs, and probabilities: The three-level analysis of chemical reaction systems and other stochastic stoichiometric population processes<\/td>\n<\/tr>\n
Authors<\/td>\nEric Smith1,2,3*, <\/sup>Harrison B. Smith1,4<\/sup>, Jakob Lykke Andersen5<\/sup><\/td>\n<\/tr>\n
Affiliations<\/td>\n\n
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  1. Earth-Life Science Institute, Tokyo Institute of Technology, Tokyo, Japan<\/li>\n
  2. Santa Fe Institute, Santa Fe, New Mexico, United States of America<\/li>\n
  3. Department of Chemistry and Biochemistry, Georgia Institute of<\/li>\n
  4. Technology, Atlanta, Georgia, United States of America<\/li>\n
  5. Blue Marble Space Institute of Science, Seattle, Washington, United States of America<\/li>\n
  6. Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark<\/li>\n<\/ol>\n<\/td>\n<\/tr>\n
DOI<\/td>\n10.1371\/journal.pcsy.0000022<\/a><\/td>\n<\/tr>\n
Online published date<\/td>\n5 December 2024<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"featured_media":9037,"template":"","news_events_cat":[9],"acf":[],"_links":{"self":[{"href":"https:\/\/www.elsi.jp\/wp-json\/wp\/v2\/news_events\/9036"}],"collection":[{"href":"https:\/\/www.elsi.jp\/wp-json\/wp\/v2\/news_events"}],"about":[{"href":"https:\/\/www.elsi.jp\/wp-json\/wp\/v2\/types\/news_events"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.elsi.jp\/wp-json\/wp\/v2\/media\/9037"}],"wp:attachment":[{"href":"https:\/\/www.elsi.jp\/wp-json\/wp\/v2\/media?parent=9036"}],"wp:term":[{"taxonomy":"news_events_cat","embeddable":true,"href":"https:\/\/www.elsi.jp\/wp-json\/wp\/v2\/news_events_cat?post=9036"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}