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Introduction to Molecular Genetics and Genomics

CHAPTERI ntroduction to MolecularGenetics andGenomics11 Inherited traits are affected by genes. Genes are composed of the chemical deoxyribonucleic acid(DNA). DNA replicates to form copies of itself that are identical(except for rare mutations). DNA contains a genetic code specifying what types ofenzymes and other proteins are made in cells. DNA occasionally mutates, and the mutant forms specifyaltered proteins that have reduced activity or stability. A mutant enzyme is an inborn error of metabolism thatblocks one step in a biochemical pathway for the metabolismof small molecules.

heritance and environmental factors. For example, weight is determined in part by inheritance but also in part by environ-ment: how much food we eat, its nutri-tional content, our exercise regimen, and so forth. Genetics is the study of biologically inherited traits, including traits …

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Transcription of Introduction to Molecular Genetics and Genomics

1 CHAPTERI ntroduction to MolecularGenetics andGenomics11 Inherited traits are affected by genes. Genes are composed of the chemical deoxyribonucleic acid(DNA). DNA replicates to form copies of itself that are identical(except for rare mutations). DNA contains a genetic code specifying what types ofenzymes and other proteins are made in cells. DNA occasionally mutates, and the mutant forms specifyaltered proteins that have reduced activity or stability. A mutant enzyme is an inborn error of metabolism thatblocks one step in a biochemical pathway for the metabolismof small molecules.

2 Traits are affected by environment as well as by genes. Organisms change genetically through generations in theprocess of biological MadnessAlfred D. Hershey and Martha Chase 1952 Independent Functions of Viral Protein and Nucleic Acid in Growth of BacteriophageThe Black Urine DiseaseArchibald E. Garrod 1908 Inborn Errors of MetabolismPRINCIPLESCONNECTIONSCHAPTER : The genetic MaterialExperimental Proof of the genetic Function of DNAG enetic Role of DNA in Structure: The Double Overview of DNA and ProteinsInborn Errors of Metabolism as a Cause of Hereditary DiseaseMutant Genes and Defective Expression: The Central DogmaTranscriptionTranslationThe genetic Folding and and.

3 From Genes to Genomes, fromProteins to ProteomesThe Molecular Unity of LifeNatural Selection and DiversityEach speciesof living organism has aunique set of inherited characteristicsthat makes it different from otherspecies. Each species has its own develop-mental plan often described as a sort of blueprint for building the organism which is encoded in the DNA molecules pre-sent in its cells. This developmental plandetermines the characteristics that are in-herited. Because organisms in the samespecies share the same developmental plan,organisms that are members of the samespecies usually resemble one another, al-though some notable exceptions usually aredifferences between males and females.

4 Forexample, it is easy to distinguish a humanbeing from a chimpanzee or a gorilla. A hu-man being habitually stands upright and haslong legs, relatively little body hair, a largebrain, and a flat face with a prominent nose,jutting chin, distinct lips, and small of these traits are inherited part of ourdevelopmental plan and help set us apartasHomo human beings are by no meansidentical. Many traits, or observable charac-teristics, differ from one person to is a great deal of variation in haircolor, eye color, skin color, height, weight,personality traits, and other human traits are transmitted biologi-cally, others culturally.

5 The color of oureyes results from biological inheritance, butthe native language we learned as a childresults from cultural inheritance. Manytraits are influenced jointly by biological in-heritance and environmental factors. Forexample, weight is determined in part byinheritance but also in part by environ-ment: how much food we eat, its nutri-tional content, our exercise regimen, and soforth. Geneticsis the study of biologicallyinherited traits, including traits that are in-fluenced in part by the fundamental concept of Genetics isthat:Inherited traits are determined by the ele-ments of heredity that are transmitted fromparents to offspring in reproduction; theseelements of heredity are called existence of genes and the rulesgoverning their transmission from gen-eration to generation were first articulatedby Gregor Mendel in 1866 (Chapter 3).

6 Mendel s formulation of inheritance was interms of the abstract rules by which heredi-tary elements (he called them factors ) aretransmitted from parents to offspring. Hisobjects of study were garden peas, withvariable traits like pea color and plantheight. At one time Genetics could be stud-ied only through the progeny producedfrom matings. genetic differences betweenspecies were impossible to define, becauseorganisms of different species usually do notmate, or they produce hybrid progeny thatdie or are sterile. This approach to the studyof Genetics is often referred to asclassicalge-netics, or organismic or morphological ge-netics.

7 Given the advances ofmolecular,ormodern, Genetics , it is possible to study dif-ferences between species through the com-parison and analysis of the DNA itself. Thereis no fundamental distinction between clas-sical and Molecular Genetics . They are dif-ferent and complementary ways of studyingthe same thing: the function of the geneticmaterial. In this book we include many ex-amples showing how Molecular and classi-cal Genetics can be used in combination toenhance the power of genetic foundation of Genetics as a molecu-lar science dates back to 1869, just threeyears after Mendel reported his exper-iments.

8 It was in 1869 that FriedrichMiescher discovered a new type of weakacid, abundant in the nuclei of white bloodcells. Miescher s weak acid turned out to bethe chemical substance we now call DNA(deoxyribonucleic acid).For many yearsthe biological function of DNA was un-known, and no role in heredity was as-cribed to it. This first section shows howDNA was eventually isolated and identifiedas the material that genes are made of. : The genetic MaterialThat the cell nucleus plays a key role in in-heritance was recognized in the 1870s bythe observation that the nuclei of male andfemale reproductive cells undergo fusion inthe process of fertilization.

9 Soon thereafter,chromosomeswere first observed insidethe nucleus as thread-like objects thatbecome visible in the light microscopewhen the cell is stained with certain were found to exhibit acharacteristic splitting behavior in whicheach daughter cell formed by cell division2 Chapter 1 Introduction to Molecular Genetics and Genomicsreceives an identical complement of chro-mosomes (Chapter 4). Further evidence forthe importance of chromosomes was pro-vided by the observation that, whereas thenumber of chromosomes in each cell maydiffer among biological species, the numberof chromosomes is nearly always constantwithin the cells of any particular features of chromosomes were wellunderstood by about 1900, and they madeit seem likely that chromosomes were thecarriers of the the 1920s.

10 Several lines of indirectevidence began to suggest a close relation-ship between chromosomes and studies with special stainsshowed that DNA is present in chromo-somes. Chromosomes also contain varioustypes of proteins, but the amount and kindsof chromosomal proteins differ greatly fromone cell type to another, whereas theamount of DNA per cell is , nearly all of the DNA presentin cells of higher organisms is present in thechromosomes. These arguments for DNA asthe genetic material were unconvincing,however, because crude chemical analyseshad suggested (erroneously, as it turnedout) that DNA lacks the chemical diversityneeded in a genetic substance.


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