CHAPTER 1 The Genetic Code of Genes and Genomes Genetics study of biologically inherited traits gene unit of heredity Genomics study of all the genes in an organism to understand their molecular organization function interaction and evolutionary history sequencing DNA constituents and learn how genes result in normal function or disease latest advance in molecular genetics When DNA is mutated it produces defective proteins which lead to inherited diseases Mendelian classical genetics genetics through analysis of offspring from matings Gregor Mendel discovered the existence of genes and rules governing their transmission Fridrich Misecher discovered DNA a weak acid abundant in the nuclei of WBC in 1869 1 1 DNA is the molecule of heredity In 1870 nuclei of reproductive cells were observed to fuse in fertilization Chromosomes thread like objects inside nucleus exhibit splitting behavior by 1920s evidence of relationship between chromosomes and DNA is apparent DNA is discovered in chromosomes but so is protein and although DNA is constant in type and amount per cell it is not as chemically diverse as protein Experiments now had to prove DNA is the genetic material and proteins are not Genetic traits can be altered by treatment with pure DNA Streptococcus pneumoniae provides capsule around bacterium protecting it forming a large colony with a smooth S appearance Strains of strep that cannot synthesize the capsule form small colonies with a rough R surface do not cause pneumonia because bacteria are inactivated by host In 1928 Frederick Griffith showed that mice injected with heat killed S cells and R cells die Injected material from dead S cells can enter living R cells and synthesize capsule R bacteria undergo transformation into S bacteria In 1944 Oswald Avery Colin MacLeod and Macyln McCarty showed the substance causing the transformation of R cells to S cells was DNA Experiment determined that the material was not protein or RNA Transmission of DNA is the link between generations In 1952 Alfred Hershey and Martha Chase studied E coli after infection by virus T2 A bacteriophage or phage is a virus that arracks bacterial cells DNA contains phosphorus but not sulfur and protein contains sulfur but not phosphorus so Hersey and Chase deduced that the genetic material in T2 phage is DNA by injecting E coli cells and seeing which labels survived 1 2 The structure of DNA is a double helix with two intertwined strands A central feature of double stranded DNA is complementary base pairing In 1953 first 3D structure of the DNA molecule proposed by James Watson and Francis Crick Nothing restricts the sequence of bases in a single strand so any sequence could be present along one strand Complementary base pairing is also known as Watson Crick base pairing Each DNA strand has a polarity directionality determined by the direction the nucleotide is pointing 5 end trunk 3 end tail antiparallel oppositely oriented strands In replication each parental DNA strand directs the synthesis of a new partner strand 1 3 Genes affect organism through the action of proteins Genes exert their effects on organisms indirectly Proteins control the chemical and physical processes of cells known as metabolism Many proteins are enzymes catalysts that accelerate biochemical reactions Enzymes are essential for the breakdown of organic molecules generating the chemical energy needed for cellular activities synthesis of small molecules and assembly into larger ones Archibald Garrod determined that an inherited defect in metabolism results from an inherited defect in an enzyme Hereditary diseases are inborn errors of metabolism Ex In alkaptonuria homogentisic acid is the abnormal substance excreted black urine disease Garrod proposed that homogentisic acid comes from breakdown of two amino acids phenylalanine and tyrosine Any sequence of biochemical reactions is called a biochemical pathway or metabolic pathway Persons with an inborn error of metabolism have a defect in one step of a metabolic pathway because they lack a functional enzyme block at that step of the pathway In a block the substrate of the defective enzyme typically accumulates Phenylketonuria PKU results from a defect in the enzyme phenylalanine hydroxylase PAH Excess phenylalanine from this defect breaks down into harmful metabolites that cause defects in myelin formation damaging the nervous system and leading to severe mental retardation A defective enzyme results from a mutant gene Genetic analysis led to the one gene one enzyme hypothesis In the 1940s George W Beadle and Edward L Tatum connected genes with enzymes using genetic analysis linking genetics and biochemistry A minimal medium contains only the nutrients that are essential for growth of the organism Isolation of a set of mutants affecting a biological process like metabolism is a mutant screen If a strain with a mutant enzyme that blocks a particular step in a linear metabolic pathway can grow when an intermediate is added to the growth medium it means that the location of the intermediate in the pathway is downstream of the enzymatic step that is blocked Mutant screens sometimes isolate different mutations in the same gene Mutations that have defects in the same gene are identified by means of a complementation test where two mutations are brought together into the same cell usually done in organisms with one set of chromosomes otherwise mating can be used physical contact of filaments This test forms a heterokaryon a hybrid filament containing mutant forms of both genes When a heterokaryon grows in a minimal medium it undergoes complementation meaning the mutations are in different genes When a heterokaryon fails to grow in a minimal medium this is noncomplementation meaning the two mutations are in the same gene A complementation test brings two mutant genes together in the same cell or organism If this cell or organism is nonmutant the mutations are said to complement one another and it means that the parental strains have mutations in different genes If the cell or organism is mutant the mutations fail to complement one another and it means that the parental mutations are in the same gene A complementation test identifies mutations in the same gene A gene is a set of mutations that make up a single complementation group or a group of non complementing mutations Any pair of mutations within a complementation group fails to complement one another Beadle and Tatum s experiments were