Section 17.1. DNA

Section 17.1: DNA §Genetics – study of heredity §Artificial Selection – selective breeding or cross-pollination to produce desirable traits §Genes – unit of heredity §Chromosomes – repository of genetic information §Largest, most complex structure §Deoxyribonucleic acid (DNA) genetic information carrier Figure 17.1 The First Complete Structural Model of DNA §Molecular biology – deals elucidating structure & functional properties of genomes Section 17.1: DNA Figure 17.2 Two Models of DNA Structure 1. DNA directs the function of living cells and is transmitted to offspring §Double helix - two polydeoxynucleotide strands §Gene - DNA sequence containing base sequence information to code for a gene product, protein, or RNA §Genome - complete DNA base sequence of an organism §Replication - DNA synthesis involves complementary base pairing between the parental and newly synthesized strand Section 17.1: DNA 2. RNA synthesis – begins decoding process of genetic information Figure 17.3a An Overview of Genetic Information Flow §Transcription – information in a strand of DNA is copied into RNA molecules §Transcript – newly synthesized RNA moleule §Transcriptome - total RNA transcripts for an organism §mRNA, rRNA, tRNA Section 17.1: DNA 3. Translation – protein synthesis; decoding of mRNA by ribosome to produce polypeptide Figure 17.3b An Overview of Genetic Information Flow §mRNA - specifies the primary protein sequence §rRNA – location of protein synthesis §tRNA - delivers the specific amino acid §Proteome -entire set of proteins synthesized Section 17.1: DNA 4. Gene expression -control of timing of gene product synthesis in response to environmental or developmental cues §Transcription factors – regulate gene expression §Metabolome - sum total of low molecular weight metabolites produced by the cell Central dogma DNA RNA Protein Section 17.1: Nucleotide §Nitrogenous bases - derivatives of purine or pyrimidine, planar heterocyclic aromatic compounds §Common pyrimidines: thymine, cytosine, uracil §Common purines: adenine, guanine Section 17.1: Nucleotide Figure 14.25 Nucleoside Structure §Nucleoside -nitrogenous base linked via a glycosidic linkage to a pentose sugar §Ribose (e.g., adenosine) for RNA §Deoxyribose (e.g., deoxyadenosine) for DNA Section 17.1: DNA §Nucleotides - nucleosides with one or more phosphate groups §Most naturally occurring are 5′phosphate esters §Designation – A (adenine); G (guanine); C (cytosine), T (thymine), U (uracil) §Nucleic Acids – polymerization via 3’,5’-phosphodiester bonds §Join the 3′-hydroxyl of one nucleotide to the 5′-phosphate of another Figure 17.4 DNA Strand Structure Section 17.1: DNA Figure 17.5 DNA Structure §Primary structure - sequence of bases along pentosephosphodiester backbone §Base sequence read from 5’ to 3’ (5’-GCCATTTCCCG-3’) read à §a-double helix – two antiparallel strands wrapped around in right-hand manner §Base pairing: A-T; G –C §Hydrogen bonding: 3 G-C; 2 A-T Section 17.1: B-DNA Figure 17.6 DNA Structure: GC Base Pair Dimensions §Dimensions of B-DNA 1. One turn spans 3.32 nm; consists of 10.3 base pairs 2. Diameter is 2.37 nm, only suitable for base pairing a purine with a pyrimidine 3. Distance between adjacent base pairs is 0.29-0.30 nm Section 17.1: DNA §Stabilizing DNA 1. Hydrophobic interactions—internal base clustering 2. Hydrogen bonds—3 between CG base pairs; 2 between AT base pairs 3. Base stacking—bases are nearly planar and stacked, weak van der Waals forces between the rings 4. Hydration—water interacts with the structure of DNA 5. Electrostatic interactions—destabilization by negatively charged phosphates of sugar-phosphate backbone are minimized by the shielding effect of water on Mg2+ Section 17.1: DNA §DNA Structure: The Nature of Mutation §Mutations – small alterations to large chromosomal abnormalities §Most negative or neutral; rare positive mutations can enhance the adaptation of the organism §Raw material of evolution §Mutation rate low §Accuracy of DNA replication §Efficiency of DNA repair §Reduces error rate from 1/105 base pairs to 1/109 base pairs Section 17.1: Mutation types §Point mutations—small single base changes §Transition mutations - purine for purine or pyrimidine for pyrimidine substitutions §Transversion mutations - purine is substituted for a pyrimidine or vice versa §Single nucleotide polymorphisms (SNPs)- point mutations that occur in a population with some frequency §Classification if in coding portion: §Silent mutations have no discernable effect §Missense mutations have an observable effect §Nonsense mutations changes a codon for an amino acid to that of a premature stop codon Section 17.1: Mutation types §Indels - one to thousands of bases are inserted or removed §Frameshift mutation - Indels in coding region not divisible by three §Genome rearrangements can cause disruptions in gene structure or regulation. §Inversions - deleted DNA is reinserted into its original position in opposite orientation §Translocation - DNA fragment inserts else where in the genome §Duplication - creation of duplicate genes or parts of genes. §Causes of DNA Damage - exogenous and endogenous forces §Endogenous sources - tautomeric shifts, depurination, deamination, ROS-induced oxidative damage §Exogenous factors - radiation and xenobiotic exposure can also be mutagenic Section 17.1: DNA §DNA Structure: The Genetic Material §Watson and Crick – DNA structure in 1953 Figure 17.1 The First Complete Structural Model of DNA §Chemical structures/molecular dimensions of deoxyribose, nitrogenous bases, phosphate §Chemical analyses of base concentrations §A = T, C = G §Chargaff ’s rules - base pairing ü A pairs with T; C pairs with G on opposite strands §X-ray diffraction patterns §Symmetrical & helix – Rosalind Franklin §Diameter & pitch – Wilkins & Stokes §Linus Pauling - Proteins could exist in helical conformation Section 17.1: Other DNA §B-DNA §Physiological form §Right-handed helix, diameter 11Å §10 base pairs per turn (34Å) of helix §A-DNA §Right-handed helix, thicker than B-DNA §11 base pairs per turn of helix §Not found in vivo §Z-DNA Figure 17.10 A-DNA, B-DNA, and Z-DNA §Left-handed double helix §May play a role in gene expression Section 17.1: DNA Supercoiling §Linear and circular DNA can be in a relaxed or supercoiled shape §Two forms of supercoils §Toroidal – spiral §Plectonemic – coils wrapped around each other Figure 17.11 Linear and Circular DNA and DNA Winding Section 17.1: DNA Supercoiling §Negative supercoiling – linear underwound DNA is twisted left then sealed into a circle twists to right to relieve strain §Stores potential energy – facilitates stand separation §Positively supercoiling – linear overwound DNA is twisted right then sealed into a circle twists to left to relieve strain §Topoisomerases – relaxes supercoiling formed during strand separation §Make reversible cuts allowing supercoiled segments to unwind