CHAPTER 18 SOLVE IT Counting mRNAs 533 CYTOPLASMIC CONTROL OF MESSENGER RNA STABILITY 533 Regulation of Gene Expression Induction of Transcriptional Activity by Environmental and Biological Factors 534 in Prokaryotes 504 TEMPERATURE:THE HEAT-SHOCK GENES 535 D'Herelle's Dream of Treating Dysentery in SIGNAL MOLECULES:GENES THAT RESPOND TO Humans by Phage Therapy 504 HORMONES 535 Constitutive,Inducible,and Repressible Gene Molecular Control of Transcription in Expression 506 Eukaryotes 537 Positive and Negative Control of Gene DNA SEQUENCES INVOLVED IN THE CONTROL OF Expression 507 TRANSCRIPTION 537 PROTEINS INVOLVED IN THE CONTROL OF TRANSCRIPTION: Operons:Coordinately Regulated Units of TRANSCRIPTION FACTORS 538 Gene Expression 509 PROBLEM-SOLVING SKILLS Defining the The Lactose Operon in E.coli:Induction and Sequences Required for a Gene's Expression 539 Catabolite Repression 511 Posttranscriptional Regulation of Gene INDUCTION 513 Expression by RNA Interference 541 SOLVE IT Constitutive Mutations in the E.coli lac RNAi PATHWAYS 541 Operon 513 SOURCES OF SHORT INTERFERING RNAs AND MicroRNAs 543 CATABOLITE REPRESSION 514 Gene Expression and Chromatin PROBLEM SOLVING SKILLS Testing Your Organization 544 Understanding of the lac Operon 516 SOLVE IT Using RNAi in Cell Research 545 PROTEIN-DNA INTERACTIONS THAT CONTROL TRANSCRIPTION OF THE LAC OPERON 517 EUCHROMATIN AND HETEROCHROMATIN 545 MOLECULAR ORGANIZATION OF TRANSCRIPTIONALLY ACTIVE The Tryptophan Operon in E.coli:Repression DNA 545 and Attenuation 519 CHROMATIN REMODELING 546 REPRESSION 519 DNA METHYLATION 547 ATTENUATION 520 IMPRINTING 548 SOLVE IT Regulation of the Histidine Operon of ON THE CUTTING EDGE The Epigenetics of Twins 549 Salmonella typhimurium 522 Activation and Inactivation of Whole ON THE CUTTING EDGE The Lysine Riboswitch 524 Chromosomes 550 Translational Control of Gene Expression 525 INACTIVATION OF X CHROMOSOMES IN MAMMALS 551 Posttranslational Regulatory HYPERACTIVATION OF X CHROMOSOMES IN DROSOPHILA 552 Mechanisms 526 HYPOACTIVATION OF X CHROMOSOMES IN CAENORHABDITIS 553 CHAPTER 1 CHAPTER 20 Regulation of Gene Expression The Genetic Control of Animal in Eukaryotes 531 Development 558 African Trypanosomes:A Wardrobe of Molecular Disguises 531 Stem-Cell Therapy 558 Ways of Regulating Eukaryotic Gene A Genetic Perspective on Development 559 Expression:An Overview 532 Maternal Gene Activity in Development 561 DIMENSIONS OF EUKARYOTIC GENE REGULATION 532 MATERNAL-EFFECT GENES 561 CONTROLLED TRANSCRIPTION OF DNA 532 SOLVE IT A Maternal-Effect Mutation in the cinnamon ALTERNATE SPLICING OF RNA 533 Gene 562 xvi
xvi CHAPTER 1 8 Regulation of Gene Expression in Prokaryotes 504 D’Hérelle’s Dream of Treating Dysentery in Humans by Phage Therapy 504 Constitutive, Inducible, and Repressible Gene Expression 506 Positive and Negative Control of Gene Expression 507 Operons: Coordinately Regulated Units of Gene Expression 509 The Lactose Operon in E. coli: Induction and Catabolite Repression 511 INDUCTION 513 SOLVE IT Constitutive Mutations in the E. coli lac Operon 513 CATABOLITE REPRESSION 514 PROBLEM SOLVING SKILLS Testing Your Understanding of the lac Operon 516 PROTEIN-DNA INTERACTIONS THAT CONTROL TRANSCRIPTION OF THE LAC OPERON 517 The Tryptophan Operon in E. coli: Repression and Attenuation 519 REPRESSION 519 ATTENUATION 520 SOLVE IT Regulation of the Histidine Operon of Salmonella typhimurium 522 ON THE CUTTING EDGE The Lysine Riboswitch 524 Translational Control of Gene Expression 525 Posttranslational Regulatory Mechanisms 526 CHAPTER 1 9 Regulation of Gene Expression in Eukaryotes 531 African Trypanosomes: A Wardrobe of Molecular Disguises 531 Ways of Regulating Eukaryotic Gene Expression: An Overview 532 DIMENSIONS OF EUKARYOTIC GENE REGULATION 532 CONTROLLED TRANSCRIPTION OF DNA 532 ALTERNATE SPLICING OF RNA 533 SOLVE IT Counting mRNAs 533 CYTOPLASMIC CONTROL OF MESSENGER RNA STABILITY 533 Induction of Transcriptional Activity by Environmental and Biological Factors 534 TEMPERATURE: THE HEAT-SHOCK GENES 535 SIGNAL MOLECULES: GENES THAT RESPOND TO HORMONES 535 Molecular Control of Transcription in Eukaryotes 537 DNA SEQUENCES INVOLVED IN THE CONTROL OF TRANSCRIPTION 537 PROTEINS INVOLVED IN THE CONTROL OF TRANSCRIPTION: TRANSCRIPTION FACTORS 538 PROBLEM-SOLVING SKILLS Defining the Sequences Required for a Gene’s Expression 539 Posttranscriptional Regulation of Gene Expression by RNA Interference 541 RNAi PATHWAYS 541 SOURCES OF SHORT INTERFERING RNAs AND MicroRNAs 543 Gene Expression and Chromatin Organization 544 SOLVE IT Using RNAi in Cell Research 545 EUCHROMATIN AND HETEROCHROMATIN 545 MOLECULAR ORGANIZATION OF TRANSCRIPTIONALLY ACTIVE DNA 545 CHROMATIN REMODELING 546 DNA METHYLATION 547 IMPRINTING 548 ON THE CUTTING EDGE The Epigenetics of Twins 549 Activation and Inactivation of Whole Chromosomes 550 INACTIVATION OF X CHROMOSOMES IN MAMMALS 551 HYPERACTIVATION OF X CHROMOSOMES IN DROSOPHILA 552 HYPOACTIVATION OF X CHROMOSOMES IN CAENORHABDITIS 553 CHAPTER 2 0 The Genetic Control of Animal Development 558 Stem-Cell Therapy 558 A Genetic Perspective on Development 559 Maternal Gene Activity in Development 561 MATERNAL-EFFECT GENES 561 SOLVE IT A Maternal-Effect Mutation in the cinnamon Gene 562
DETERMINATION OF THE DORSAL-VENTRAL phMSH2 598 AND ANTERIOR-POSTERIOR AXES 562 pBRCA1 and pBRCA2 599 Zygotic Gene Activity in Development 565 FOCUS ON Cancer and Genetic Counseling 600 BODY SEGMENTATION 565 Genetic Pathways to Cancer 600 ORGAN FORMATION 567 SPECIFICATION OF CELL TYPES 569 SOLVE IT Cave Blindness 569 PROBLEM-SOLVING SKILLS The Effects of Mutations during Eye Development 571 CHAPTER 22 Genetic Analysis of Development in Vertebrates 571 Inheritance of Complex VERTEBRATE HOMOLOGUES OF INVERTEBRATE GENES 571 Traits 607 THE MOUSE:RANDOM INSERTION MUTATIONS AND Cardiovascular Disease:A Combination of GENE-SPECIFIC KNOCKOUT MUTATIONS 572 Genetic and Environmental Factors 607 STUDIES WITH MAMMALIAN STEM CELLS 573 Complex Traits 608 REPRODUCTIVE CLONING 574 GENETIC CHANGES IN THE DIFFERENTIATION OF VERTEBRATE QUANTIFYING COMPLEX TRAITS 608 IMMUNE CELLS 575 GENETIC AND ENVIRONMENTAL FACTORS INFLUENCE QUANTITATIVE TRAITS 608 MULTIPLE GENES INFLUENCE QUANTITATIVE TRAITS 608 THRESHOLD TRAITS 610 CHAPTER 21 Statistics of Quantitative Genetics 611 The Genetic Basis of Cancer 581 FREQUENCY DISTRIBUTIONS 611 THE MEAN AND THE MODAL CLASS 612 A Molecular Family Connection 581 THE VARIANCE AND THE STANDARD DEVIATION 612 Cancer:A Genetic Disease 582 Analysis of Quantitative Traits 613 THE MANY FORMS OF CANCER 582 THE MULTIPLE FACTOR HYPOTHESIS 614 CANCER AND THE CELL CYCLE 583 PARTITIONING THE PHENOTYPIC VARIANCE 614 CANCER AND PROGRAMMED CELL DEATH 584 SOLVE IT Estimating Genetic and Environmental A GENETIC BASIS FOR CANCER 584 Variance Components 615 Oncogenes 585 BROAD-SENSE HERITABILITY 615 TUMOR-INDUCING RETROVIRUSES AND VIRAL NARROW-SENSE HERITABILITY 616 ONCOGENES 585 PREDICTING PHENOTYPES 617 SOLVE IT The v-erbB and v-fms Viral SOLVE IT Using the Narrow-Sense Oncogenes 586 Heritability 618 CELLULAR HOMOLOGUES OF VIRAL ONCOGENES: ARTIFICIAL SELECTION 618 THE PROTO-ONCOGENES 586 MUTANT CELLULAR ONCOGENES AND CANCER 587 FOCUS ON Artificial Selection 619 CHROMOSOME REARRANGEMENTS AND CANCER 589 QUANTITATIVE TRAIT LOCI 620 Tumor Suppressor Genes 590 PROBLEM-SOLVING SKILLS Detecting Dominance at a QTL 623 INHERITED CANCERS AND KNUDSON'S TWO-HIT HYPOTHESIS 590 Correlations Between Relatives 624 PROBLEM-SOLVING SKILLS Estimating Mutation CORRELATING QUANTITATIVE PHENOTYPES BETWEEN Rates in Retinoblastoma 593 RELATIVES 625 CELLULAR ROLES OF TUMOR SUPPRESSOR PROTEINS 593 INTERPRETING CORRELATIONS BETWEEN RELATIVES 626 pRB 593 Quantitative Genetics of Human Behavioral p53595 Traits 628 SOLVE IT Downstream of p53 595 INTELLIGENCE 628 pAPC 597 PERSONALITY 629 xvii
xvii DETERMINATION OF THE DORSAL–VENTRAL AND ANTERIOR–POSTERIOR AXES 562 Zygotic Gene Activity in Development 565 BODY SEGMENTATION 565 ORGAN FORMATION 567 SPECIFICATION OF CELL TYPES 569 SOLVE IT Cave Blindness 569 PROBLEM-SOLVING SKILLS The Effects of Mutations during Eye Development 571 Genetic Analysis of Development in Vertebrates 571 VERTEBRATE HOMOLOGUES OF INVERTEBRATE GENES 571 THE MOUSE: RANDOM INSERTION MUTATIONS AND GENE-SPECIFIC KNOCKOUT MUTATIONS 572 STUDIES WITH MAMMALIAN STEM CELLS 573 REPRODUCTIVE CLONING 574 GENETIC CHANGES IN THE DIFFERENTIATION OF VERTEBRATE IMMUNE CELLS 575 CHAPTER 2 1 The Genetic Basis of Cancer 581 A Molecular Family Connection 581 Cancer: A Genetic Disease 582 THE MANY FORMS OF CANCER 582 CANCER AND THE CELL CYCLE 583 CANCER AND PROGRAMMED CELL DEATH 584 A GENETIC BASIS FOR CANCER 584 Oncogenes 585 TUMOR-INDUCING RETROVIRUSES AND VIRAL ONCOGENES 585 SOLVE IT The v-erbB and v-fms Viral Oncogenes 586 CELLULAR HOMOLOGUES OF VIRAL ONCOGENES: THE PROTO-ONCOGENES 586 MUTANT CELLULAR ONCOGENES AND CANCER 587 CHROMOSOME REARRANGEMENTS AND CANCER 589 Tumor Suppressor Genes 590 INHERITED CANCERS AND KNUDSON’S TWO-HIT HYPOTHESIS 590 PROBLEM-SOLVING SKILLS Estimating Mutation Rates in Retinoblastoma 593 CELLULAR ROLES OF TUMOR SUPPRESSOR PROTEINS 593 pRB 593 p53 595 SOLVE IT Downstream of p53 595 pAPC 597 phMSH2 598 pBRCA1 and pBRCA2 599 FOCUS ON Cancer and Genetic Counseling 600 Genetic Pathways to Cancer 600 CHAPTER 2 2 Inheritance of Complex Traits 607 Cardiovascular Disease: A Combination of Genetic and Environmental Factors 607 Complex Traits 608 QUANTIFYING COMPLEX TRAITS 608 GENETIC AND ENVIRONMENTAL FACTORS INFLUENCE QUANTITATIVE TRAITS 608 MULTIPLE GENES INFLUENCE QUANTITATIVE TRAITS 608 THRESHOLD TRAITS 610 Statistics of Quantitative Genetics 611 FREQUENCY DISTRIBUTIONS 611 THE MEAN AND THE MODAL CLASS 612 THE VARIANCE AND THE STANDARD DEVIATION 612 Analysis of Quantitative Traits 613 THE MULTIPLE FACTOR HYPOTHESIS 614 PARTITIONING THE PHENOTYPIC VARIANCE 614 SOLVE IT Estimating Genetic and Environmental Variance Components 615 BROAD-SENSE HERITABILITY 615 NARROW-SENSE HERITABILITY 616 PREDICTING PHENOTYPES 617 SOLVE IT Using the Narrow-Sense Heritability 618 ARTIFICIAL SELECTION 618 FOCUS ON Artificial Selection 619 QUANTITATIVE TRAIT LOCI 620 PROBLEM-SOLVING SKILLS Detecting Dominance at a QTL 623 Correlations Between Relatives 624 CORRELATING QUANTITATIVE PHENOTYPES BETWEEN RELATIVES 625 INTERPRETING CORRELATIONS BETWEEN RELATIVES 626 Quantitative Genetics of Human Behavioral Traits 628 INTELLIGENCE 628 PERSONALITY 629
CHAPTER 23 VARIATION IN PROTEIN STRUCTURE 661 VARIATION IN NUCLEOTIDE SEQUENCES 661 Population Genetics 634 Molecular Evolution 662 MOLECULES AS "DOCUMENTS OF EVOLUTIONARY A Remote Colony 634 HISTORY"663 The Theory of Allele Frequencies 635 MOLECULAR PHYLOGENIES 664 ESTIMATING ALLELE FREQUENCIES 635 RATES OF MOLECULAR EVOLUTION 664 RELATING GENOTYPE FREQUENCIES TO ALLELE PROBLEM-SOLVING SKILLS Using Mitochondrial FREQUENCIES:THE HARDY-WEINBERG PRINCIPLE 636 DNA to Establish a Phylogeny 665 APPLICATIONS OF THE HARDY-WEINBERG PRINCIPLE 636 THE MOLECULAR CLOCK 667 EXCEPTIONS TO THE HARDY-WEINBERG PRINCIPLE 638 SOLVE IT Calculating Divergence Times 667 SOLVE IT The Effects of Inbreeding on Hardy- VARIATION IN THE EVOLUTION OF PROTEIN SEQUENCES 667 Weinberg Frequencies 639 VARIATION IN THE EVOLUTION OF DNA SEQUENCES 668 USING ALLELE FREQUENCIES IN GENETIC COUNSELING 640 THE NEUTRAL THEORY OF MOLECULAR EVOLUTION 669 Natural Selection 641 SOLVE IT Evolution by Mutation and Genetic THE CONCEPT OF FITNESS 641 Drift 670 NATURAL SELECTION AT THE LEVEL OF THE GENE 642 MOLECULAR EVOLUTION AND PHENOTYPIC EVOLUTION 670 SOLVE IT Selection Against a Harmful Recessive Speciation 672 Allele 643 WHAT IS A SPECIES?672 Random Genetic Drift 645 MODES OF SPECIATION 674 RANDOM CHANGES IN ALLELE FREQUENCIES 645 Human Evolution 676 THE EFFECTS OF POPULATION SIZE 646 HUMANS AND THE GREAT APES 676 PROBLEM-SOLVING SKILLS Applying Genetic Drift HUMAN EVOLUTION IN THE FOSSIL RECORD 676 to Pitcairn Island 647 DNA SEQUENCE VARIATION AND HUMAN ORIGINS 677 Populations in Genetic Equilibrium 647 BALANCING SELECTION 648 Appendices MUTATION-SELECTION BALANCE 649 Appendix A:The Rules of Probability 685 MUTATION-DRIFT BALANCE 650 Appendix B:Binomial Probabilities 687 Appendix C:In Situ Hybridization 689 CHAPTER 24 Appendix D:Evidence for an Unstable Messenger RNA 691 Evolutionary Genetics 656 Appendix E:Evolutionary Rates 693 D'ou venons nous?Que sommes nous?Ou allons Answers to Odd-Numbered Questions n0us?656 and Problems 697 The Emergence of Evolutionary Theory 657 Glossary 720 DARWIN'S THEORY OF EVOLUTION 657 EVOLUTIONARY GENETICS 658 Photo Credits 743 Genetic Variation in Natural Populations 659 Illustration Credits 745 VARIATION IN PHENOTYPES 659 VARIATION IN CHROMOSOME STRUCTURE 660 Index 746 xviii
xviii CHAPTER 2 3 Population Genetics 634 A Remote Colony 634 The Theory of Allele Frequencies 635 ESTIMATING ALLELE FREQUENCIES 635 RELATING GENOTYPE FREQUENCIES TO ALLELE FREQUENCIES: THE HARDY–WEINBERG PRINCIPLE 636 APPLICATIONS OF THE HARDY–WEINBERG PRINCIPLE 636 EXCEPTIONS TO THE HARDY–WEINBERG PRINCIPLE 638 SOLVE IT The Effects of Inbreeding on HardyWeinberg Frequencies 639 USING ALLELE FREQUENCIES IN GENETIC COUNSELING 640 Natural Selection 641 THE CONCEPT OF FITNESS 641 NATURAL SELECTION AT THE LEVEL OF THE GENE 642 SOLVE IT Selection Against a Harmful Recessive Allele 643 Random Genetic Drift 645 RANDOM CHANGES IN ALLELE FREQUENCIES 645 THE EFFECTS OF POPULATION SIZE 646 PROBLEM-SOLVING SKILLS Applying Genetic Drift to Pitcairn Island 647 Populations in Genetic Equilibrium 647 BALANCING SELECTION 648 MUTATION-SELECTION BALANCE 649 MUTATION-DRIFT BALANCE 650 CHAPTER 2 4 Evolutionary Genetics 656 D’ou venons nous? Que sommes nous? Ou allons nous? 656 The Emergence of Evolutionary Theory 657 DARWIN’S THEORY OF EVOLUTION 657 EVOLUTIONARY GENETICS 658 Genetic Variation in Natural Populations 659 VARIATION IN PHENOTYPES 659 VARIATION IN CHROMOSOME STRUCTURE 660 VARIATION IN PROTEIN STRUCTURE 661 VARIATION IN NUCLEOTIDE SEQUENCES 661 Molecular Evolution 662 MOLECULES AS “DOCUMENTS OF EVOLUTIONARY HISTORY” 663 MOLECULAR PHYLOGENIES 664 RATES OF MOLECULAR EVOLUTION 664 PROBLEM-SOLVING SKILLS Using Mitochondrial DNA to Establish a Phylogeny 665 THE MOLECULAR CLOCK 667 SOLVE IT Calculating Divergence Times 667 VARIATION IN THE EVOLUTION OF PROTEIN SEQUENCES 667 VARIATION IN THE EVOLUTION OF DNA SEQUENCES 668 THE NEUTRAL THEORY OF MOLECULAR EVOLUTION 669 SOLVE IT Evolution by Mutation and Genetic Drift 670 MOLECULAR EVOLUTION AND PHENOTYPIC EVOLUTION 670 Speciation 672 WHAT IS A SPECIES? 672 MODES OF SPECIATION 674 Human Evolution 676 HUMANS AND THE GREAT APES 676 HUMAN EVOLUTION IN THE FOSSIL RECORD 676 DNA SEQUENCE VARIATION AND HUMAN ORIGINS 677 Appendices Appendix A: The Rules of Probability 685 Appendix B: Binomial Probabilities 687 Appendix C: In Situ Hybridization 689 Appendix D: Evidence for an Unstable Messenger RNA 691 Appendix E: Evolutionary Rates 693 Answers to Odd-Numbered Questions and Problems 697 Glossary 720 Photo Credits 743 Illustration Credits 745 Index 746
The Science of Genetics CHAPTER OUTLINE An Invitation Three Great Milestones in Genetics The Personal Genome DNA as the Genetic Material Genetics and Evolution Each of us is composed of trillions of cells,and each of those cells contains very thin fibers a few centimeters long that play Levels of Genetic Analysis a major role in who we are,as human beings and as persons. These all-important intracellular fibers are made of DNA.Every Genetics in the World:Applications of Genetics to Human Endeavors time a cell divides,its DNA is replicated and apportioned equally to two daughter cells.The DNA content of these cells-what we call the genome-is thereby conserved.This genome is a master set of instructions,in fact a whole library of information,that cells use to maintain the living state.Ultimately.all the activities of a cell depend on it.To know the DNA is therefore to know the cell,and,in a larger sense,to know the organism to which that cell belongs. Given the importance of the DNA,it should come as no surprise that great efforts have been expended to study it,down to the finest details.In fact,in the last decade of the twentieth century a worldwide campaign,the Human Genome Project,took shape,and in 2001 it produced a comprehensive analysis of human DNA samples that had been collected from a small number of anonymous donors. This work-stunning in scope and significance-laid the foundation for all future research on the human genome.Then,in 2007,the analysis of human DNA took a new turn.Two of the architects of the Human Genome Project had their own DNA decoded.The technol- ogy for analyzing complete genomes has advanced significantly,and the cost for this analysis is no longer exorbitant.In fact,it may soon be possible for each of us to have our own genome analyzed-a prospect that is sure to influence our lives and change how we think about ourselves. Computer artwork of deoxyribonucleic acid (DNA]. 1
1 1 The Science of Genetics The Personal Genome Each of us is composed of trillions of cells, and each of those cells contains very thin fibers a few centimeters long that play a major role in who we are, as human beings and as persons. These all-important intracellular fibers are made of DNA. Every time a cell divides, its DNA is replicated and apportioned equally to two daughter cells. The DNA content of these cells—what we call the genome—is thereby conserved. This genome is a master set of instructions, in fact a whole library of information, that cells use to maintain the living state. Ultimately, all the activities of a cell depend on it. To know the DNA is therefore to know the cell, and, in a larger sense, to know the organism to which that cell belongs. Given the importance of the DNA, it should come as no surprise that great efforts have been expended to study it, down to the finest details. In fact, in the last decade of the twentieth century a worldwide campaign, the Human Genome Project, took shape, and in 2001 it produced a comprehensive analysis of human DNA samples that had been collected from a small number of anonymous donors. This work—stunning in scope and significance—laid the foundation for all future research on the human genome. Then, in 2007, the analysis of human DNA took a new turn. Two of the architects of the Human Genome Project had their own DNA decoded. The technology for analyzing complete genomes has advanced significantly, and the cost for this analysis is no longer exorbitant. In fact, it may soon be possible for each of us to have our own genome analyzed—a prospect that is sure to influence our lives and change how we think about ourselves. An Invitation Three Great Milestones in Genetics DNA as the Genetic Material Genetics and Evolution Levels of Genetic Analysis Genetics in the World: Applications of Genetics to Human Endeavors CHAPTER OUTLINE Computer artwork of deoxyribonucleic acid (DNA).
2 Chapter 1 The Science of Genetics An Invitation This book is about genetics,the science that deals with DNA.Genetics is also one of the sciences that has a profound impact on us.Through applications in agriculture and medicine,it helps to feed us and keep us healthy.It also provides insight into what makes us human and into what distinguishes each of us as individuals.Genetics is a relatively young science-it emerged only at the beginning of the twentieth century, but it has grown in scope and significance,so much so that it now has a prominent,and some would say commanding,position in all of biology. Genetics began with the study of how the characteristics of organisms are passed from parents to offspring-that is,how they are inherited.Until the middle of the twentieth century,no one knew for sure what the hereditary material was.However, geneticists recognized that this material had to fulfill three requirements.First,it had to replicate so that copies could be transmitted from parents to offspring.Second,it had to encode information to guide the development,functioning,and behavior of cells and the organisms to which they belong.Third,it had to change,even if only once in a great while,to account for the differences that exist among individuals.For several decades,geneticists wondered what the hereditary material could be.Then in 1953 the structure of DNA was elucidated and genetics had its great clarifying moment. In a relatively short time,researchers discovered how DNA functions as the hereditary material-that is,how it replicates,how it encodes and expresses information,and how it changes.These discoveries ushered in a new phase of genetics in which phe- nomena could be explained at the molecular level.In time,geneticists learned how to analyze the DNA of whole genomes,including our own.This progress-from studies of heredity to studies of whole genomes-has been amazing. As practicing geneticists and as teachers,we have written this book to explain the science of genetics to you.As its title indicates,this book is designed to convey the principles of genetics,and to do so in sufficient detail for you to understand them clearly.We invite you to read each chapter,to study its illustrations,and to wrestle with the questions and problems at the chapter's end.We all know that learning- and research,teaching,and writing too-takes effort.As authors,we hope your effort studying this book will be rewarded with a good understanding of genetics. This introductory chapter provides an overview of what we will explain in more detail in the chapters to come.For some of you,it will be a review of knowledge gained from studying basic biology and chemistry.For others,it will be new fare.Our advice is to read the chapter without dwelling on the details.The emphasis here is on the grand themes that run through genetics.The many details of genetics theory and practice will come later. Three Great Milestones in Genetics Genetics is rooted in the research of Gregor Scientific knowledge and understanding usually advance incremen- Mendel,a monk who discovered how traits tally.In this book we will examine the advances that have occurred in genetics during its short history-barely a hundred years.Three are inherited.The molecular basis of heredity great milestones stand out in this history:(1)the discovery of rules was revealed when James Watson and Fran- governing the inheritance of traits in organisms;(2)the identifica- tion of the material responsible for this inheritance and the eluci- cis Crick elucidated the structure of DNA.The dation of its structure;and (3)the comprehensive analysis of the Human Genome Project is currently engaged hereditary material in human beings and other organisms. in the detailed analysis of human DNA MENDEL:GENES AND THE RULES OF INHERITANCE Although genetics developed during the twentieth century,its origin is rooted in the work of Gregor Mendel Figure 1.1),a Moravian monk who lived in the nineteenth
2 Chapter 1 The Science of Genetics An Invitation This book is about genetics, the science that deals with DNA. Genetics is also one of the sciences that has a profound impact on us. Through applications in agriculture and medicine, it helps to feed us and keep us healthy. It also provides insight into what makes us human and into what distinguishes each of us as individuals. Genetics is a relatively young science—it emerged only at the beginning of the twentieth century, but it has grown in scope and signifi cance, so much so that it now has a prominent, and some would say commanding, position in all of biology. Genetics began with the study of how the characteristics of organisms are passed from parents to offspring—that is, how they are inherited. Until the middle of the twentieth century, no one knew for sure what the hereditary material was. However, geneticists recognized that this material had to fulfi ll three requirements. First, it had to replicate so that copies could be transmitted from parents to offspring. Second, it had to encode information to guide the development, functioning, and behavior of cells and the organisms to which they belong. Third, it had to change, even if only once in a great while, to account for the differences that exist among individuals. For several decades, geneticists wondered what the hereditary material could be. Then in 1953 the structure of DNA was elucidated and genetics had its great clarifying moment. In a relatively short time, researchers discovered how DNA functions as the hereditary material—that is, how it replicates, how it encodes and expresses information, and how it changes. These discoveries ushered in a new phase of genetics in which phenomena could be explained at the molecular level. In time, geneticists learned how to analyze the DNA of whole genomes, including our own. This progress—from studies of heredity to studies of whole genomes—has been amazing. As practicing geneticists and as teachers, we have written this book to explain the science of genetics to you. As its title indicates, this book is designed to convey the principles of genetics, and to do so in suffi cient detail for you to understand them clearly. We invite you to read each chapter, to study its illustrations, and to wrestle with the questions and problems at the chapter’s end. We all know that learning— and research, teaching, and writing too—takes effort. As authors, we hope your effort studying this book will be rewarded with a good understanding of genetics. This introductory chapter provides an overview of what we will explain in more detail in the chapters to come. For some of you, it will be a review of knowledge gained from studying basic biology and chemistry. For others, it will be new fare. Our advice is to read the chapter without dwelling on the details. The emphasis here is on the grand themes that run through genetics. The many details of genetics theory and practice will come later. Three Great Milestones in Genetics Scientifi c knowledge and understanding usually advance incrementally. In this book we will examine the advances that have occurred in genetics during its short history—barely a hundred years. Three great milestones stand out in this history: (1) the discovery of rules governing the inheritance of traits in organisms; (2) the identifi cation of the material responsible for this inheritance and the elucidation of its structure; and (3) the comprehensive analysis of the hereditary material in human beings and other organisms. MENDEL: GENES AND THE RULES OF INHERITANCE Although genetics developed during the twentieth century, its origin is rooted in the work of Gregor Mendel ( Figure 1.1), a Moravian monk who lived in the nineteenth Genetics is rooted in the research of Gregor Mendel, a monk who discovered how traits are inherited. The molecular basis of heredity was revealed when James Watson and Francis Crick elucidated the structure of DNA. The Human Genome Project is currently engaged in the detailed analysis of human DNA.