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The Ghost in our Genes - From the Past via the Present to the Future11-06-03Madl0Pierre MADLDiv. of Material SciencesDep. Physics & BiophysicsUniversity of SalzburgHellbrunnerstr. 34A-5020 .ac.at/home.htm0

IntroNucleusCellOrganismPopulationIntro (1/4)Menu (Structural Levels):About myself: Genetics – A definition, Nucleus: Genetic code,Chromosomes, Cell: Replication, Transcription,Mitosis, Meiosis; Organism: Mendelian Genetics,Mutagenicity, Population: Epigenetics electronics engineer MSc in ecology PhD student part time service technicianDep. of Physics & Biophysics,Faculty of Natural Sciences07-10-29Madl11

IntroNucleusCellOrganismPopulationIntro (2/4)Genetics - A definition: . the study of genes . the study of heredity . the variation in living organismsWilliam Bateson (1861-1926) coined thename “genetics” in 190907-10-29Madl2Whether geneticists study at the molecular, cellular, organismal, familial, population, or evolutionarylevel, genes are always central to their studies.2

IntroNucleusCellOrganismPopulationIntro (3/4)Genetics - a fragmented science: Genomics Transcriptomics Proteomics Metabolomics07-10-29Madl3Genetics - a fragmented science: Genetics: study of genes at the molecular, cellular, organismal, familial, population, orevolutionary level. Transcriptomics: The need to look directly at the Proteins that are made. Fragments can be identified by referenceto the genome, if known, prediction. But needs powerful computers! BIOINFORMATICS Metabolomics: x3

IntroNucleusCellOrganismPopulationIntro (4/4)The central Dogma: DNA (transcription) RNA (translation) Proteins . a photocopyTomos D.,200607-10-29Madl4The central Dogma: a photocopy of the “recipe book” (genetic code) – every cell of a body has acomplete set of this code (holographic memory), only the environment determines which pagesof this code are read for the appropriate function (liver cell has to express liver-associatedfunction, proteins, etc, not muscle associated information). a specialized cell will only activate the appropriate information of this recipe book (i.e. chapterof the liver); a stem-cell can specialize into any cell – therefore is pluri-potential;Hologram:Top: This is how a photographic image would appear if you look at it withmagnifying glasses of increasing strength. If you were to cut away the pieces ofthe picture that are outside the frame shown, the pixels containing theinformation would be lost and the image could not be reconstructed.Below: This is the principle of information storage in the hologram. As mentionedbefore, the actual image would not be visible on the film, but the smallersections of the film still contain the information about the complete object. Ifyou cut it in half or even smaller pieces, you can still use each of the pieces tocreate a projection of the whole kitten (probably even with its ears intact - theyhave not been on the original photo used for the demonstration, so we will neverknow how they looked.).4

IntroNucleusCellOrganismPopulationGenetics on a “Nuclear” Level07-10-29Madl55

IntroNucleusCellCellOrganismPopulation(1/6)The EukaryoticCell: Plant Animal07-10-29Madl6Generalized features of higher plant and animal cells are:a. A plasma membrane encloses the cytoplasm in both.b. Plant cells have a rigid cell wall.c. In both, the nucleus contains DNA complexed with proteins and organized into chromosomes.d. The nuclear envelope is two layers of semipermeable membrane with pores that allowmovement of materials (e.g., ribosomes) between nucleoplasm and cytoplasm.e. The cytoplasm contains many materials and organelles. Important in genetics are:i. Centrioles (basal bodies) are in cytoplasm of nearly all animals, but not in most plants. Inanimals, a pair of centrioles is associated with the centrosome region of the cytoplasm wherespindle fibers are organized in mitosis or meiosis.ii. The endoplasmic reticulum (ER) is a double membrane system that runs through the cell. ERwith ribosomes attached collects proteins that will be secreted from the cell or localized to anorganelle.iii. Ribosomes synthesize proteins, either free in the cytoplasm or attached to the cytoplasmic sideof the ER.iv. Mitochondria are large organelles surrounded by double membrane that play a key role inenergy processing for the cell. They contain their own DNA encoding some mitochondrialproteins, rRNAs and tRNAs.v. Chloroplasts are photosynthetic structures that occur in plants. The organelle has a triplemembrane layer, and includes a genome encoding some of the genes needed for organellefunctions.6

IntroNucleusCellCellOrganismPopulation(2/6)The Genetic Code: DNA: double stranded es nuclear chromatin). RNA: single stranded macromolecule, spherical, intranuclearstructure(s)- nucleolus /nucleoli.07-10-29Madl7Nucleus: Genetic material of both eukaryotes and prokaryotes is DNA (deoxy-ribo-nucleic acid). Manyviruses also have DNA, but some have RNA (ribo-nucleic acid) genomes instead. DNA has two chains, each made of nucleotides composed of a deoxy-ribose sugar, a phosphategroup and a base. The chains form a double helix.7

IntroNucleusCellCellOrganismPopulation(3/6)The Genetic Code: Deoxyribose Phosphate 4 Bases:Adenine (Purine)Guanine (Purine)Cytosine (Pyrimidine)Thymine (Pyrimidine)Uracil (in RNA)07-10-29Madl8Genetic Code: Chromosome: ? A series of messages contained in the chromosomes; This code regulates cell functions by way of directing the synthesis of cell proteins; The code corresponds to the structure of the DNA; The code is transmitted to new cells during cell division;The basic unit is the nucleotide: it consists of a phosphate group deoxy-ribose sugarThere are two classes of nitrogenous bases:a. Purines (double-ring, nine-membered structures) include adenine (A) and guanine (G).b. Pyrimidines (one-ring, six-membered structures) include cytosine (C), thymine (T) in DNA anduracil (U) in RNA.The sequence of bases determines the genetic information. Genes are specific sequences ofnucleotides that pass traits from parents to offspring.8

IntroNucleusCellCellOrganismPopulation(4/6)The Genetic Code: Base pairingH-bonding Chargaff’s lawequal numbers of basesA & T;equal numbers of basesG & C;07-10-29Madl9The bases of the two strands are held together by hydrogen bonds between complementary bases(two for A-T pairs and three for G-C pairs). Individual H-bonds are relatively weak and so thestrands can be separated (by heating, for example). Complementary base pairing means that thesequence of one strand dictates the sequence of the other strand.Chargaff’s Law: 1st: In human DNA, for example, the four bases are present in these percentages: A 30.9% andT 29.4%; G 19.9% and C 19.8%. This strongly hinted towards the base pair makeup of theDNA, although Chargaff was not able to make this connection himself. 2nd: is that the composition of DNA varies from one species to another, in particular in therelative amounts of A, G, T, and C bases. Such evidence of molecular diversity, which had beenpresumed absent from DNA, made DNA a more credible candidate for the genetic material thanprotein.9

IntroNucleusCellCellOrganismPopulation(5/6)The Genetic Code: Code: AGCT (U) Backbone (PhosphateDeoxy-Ribose chain)07-10-29Madl10Deosyribose The base pairs are 0.34 nm apart, and one full turn of the DNA helix takes 3.4 nm, so there are 10 bp in acomplete turn. The diameter of a dsDNA helix is 2 nm. Because of the way the bases H-bond with each other, the opposite sugar-phosphate backbones are notequally spaced, resulting in a major and minor groove. This feature of DNA structure is important for proteinbinding.Genetic Code (sequence of AT & GC): Purines (double-ring, nine-membered structures) include adenine (A) and guanine (G). The code corresponds to the structure of the DNA and regulates cell functions by way ofdirecting the synthesis of cell proteins; The code is transmitted to new cells during cell division; The coded messages are contained in the chromosomes;10

IntroNucleusCellCellOrganismPopulation(6/6)What makes a Gene: Segments of the DNAstrings on chromosomeunique propertiesidentical in all cells(holographic properties) not all are expressed(biosemiotic principle) code for proteins andregulate other genes07-10-29Madl11Gene is the basic unit of inheritance and make proteins that make up nearly all we are (muscles, hair,eyes, etc.). By selecting different pieces of a gene, your body can make many kinds of proteins. Thisprocess is called alternative splicing.If a gene is “expressed” that means it is turned on and it will make proteins. xxx: Segments of the DNA chain; Xxx: beads on a (chromosome) string; Ccc: determine cell properties, both structure and functions unique to the cell;Genes are Identical in all cells (holographic aspect); not all genes are expressed in all cells; not all genes are active all the time; may code for enzymes or other functional proteins, structural proteins, regulators of other genes;almost everything that happens in our bodies happens because of proteins (walking, digestion,fighting disease). Locus: specific site of a gene on the chromosome. Since the chromosomes exist in pairs, genes arealso paired. Alleles: alternate forms of a gene can occupy the same locus (homo, hetero); Recessive gene: expressed only when homozygous; Dominant gene: homo or hetero or co-; Sex-linked gene: X, recessive, hemiHologram:Top: This is how a photographic image would appear if you look at it with magnifying glasses ofincreasing strength. If you were to cut away the pieces of the picture that are outside the frameshown, the pixels containing the information would be lost and the image could not be reconstructed.Below: This is the principle of information storage in the hologram. As mentioned before, the actual11

IntroNucleusCellOrganismPopulationD DNN AA iA-m Nol IMecul ATe/ Ipa Ock NingChromosome (1/12)Scaffolding: from DNA double helix to packed chromatin fiber to condensed chromosome07-10-29Madl12Eukaryotic chromosomes are linear dsDNA, and by weight contain about twice as much protein asDNA. The DNA-protein complex is called chromatin, and it is highly conserved in alleukaryotes.1. Both histones and non-histones are involved in physical structure of the chromosome.2. Histones are abundant, small proteins with a net ( ) charge. The five main types are H1, H2A,H2B, H3 and H4. By weight, chromosomes have equal amounts of DNA and histones.3. Histones are highly conserved between species (H1 less than the others).4. Non-histone is a general name for other proteins associated with DNA. This is a big group, withsome structural proteins, and some that bind only transiently. Non-histone proteins vary widely,even in different cells from the same organism. Most have a net (-) charge, and bind byattaching to histones. HMG (high mobility group) proteins are a well-studied example of nonhistone proteins.5. Chromatin formation involves histones, and condenses the DNA so it will fit into the cell.Chromatin formation has two components:a. Two molecules each of histones H2A, H2B, H3 and H4 associate to form a nucleosome core,and DNA wraps around it 1 3 4 times for a 7-fold condensation factor. Nucleosome cores areabout 11 nm in diameter.b. H1 serves as the linker histone, connecting nucleosomes to create chromatin with a diameter of30 nm, for an additional 6-fold condensation. The exact mechanism used by H1 is unknown.6. Chromatin is arranged in looped domains of DNA similar to those formed in prokaryoticchromosomes. Loops are anchored to the nuclear matrix at DNA sequences called MARs(matrix attachment regions). An average human chromosome has about 2,000 looped domains.Looped domains may be important in regulating transcription and replication.12