Information Storage and Processing in Biological Systems: A seminar course for the Natural Sciences Sept 16 Introduction / DNA, Gene regulation Sept 18 Translation and Proteins Sept 23 Enzymes and Signal transduction Sept 25 Biochemical Networks Sept 30 Simple Genetic Networks Oct 2 Adventures in Multicellularity Nov 6 Evolution, Evolvability and Robustness
Reading List for Part 1 Chapters 1-3 “The Thread of Life” S. Aldridge Cambridge University Press. 1996. “Genes & Signals” by Mark Ptashne and Alexander Gann. (2002) CSHL Press. -------------------------------------------------------------------------------------------- From molecular to modular cell biology. (1999) L. H. Hartwell, J. J. Hopfield, S. Leibler and A. W. Murray. Nature 402 (SUPP): C47-C52. It’s a noisy business! Genetic regulation at the nanomolar scale. H. Harley and A Arkin. Trends In Genetics February 1999, volume 15, No. 2 The challenges of in silico biology. (2000) B. Palsson. Nature Biotechnology 18: 1147-1150.
What is “biological information” and how is it “Stored” and Processed”? M.C. Escher Spirals
What is “biological information”? Genetic (DNA and RNA)
What is “biological information”? Genetic (DNA and RNA) Epigenetic (DNA modification)
What is “biological information”? Genetic (DNA and RNA) Epigenetic (DNA modification) Non-Genetic Inheritance (template dependent replication) paragenetic
Global patterning of organelles and cilia in Paramecium relies on paragenetic information and is template dependent. Another example is Mad Cow Disease
What is “biological information”? Genetic (DNA and RNA) Epigenetic (DNA modification) Non-Genetic Inheritance (template dependent replication) Physiological-Cellular Level ( Structural/Metabolism/Signal Transduction)
Simplified Connectivity of Map of Metabolism Each node represents a chemical in the cell ( E. coli ) Each connection represents an enzymatic step or steps
What is “biological information”? Genetic (DNA and RNA) Epigenetic (DNA modification) Non-Genetic Inheritance (template dependent replication) Physiological-Cellular Level ( Structural/Metabolism/Signal Transduction) Physiological- Organism Level ( Structural/Metabolism/Signal Transduction, Development, Immune System)
What is “biological information”? Genetic (DNA and RNA) Epigenetic (DNA modification) Non-Genetic Inheritance (template dependent replication) Physiological-Cellular Level ( Structural/Metabolism/Signal Transduction) Physiological- Organism Level ( Structural/Metabolism/Signal Transduction, Development, Immune System) Populations (Population dynamics, Evolution)
What is “biological information”? Genetic (DNA and RNA) Epigenetic (DNA modification) Non-Genetic Inheritance (template dependent replication) Physiological-Cellular Level ( Structural/Metabolism/Signal Transduction) Physiological- Organism Level ( Structural/Metabolism/Signal Transduction, Development, Immune System) Populations (Population dynamics, Evolution) Ecosystem (Interacting Populations, environment fl‡ populations )
The“Central Dogma” The central dogma relates to the flow of ‘genetic’ information in biological systems. DNA ÁË RNA Ë Protein DNA transcription mRNA translation Protein
Overview of Biological Systems Organization of the Tree of Life Three evolutionary branches of life: Eubacteria, Archaebacteria, Eukaryotes The macroscopic world represents a small portion of the tree.
The Eubacteria (bacteria), Archaebacteria (archae), and Eukaryotes represent three fundamental branches of life and represent two fundamental differences in organization of the cell. Major Similarities: Genetic code Basic machinery for interpreting the code Major Differences: Organization of genes Organization of the cell sub-cellular organelles in Eukaryotes * cytoskeletal structure in Eukaryotes ** No true multicellular organization in bacteria and archae (there are many single celled eukaryotes). ( debatable ) * compartmentalization of function ** morphologically distinct cell structure
Bacteria Morphologically “simple” - shape defined by cell surface structure. Transcription (reading the genetic message) and Translation (converting the genetic message into protein) are coupled- they take place within the same compartment (cytoplasm).
Compartmentalization of Function in eukaryotic cells Transcription (reading the genetic message) and Translation (converting the genetic message into protein) occur in different compartments in the eukaryotic cell.
Example of single celled eukaryotic organisms Morphological diversity (cytoskeleton as well as cell surface structures)
There are many distinct morphological cell types within a multicellular organism. Morphological diversity arises from cytoskeletal networks - architectural proteins
Some ‘Model’ Experimental Eukaryotic Organisms Caenorhabditis elegans Saccharomyces cerevisiae (round worm) Drosophila melanogaster (fruit fly) mouse Antirrhinum majus Zebrafish Arabidopsis thaliana (snapdragons )
Bacteriophage (Phage) and Viruses 1) genetic material / nucleic acid 2) protective coat protein The information for their own replication and the means to “target” the correct cell/host but no interpretive machinery
Genotype The genetic constitution of an organism. Phenotype The appearance or other characteristic of an organism resulting from the interaction of its genetic constitution with the environment.
Constraints in Biological Systems Chemical/Physical constraints • stability of biological material • reaction rates and diffusion rates - properties of biochemical reactions (enzymes) differ from chemical reactions • time dependency of many steps - time scales over many orders of magnitude for different steps -receptor ligand binding msec -biochemical response sec -genetic response minutes- hours-days • statistical properties of ‘small-scale” chemistry, i.e. where concentration of reacting molecules is low. Evolutionary constraints • a biological system is constrained by it’s own evolutionary history (and also ‘biological’ history)
“Alarm clock” from the movie Brazil Evolution of new functions is rarely de novo invention but is typically due to the modification of pre-existing functions/structures.
Modularity • Is the cell/organism designed in a modular fashion? • Can we approximate cell behavior into modules? • Can interactions of cells, individuals, organisms be treated in a similar way? Coarse graining • At what level of detail do we need to study/model a system to extract information about the underlying mechanisms? • What level of detail is required to define the “state” of the cell, the individual, the population and ecosystem…? • Can we define the “state” of the cell or only “states” of modules?
Stochastic variations and Individuality • What is the source of stochastic variation (independent of genetic variation)? • In genetically identical populations, does this play a role in adaptation? • What role do stochastic processes play in development? Robustness • Despite stochastic variations, many cellular processes are extremely robust (genetic networks, biochemical networks, cell divisions, development,…) • How does the cell overcome the limitations imposed by stochastic variations? • Where does robustness arise? Is it a network property?
Redundancy - Many biological processes are duplicated so that the same function is present in multiple elements. Mutations (changes in genotype) may have no apparent phenotype or one that is less severe than expected. - Many biological systems are degenerate, they can occur by alternative pathways. Complexity “the whole is greater than the sum of its parts.”
Genotype ‡ Phenotype Can we understand the mechanisms and processes that shape the expression of genetic variation in phenotypes?
The Natural History of Dictyostelium discoideum Adventures in Multicellularity The social amoeba (a.k.a. slime molds)
The Natural History of Dictyostelium discoideum Adventures in Multicellularity The social amoeba (a.k.a. slime molds)
The Natural History of Dictyostelium discoideum Adventures in Multicellularity The social amoeba (a.k.a. slime molds)
DNA Basics Four bases A - adenine T - thymine C - cytosine G - guanine anti- parallel double stranded structure with specific bonding between the two strands: A ‡ T base pairing C ‡ G base pairing
DNA Structure • DNA is composed of two strands A - T • Each strand is composed of a sugar phosphate backbone C - G with one of four bases attached to each sugar G - C A - T •The arrangement of bases along a strand is aperiodic T - A G - C • The two strands are arranged anti-parallel G - C G - C • There is base specific pairing between the strands such T - A that A pairs with T and C with G, consequently knowing the sequence of one strand gives us the sequence of the opposite strand.
Chemical Structure of DNA The Double Helix
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