11 1 How Did Scientists Discover That Genes Are Made of DNA Late 1800s scientists had a limited knowledge of genes Chromosomes are made of deoxyribonucleic acid DNA and protein Genes are parts of structures called chromosomes Heritable information is carried in discrete units called genes They did not know what genes were made of 1868 Miescher investigated the chemical composition of the nucleus Isolated an organic acid that was high in phosphorus Called it nuclein We call it DNA deoxyribonucleic acid today Exactly how information was passed from one individual to the next was not understood This led to several critical and significant scientific experiments Transformed bacteria revealed the link between genes and DNA 1928 Griffith s lab was working to develop a vaccine for pneumonia Isolated 2 strains of Streptococcus pneumoniae bacteria S strain smooth appearance pathogenic caused pneumonia when injected into mice killing them R strain rough appearance non pathogenic did not cause pneumonia when injected into mice When the S strain was heat killed and injected into mice it did NOT cause pneumonia Griffith made a sample of heat killed S strain and mixed it with the living R strain Injection of the combination into mice caused pneumonia and death This was unexpected since neither element alone caused the disease The results of Griffith s experiments led to several new deductions about the genetic Something changed the living harmless R strain into the deadly S strain But How Griffith called this process TRANSFORMATION The substance that caused this transformation might be the long sought molecule of The transforming molecule is DNA 1933 Alloway s lab showed that transformation occurred just as readily in culture dishes material heredity in vitro This showed that the mouse itself in Griffith s experiments was not involved in the transformation So what exactly was the material transforming cells then 1940s Avery MacLeod McCarty lab isolated DNA from S strain bacteria mixed it with live R strain bacteria and produced live S strain bacteria This suggested that the transforming molecule from the S strain was DNA To verify this two new experiments designed Cell extracts treated with protein digesting enzymes could still transform Cell extracts treated with DNA digesting enzymes lost their transforming bacteria ability Concluded that DNA not protein transforms bacteria Griffith s experiments can be explained if DNA is the transforming agent Heating S strain cells killed them but did not completely destroy their DNA When killed S strain bacteria were mixed with living R strain bacteria fragments of DNA from the dead S strain cells became incorporated into the chromosome of the R strain bacteria If these fragments of DNA contained the genes needed to cause disease an R strain cell would be transformed into an S strain cell Thus Avery MacLeod McCarty concluded that genes are made of DNA Bacteriophages Viruses that infect bacteria Consist of protein coat and DNA core Experiment examined what was transforming part protein or DNA 1950s Hershey Chase created radioactively labeled bacteriophages to follow that Inject their hereditary material into bacteria transformation process on a finer detail Radioactive sulfur S35 labeled proteins Radioactive phosphorus P32 labeled DNA Allowed labeled viruses to infect bacteria Asked Where are the radioactive labels after infection Inside or outside cell The answer would determine what the material was that did the transforming Hershey and Chase results DNA and not protein was transforming the bacterial cells 11 2 What Is the Structure of DNA The secrets of DNA function and therefore of heredity itself are found in the 3 D structure of the DNA molecule DNA is composed of four nucleotides Each nucleotide has three components 1 A phosphate group 2 A deoxyribose sugar 3 One of four nitrogen containing bases Thymine T Cytosine C Adenine A and Guanine G DNA is a double helix of two nucleotide strands Hydrogen bonds between complementary bases hold two DNA strands together A G called PURINES double ringed structures C T called PYRIMIDINES single ringed structures 1940s Chargaff determined that nucleotides were present in specific ratios in double stranded DNA molecules 1 Adenine always equaled thymine A T 2 Guanine always equaled cytosine G C 3 This finding was called Chargaff s rule If an organism has a 22 cytosine content what percent A T and G do they have Based on your knowledge of CHARGRAFF s rule answer this C 22 A T G 1940s Franklin Wilkins studied the structure of DNA crystals using X ray diffraction patterns 1 They deduced several qualities of DNA It is long and thin It has a uniform diameter of 2 nanometers It is helical twisting like a corkscrew and consisting of repeating subunits 1953 Watson Crick combined the X ray data with bonding theory to deduce DNA structure DNA is made of two strands of nucleotides Within each DNA strand the phosphate group of one nucleotide bonds to the sugar of the next nucleotide in the same strand The deoxyribose and phosphate portions make up the sugar phosphate backbone Nucleotide bases protrude from this backbone The two strands run anti parallel to each other one going 5 3 and the other 3 Hydrogen bonds between complementary bases hold two DNA strands together in a double helix 1 The bases protrude inward toward each other from the sugar phosphate backbone like 2 Hydrogen bonds hold the base pairs together like steps on the ladder 3 The ladder like structure is twisted into a double helix 4 The two strands in a DNA double helix are said to be anti parallel oriented in opposite Hydrogen bonds between complementary bases hold two DNA strands together continued 1 Bases that bond with each other are called complementary base pairs 2 Complementary base pairing explains Chargaff s rule where A T and G C 3 Since every A is paired with T no matter how many As are present there will be an equal 5 rungs on a ladder directions number of Ts 4 A G are larger purines double ringed T C are smaller pyrimidines single ringed 5 Because base pairing always places a large molecule with a small one the diameter of the double helix remains constant Hydrogen bonds between complementary bases hold two DNA strands together continued 11 3 How Does DNA Encode Information How can a molecule with only four simple parts be the carrier of genetic information The key lies in the sequence not the number of subunits Within a DNA strand the four
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