Transcript Document
The metabolism problem: ingredients of an emerging theory Eörs Szathmáry & Chrisantha Fernando Collegium Budapest Eötvös University Budapest Thanks to Günter! Pathways of supersystem evolution metabolism MB boundary MT template BT MBT INFRABIOLOGICAL SYSTEMS General background to the talk The problems of phylogenetic reconstruction (top-down) • LUCA was too advanced • Reconstructions (e.g. Delaye et al. OLEB in press) cannot reach deep enough • The fact that metabolic enzymes are not well conserved does not mean that they were not there! • Scaffolds (pre-RNA, primitive metabolic reactions) may have disappeared without leaving a trace behind!!! • A more synthetic approach is needed • General evolutionary mechanisms must be sought Benner’s hypothetical ribo-organism (1999) Membrane? Cofactors? This raises a lot of questions • How could such a metabolic network build up? • Did the environment change or not during the process? • What was the nature of the non-enzymatic reactions producing (some of) these metabolites? • Is an autotrophic, non-enzymatic metabolism feasible? • What are the constraints on metabolic evolution in the context of supersystem evolution? Some elementary considerations O O L L •Autotrophy impossible •Autotrophy possible •Enzymatic pathways are likely to be radically new inventions •Enzymatic pathways may resemble nonenzymatic ones Organic synthesis Environment 1 Environment 2 Life Further complication of supersystem organization • The example of the Template/Boundary system: progressive distinction from the environment evolution Metabolites pass freely Metabolites are hindered Progressive sequestration • • • • Initially only templates are kept in They can evolve catalytic properties Carriers and channels can also evolve Membrane permeability can become progressively restrictive • Finally, only a very limited sample of molecules can come in • Inner and outer environments differentiate • Membrane and metabolism coevolve gradually Evolution of metabolism: primitive heterotrophy with pathway innovation Evolved enzymatic reaction A A B C B C D D A Necessarily heterotrophic protocell Assume D is the most complex A B C C B D The final stage of innovation B A C D This could be a heterotroph or autotroph (depending on the nature of A) Evolution of metabolism: primitive autotrophy with pathway retention A A B C B D C D a Retroevolution is also likely because of membrane coevolution a b c d b D c Reversible versus irreversible: the control of leakage A C B D A C Unfavourable: Favourable: Vulnerable to depletion in A Resistant to depletion in A Two contrasting modes of enzymatic pathway evolution Horowitz (1945) : retroevolution • Ancient non-enzymatic pathway: • ABCD • Progressive depletion of D, then C, then B, then A • Selection pressure for enzyme appearance in this order • Homologous enzymes will have different mechanisms Jensen (1976) enzyme recruitment (patchwork) • One possible mechanism: ambiguity and progressive evolution of specificity • Homologous enzymes will have related mechanisms • Enzyme recruitment from anywhere (opportunism) What evidence is there for the two mechanisms? • New data using the whole armamentarium of bioinformatics • It is about the evolution of PROTEIN enzymatic pathways • Could be strongly suggestive for RIBOZYME-aided metabolism (the RNA world) The example of biotin metabolism Light and Kraulis (2004) BMC Bioinformatics Homology: strict cutoff in PSIBLAST Enzymes as edges: the whole E.coli network is analyzed Minimal path length The most promiscuous 20 compounds Frequency: the number of edges where is shows up Homology versus minimal path length With the 20 Without the 20 Different types of homologous enzyme pairs Mechanistically similar Mechanistically different A statistical analysis Functionally similar Functionally dissimilar Conclusion • There is some evidence for retroevolution • BUT the dominant mode seems to fit the patchwork mechanism • Same mechanisms might worrk for an RNA world! Patchwork and retroevolution can be made compatible • A broader notion of retroevolution proposes just the (the frequent) retrograde appearance of consecutive enzymes, not that they are homologous within a pathway • Pathways retroevolving in parallel can recruit enzymes in a pacthwork manner Evolution of catalytic proteins or on the origin of enzyme species by means of natural selection • Kacser & Beeby (1984) J. Mol. Evol. • A precursor cell containing very few multifunctional enzymes with low catalytic activities is shown to lead inevitably to descendants with a large number of differentiated monofunctional enzymes with high turnover numbers. • Mutation and natural selection for faster growth are shown to be the only conditions necessary for such a change to have occurred. • The division of labour for enzymes! Evolution of connectivity: Pfeiffer et al. (2005) PloS Biology • Enzymes are initially specific for the group transferred but not for the substrates • Metabolism is based on group transfer reactions between metabolites • Without group transfer (D) only unimolecular reactions An emerging group transfer network Hubs (127126 for group 1) emerge as consequence of selection for growth rate the frequency, P(k), of metabolites participating in k reactions is given by k-c, where c is a constant coefficient An emerging network without group transfer All these ingredients (and more) must be put together • • • • • • Supersystem evolution Alternative environments Progressive sequestration Duplication and divergence of enzymes Selection for cell fitness Network complexification