Chapter 1 IntroductionBranches of Genetics1. Transmission genetics• Classical or Mendelian genetics2. Molecular genetics– chromosomes, DNA, regulation of gene expression– recombinant DNA, biotechnology, bioinformatics, genomics, proteomics3. Population, evolutionary genetics• allelic frequencies in populations• effects of migration• study relatedness of taxa via DNA and protein analysis4. Quantitative genetics– effects of many genesWhat is a gene?• A unit of inheritance• A specific location on a chromosome• A sequence of base pairs• Transcribed into mRNA• Encodes a protein• Expressed • The specifier of a phenotype• Composed of DNAModel Organismscheap to growshort generation timecan control matingno ethical concernsmany offspringsome have simpler systemssmall (most)(humans?)Why use model organisms?• Development• Disease• Metabolic pathways (biochemistry)• Evolution• All living organisms share a common descentProkaryotic model organismBacteria E. coli1. Unicellular– Saccharomyces cerevisiae• Bakers yeast– Chlamydomonas reinhardtii• Green algaeEukaryotic model organism2. MulticellularNeurospora crassa– Orange bread moldC. elegans– Nematode worm– 1mm long, 959 cells, transparentXenopus laevisbig eggsZebra daniotransparent developmenthttp://www.biology.uiowa.edu/faculty_info.php?ID=1120Arabidopsis thaliana– small plant/mustard familyDrosophila melanogaster– Fruit flyMus musculusDNA Chapter 2 – read principal pointsDeoxyribonucleic acid• Functional Properties1. Replication – DNA is copied prior to cell division why?2. Storage of information DNA inherited• from parent to offspring• from cell to cell– Gene expression – Genes encode proteins3. Mutation – DNA changes to allow variation and adaptation, the basis of evolutionA six-legged green frog. (Reproduced by permission of JLM Visuals http://www.isogenic.info/assets/images/autogen/a_image16.jpghttp://3quarksdaily.blogs.com/3quarksdaily/images/wolfe_seal_1.jpgNeutral, harmful, adaptive?DNA History1869 Meischer extracted nuclein from pus1900s – chromosomes discoveredThe genetic material must have the 3 functional propertiesGriffith finds “transforming factor”1928 London• Streptococcus pneumoniae bacterium • pneumonia in mice, deadly to humanssputum with bacteria• Smooth strain (IIIS) – virulent– polysaccharide capsule– capsule allows bacteria to evade immune systemisolate live IIISfrom mouseS pneumococcus kills mouse in 24 hours. But 100 million IIR strain bacterial cells is harmless S R(Research photographs of Dr. Harriet Ephrussi-Taylor, courtesy of The Rockefeller University.)Appearance when grown on an agar plate• Rough strain IIR is avirulentIIR lacks capsule-> isolate live IIRThe experiment:• Heat kill IIIS strain  mouse ?Heat killed IIIS strain + live strain IIR mouse ?Which strain is isolated?Griffith’s experiment and conclusionA “transforming factor” in killed S strain transformed live R strain into SDNA or protein?1944 Avery, McCarty, Macleod1. Heat kill IIIS2. Remove lipids and sugars – how?3. Divide into 3 and treat with: proteaseRNaseDNase next, add live R cells to each1952 Hershey and ChaseUsed T2 bacteriophage + E. coliA phage is a virus that infects bacteriaHow phage work1. phage adsorbs onto bacterial surface2. Genetic material injected3. Cell makes progeny phageIS the genetic material DNA, or protein?Experiment1. Label phage protein with 35S  infect E. coli  strip phage off cell surface• New phage are not radioactive2. Label phage DNA with 32P -> infect E.coli -> blend ->• New phage contain 32PHershey and Chase conclusionDNA is responsible for function and reproduction of phage virus = the genetic materialStructure of DNA = nucleotide polymersNUCLEOTIDES1. Nitrogenous base• Purines = guanine and adenineG AHow big IS a nucleotide? UTAH cell scalePyrimidinesThymine TCytosine CRNA contains uracil U2. Deoxyribose sugarRNA (ribose) 2’ OH makes RNA less stable than DNA Sugar + base = nucleoside3. Phosphate (PO4)Nucleotide = base + sugar + phosphateDNA is a polymer of nucleotidespolarity 5’carbon to 3’hydroxylDNA (double helix)Watson and Crick 1953 X-ray diffraction data RosalindFranklin, Maurice WilkinsGETncm/justsaycust-recrate-itemcommunittg/stores/dtg/stores/d-favorite-listruejust-say-no• DNA properties include:Complementary base pairing1. Hydrogen bonds between complementary basesHow many bonds in a G-C pair?A-T?Which is stronger?Complementary base pairsWhich are the G-Cpairs?2. 2 antiparallel stands5’  3’ and 3’  5’3. . Sugar phosphate backbones4. Base compositionDNA 50% purine 50% pyrimidineA = T G = C A/T = 1 C/G = 1A +T does not equal C+GA + G = C + TChargaff (1950)5. DNA can denature and renature• Melt hydrogen bonds (chemical or heat)And5. Right handed helix6. Complete turn of the helix is 0.34 nm, 10 bases per turn7. Major and minor groovesMajor and minor groovesForms of DNAB DNA right helix10 bp/ turnA DNA right helix10.9 bp/ turnZ DNA left helix12 bp/turn (role?)Ethanol water 4MNaClDehydrated hydratedCellular DNA closest to B DNA10.4 bp/turnReplication of DNA by Complementary Base PairingHHMI interactive DNA replication advancedOrganization of DNA in chromosomes• Genome– Full amount of genetic material in a single cellInfluenza ssRNA HIV ssRNABacteriophageds DNAViral chromosomeSingle or double stranded DNA or RNACircular or linearHerpes ds DNAParvovirus ssDNAGenetic material in prokaryotes• 1 (usually) chromosome• Circular (most) chromosome • Supercoiled DNA located in nucleoid regionNeisseria gonorrhoeaeE. coli = 4.6 million bp, circular chromosome1500 um genome stuffed into a 1 um cell via supercoilingE. coli cells E. coli DNA• Supercoiling and topoisomerases in E. coli bacterial cell• Some bacteria contain extra-chromosomal DNA called a plasmidEukaryotic ChromosomesC value - Amount of DNA varies among speciesThe structure of chromatin• DNA + proteins• Highly conservedEukaryotic chromosomesIn man, the DNA molecule in a diploid cell, if fully extended, would have a length of ~2 meters. If you unwrap all the DNA you have in all your cells, you could reach the moon ...6000 times.This 2 meters is stuffed into a 50um cell!Histones and non-histonesHistone proteins basicnet + charge interacts with – charged DNAPackage DNAHighly conservedNon-histone proteinsvary among