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Basic Biology & some calculations [Read Chpt 1 of Berg et al.: lots of important things about Molecular Binding, Central Dogma, Entropy, DG] 1. Living is made up of complex polymers organized in one or more cells. 2. Central Dogma of Biology DNA RNA Proteins 2a. Why “junk” DNA become hot. 3.How to calculate stability of DNA 4. What introns and exons lead to tremendous genetic variability At the molecular level, the definition of life becomes somewhat simpler. All living organisms consist and make complex, heterogeneous macromolecules. They do this by ingesting the necessary substituents and make them from simple compounds. It has a way of reproducing itself, although any one member of the species need not be able to reproduce. 4 Large [Macro]Molecules (from small molecules) Biological polymers (Large molecule made from many smaller building block) • • • • DNA & RNA Nucleotides Proteins Amino Acids Carbohydrates Sugars Lipids (Fats) Fatty acids Each is used to: a. Make macromolecules/structural b. Energy Source c. Information– Storage/signaling Example: a.Make Proteins, Enzymes, Hair… b. Break down yields energy; c. amino acids used as nerve impulses (your brain largely runs on a.a. glutamate.) Major Classes of Macromolecules Hemoglobin (protein) DNA fragment (nucleic acid) Polysaccharide (carbohydrate) 0.34 nm between base pairs Lipid An atomic scale representation of each Atoms: What are we made of? Campbell We are mostly made of water (H2O): ≈75% C —very versatile: everything made of: Nucleic acids, Proteins, Lipids (fat), Carbohydrates. (Remember these families)! O —bonding, proteins, fats, nucleic acids N — proteins, genetic material Ca, P — bones The Fundamental Unit of Life is the Cell 3 types (not two!) http://bio1903.nicerweb.com/ Locked/media/ch25/25_18Tr eeOfLife.jpg Archea and Bacteria most ancient: without a nucleus (special place to put its genetic material, DNA). Otherwise bacteria and archea look a lot alike. Eukaryotes have a nucleus. Here at U of Illinois, Carl Woese in the 1970s made claim that 3 branches of life based on RNA What caused split? Don’t know but…Possibly the ingestion of a bacteria to become a mitochondria (specialized to make energy—ATP) Most Biopolymers in Body are in Cells Bacteria Prokaryotes (No nucleus) 1 mm Eukaryotic cell (us) (Has nucleus) 10-30 mm 10-100 mm (Nucleus 3-10 mm) 1014 (100 billion!) cells in body… …more stars than in Milky Way Galaxy. Yet there are 200 different types of cells in body. (Heart cell not equal to a brain cell…) Nucleus contains DNA Blueprint of cell Every cell (which has nucleus) has identical DNA [A few types, like red blood cells, are made with a nucleus but gets de-nucleated.] Each cell type expresses only a part of information in DNA (Brain cell differs from a heart cell….) How much DNA? 3 billion base pairs 1 meter In humans 46 pieces: chromosomes So a meter of DNA must be packed in 3-10 mm! What does this tell about bendability of DNA? Highly flexible. Persistence Length = 50 nm (~150 bp.) What is persistence length? Walk in one direction: how long headed in that direction (Yet can unwind and very robust in storing genetic information over a lifetime) How this is measured? Use magnetic tweezers DNA is a double helix of anti-parallel strands DNA uses a 4 letter sequence, A, T, G, C 3.4 Å 3.4 nm per ~10 base-pairs = 1 turn (360º) Must come apart for bases to be read. Minimal knowledge about Nucleotides • 4 nucleotides: A,T,G,C • A=T ≈ 2kT two hydrogen bonds G=C ≈ 4kT three hydrogen bonds • Many weak bonds…very strong overall structure. DNA is stable. We’ll calculate this in a few minutes. (Boltzman constant.) • To unzip, takes energy, ATP and proteins that act like a wedge. • Also takes proteins that act to unwrap the DNA and then act like a wedge Need to know Chemical Bonding 4 types: what are they? 1. Covalent – 100kT. Sharing of electrons. C-H Is light enough to break covalent bond? 1um=1eV; kT=1/20eV. 1um= 20kT: close (yup) 2. Ionic – varies tremendously, 100kT to few kT. + and – attract, but depends on solvent. Na+ Cl- = few kT (break up easily) 3. Hydrogen – few kT, up to 5kT 1. Hydrogen attached to a very electronegative elements, (O, N) causing the hydrogen to acquire a significant amount of positive charge. 2. Lone pair– electrons in relatively small space, very negative. Result is H is (+) and O is (-). Will bind to other molecules 4. Van der Waals –kT (weakest, but many of them together--significant). Two neutral atoms have instantaneous dipoles, and attract. Neon: -246°C; Xenon: 108°C www.chemguide.co.uk/atoms/bonding/hbond.html#top Covalent bonds holding bases together —very strong 3’ 5’ If add salt to solution, what is effect on melting Temp? Melting temp = Temp. at which DNA strands come apart. DNA double helix: Many weak (H-bonds), makes for very stable structure. If you have many weak bonds (e.g. each bond only few kT) you can get a biomolecule that will not fall apart. H bonded ~ -2 kT | | | | | | | | Say the unbound case has E= 0 | The bound case therefore has E = | 2kT. (Notice that the energy is | negative, i.e. it’s more stable if a | bond is formed) | | Zipped vs. unzipped What if just one bond? Bond/unbound? e2 ~ 8 What if 10 weak bonds? e 20 Many base pairs, essentially completely stable. We note that these numbers are completely unrealistic because our calculation doesn’t include the entropy. That is, it should be based on the free-energy (DG), not the energy, but the trend we see here, is still qualitatively correct. Still have end-fraying, but probability that whole thing comes apart– essentially zero. DNA RNA Proteins Central Dogma of Molecular Biology DNA: linear series of 4 nucleotides (bases): A,T,G,C Transcription [DNA & RNA similar] RNA: linear series of 4 nucleotides (bases): A,U,G,C Translation [RNA & Proteins different] Proteins: linear series of 20 amino acids: Met-Ala-Val-… each coded by 3 bases amino acid AUG Methionine; GCU Alanine; GUU Valine Proteins are 3-D strings of linear amino acids Do everything: structure, enzymes… http://learn.genetics.utah.edu/units/basics/transcribe/ DNA RNA Must uncoil the DNA, separate the strands, and use one of strands as a template to make a RNA strand. RNA: uses U instead of T, uses ribose instead of deoxyribose U U U The RNA that codes for proteins are called messenger RNA is an exact copy of DNA. RNA Proteins 3 nucleotides codes for 1 amino acid. Proteins are made up for a linear string of 20 different amino acids. Histidine U U Cysteine Glycine U Gene = sequence of DNA (or RNA) that makes a protein Also need to know where to start making the protein, and where to stop making the protein. If you can sequence all your DNA, how can you tell how many genes are there? Linear sequence of ~ 20 amino acids Can get enormous diversity and function with Proteins If 3 bases make a codon, how many amino acids might there be? Answer: 43 = 64 Have redundancy, typically in the last nucleotide The Central Dogma of Biology nucleus nucleus cytoplasm cytoplasm Each time a cell divides, entire DNA gets replicated. For us, that’s 3 billion base pairs. Splicing is fundamental for Gene Expression Splicing is fundamental for Gene Expression Alternative Splicing Adds Complexity 1 Gene, many proteins Down Syndrome Cell Adhesion Molecule DSCAM = 1 pre-mRNA = 38,000 potential mRNAs Now you understand why we’re not just a tiny worm. Why little worm (19,735 genes, 97 MB) has as many genes as a human (~21k, 3,000 MB = 3 GB)! A lot of “genes” are alternatively spliced, can produce more than one protein. Until very recently, used to call DNA which didn’t code for a protein “junk DNA” 1 mm____ Class evaluation 1. What was the most interesting thing you learned in class today? 2. What are you confused about? 3. Related to today’s subject, what would you like to know more about? 4. Any helpful comments. Answer, and turn in at the end of class.