QUANTITATIVE LAWS IN BIOLOGICAL CHEMISTRY
CONTENTS FREE ENERGIES, LANDSCAPES, AND FITNESS IN EVOLUTION DYNAMICS SYSTEM DESIGN PRINCIPLES CHANCE AND MEMORY INFORMATION THEORY AND ADAPTATION QUANTITATIVE IN VITRO BIOCHEMISTRY, ONE MOLECULE AT A TIME SMALL-ANGLE SCATTERING SUBCELLULAR SIGNALING DYNAMICS SINGLE-CELL BEHAVIOR MODELING GENETIC PARTS FOR SYNTHETIC BIOLOGY MODELING CELLULAR VARIABILITY PKA: PROTOTYPE FOR DYNAMIC SIGNALING IN TIME AND SPACE STOCHASTIC SIMULATION OF THE PHAGE LAMBDA GENE REGULATORY CIRCUITRY CHEMOTAXIS ?FREE ENERGIES, L 1 FREE ENERGIES, LANDSCAPES, AND FITNESS IN EVOLUTION DYNAMICS 1 1 INTRODUCTION: IS EVOLUTION THEORY IN TROUBLE? CHARLES DARWIN TRANSFORMED BIOLOGY; HOWEVER, HE PROVIDED NO ANALYTICAL TEMPLATE, AND WE STILL HAVE EXPERIMENTALLY A GREAT DEAL TO LEARN ABOUT THE DYNAMICS OF EVOLUTION, PARTICULARLY UNDER THE RESPONSE TO STRESS [1] FORTUNATELY WE CAN ANALYZE THE DYNAMICS, AND HERE WE PRO- VIDE AN ANALYTICAL FRAMEWORK WE HAVE BEEN ENGAGED IN A PROGRAM FOR SEVERAL YEARS USING MICROFABRICATED ENVIRONMENTS TO PROBE ADAPTATION AND EVOLUTION DYNAMICS [2–4] THIS CHAPTER PRESENTS SOME OF THE RESULTS THAT HAVE COME FROM THESE ATTEMPTS TO ACCELERATE EVO- LUTION IN A DETERMINISTIC MANNER THE WORK IS PERHAPS A LITTLE CONTROVERSIAL, AS TYPICALLY IT IS BELIEVED THAT EVOLUTION PROCEEDS SLOWLY OVER MANY GENERATIONS AND IN A RANDOM MANNER HOWEVER, WE DO NOT BELIEVE THIS IS NECESSARILY THE CASE, AND WE PROVIDE SOME QUANTITATIVE REASONS WE HOLD THIS OPINION WE WILL DISCUSS HOW, ON A COMPLEX LANDSCAPE OF STRESS (WHICH CORRESPONDS TO A FREE ENERGY LANDSCAPE), THE COMMON BACTERIUM E COLI CAN EVOLVE VERY HIGH RESISTANCE TO AN ANTI- BIOTIC IN ABOUT 10 HOURS, WHICH IS REMARKABLY ONLY AT MOST 20 GENERATIONS FURTHERMORE, THE RESISTANCE HAS A SURPRISINGLY PARSIMONIOUS GENETIC PROFILE: ONLY FOUR SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) HOW IS THIS POSSIBLE? HOW DID A BACTERIUM WITH THE PRESUMABLY LOW MUTATION RATE ? OF ONLY 10–9 SNPS/BASEPAIR-REPLICATION SO QUICKLY FIND THE MAGIC FOUR 1 1 INTRODUCTION: IS EVOLUTION THEORY IN TROUBLE? 1 2 FREE ENERGIES ARE CRISPLY DEFINED IN PHYSICS 1 3 FITNESS LANDSCAPES AND EVOLUTION 1 4 SPIN GLASSES, GENOMIC DYNAMICS, AND GENOMIC HETEROGENEITY 1 5 LANDSCAPE DYNAMICS OF AN ECOLOGY UNDER STRESS 1 6 AN INTRODUCTION TO SOME EXPERIMENTS 1 7 CHANGES IN THE FITNESS LANDSCAPE WITH EVOLUTION REFERENCES