Recall Darwinian Chemistry – Replication, Mutation, SelectionSymmetry breaking also has to happen spontaneously (e.g., to favor a specific chirality)The first life form: Improbable or Inevitable?Fractals - Why does higher complexity always form?Rebuilding the RNA World, one function at a timeHypercycles and MetabolismPrimitive cells in the primordial world: Distinction between self and non-selfModern eukaryotes formed through endosymbiosisMolecularly: Transitions to an RNA-protein, then the modern DNA-RNA-protein worldChemical evolution took a billion years, but left few tracesBut modern biochemistry carries evolutionary roots that can partially be traced back.CHEM 451 1st Edition Lecture 2 Outline of Last Lecture II. The molecules at the rootIII.How “complex” organic molecules formA.Basic building blocksB.Building larger, “biological” moleculesC.Second Law of ThermodynamicsIV. Assembly of biopolymers I. Darwinian Chemistry = Driving force of Evolution: Replication, Mutation, Selection Outline of Current Lecture V. Darwinian Chemistry, Continueda. Briggs-Rauscher Oscillating Chemical ReactionVI. Symmetry breakingVII. Levinthal’s paradoxVIII. FractalsIX. Hypercycles and Metabolisma. Self vs. non-selfX. EndosymbiosisCurrent Lecture Recall Darwinian Chemistry – Replication, Mutation, SelectionAs long as there is an energy source that allows you to stay away from equilibrium and a molecule that can store information in some form, replication can occurReplication coerces errors or mutations induced by chemical reactions, creating a quasispecies (different sequences but related by biotype; may have different functions)Selection of the fittest typesThis phenomenon can be re-enacted in the test tube via detergent enzymes (proteins evolve to be heat-stable)[Video: self-assembly process]Bottle caps reassemble so that green and white caps arrange in an alternating sequenceLike repels, opposites attractThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.Briggs-Rauscher Oscillating Chemical ReactionMaize switches to blue and back to maize2 meta-stable states alternate back and forth: iodine has different colors in each of its oxidation statesCharacteristic of reactions with feedback loops, which trigger the transition between meta-stable statesSelf-organization can lead to specific processes that give rise to complex patterns that change over time.Something that has replicated will be variated and only some components will survive.Efficiency of survival depends on genotypeSymmetry breaking also has to happen spontaneously (e.g., to favor a specific chirality)Examples from biology/chemistry: L vs. D-amino acidsThere needs to be a preference for one chiral shape over anotherRecall chirality: enantiomers are mirror images of one anotherHow does chirality favor one form?Different chemical connectivities are present within a systemSome sort of replication/mutation/selection process; self-sustainability of one shape over the other can break the symmetry via slight differences in concentrationThis replicates and ultimately digests the other form, amplifying purely one chiral entity (e.g., because amino acids build a better self-selecting peptide)Decay takes care of the rest of the other chiral entitySymmetry breaking is a natural consequence of bi-stable systemsThis occurs by chance!The first life form: Improbable or Inevitable?Improbability Argument: steering a mixture of all monomer building blocks of a bacterium, the odds that a single bacterium reassembles by chance is one in 10100,000,000,000Reality check: Is Nature working as a “Blind Watchmaker”?Think about a golf course…totally flat with one putting hole somewhere in the middle. If you “putt” randomly, what is the chance that you will find the single hole in the entire golf course?...this is flawed thinking.Example: Protein FoldingHundreds of millions of proteins are folding in your cells every minute. Ribosome is the big protein biosynthesis machinery that makes large quantities of individual peptides. The whole protein is able to fold in its unique structure very quickly.Levinthal’s paradox: A 100 -amino acid protein has an estimated N = 998 ≈ 3*1093 possible conformations. He assumed that the protein only had two angles (φ and ψ around α-carbon) could be changed between 3 different positions. Even if it took a pico-second to try out each possible conformation, it would take an entire lifetime to form a functional protein if only random search were at work.In reality, proteins in our cells incessantly form properly into native-states.There are many parallel pathways that go through intermediate states, making the success rate MUCH higherAny particular angle changes in parallel to other anglesOne fold creates hydrogen bonds that create energetically stable pathways for other folding stepsEach step is downhill energetically, allowing proteins to easily reach their native statesProteins fold nearly instantaneously (~micro seconds!) Exploring energetic micro statesIn other words…Protein folding is inevitable (deterministic) and so we live!There is always a (minute) driving force for any single conformational change of a polypeptide!Ex). Re-assembly of lipid bilayer in bacterium; energetically favored because lipids align, which leads to more cooperative realignmentSelf-assembly does not have to try!Fractals - Why does higher complexity always form?Fractals: complex, self-similar geometric structures from simple mathematical rules; universal innatural landscape formShape of broccoli flower vs. tree: similar rules of growthBut every tree looks unique because random events allow branches to grow in different directionsState of United States with the lowest fractal dimension is Kansas (flat landscape)Feedback loops generate such fractal geometries in nature.Rebuilding the RNA World, one function at a timePeople have performed test tube experiments to regenerate certain molecules present at the onset of lifeHeat-stable protease in a dishwasherSelection in-vitro evolution experimentsRNA Replicase: 2001, Bartel et al. – precursor to self-replicating RNA enzyme; able to use template strand to extend RNA chain ~30 nucleotidesRNA Nucleotide Synthase: 1998, Unrau & Bartel – pRpp fuses with nucleobase to create nucleotidePeptide bond formation by the ribosome is catalyzed by the RNA component: 2000,