(BQ) Part 1 book Genetics - A conceptual approad has contents: Introduction to genetics, chromosomes and cellular reproduction, basic principles of heredity, chromosome variation, bacterial and viral genetic systems chromosome structure and organelle DNA,... and other contents.
Genetics A Conceptual Approach sixth edition Benjamin A Pierce Southwestern University Vice President, STEM: Ben Roberts Executive Editor: Lauren Schultz Development Editor: Maria Lokshin Executive Marketing Manager: Will Moore Marketing Assistant: Cate McCaffery Director of Content: Clairissa Simmons Content Development Manager, Biology: Amber Jonker Lead Content Developer, Genetics: Cassandra Korsvik Senior Media and Supplements Editor: Amy Thorne Assistant Editor: Shannon Moloney Director, Content Management Enhancement: Tracey Kuehn Managing Editor: Lisa Kinne Project Management: J Carey Publishing Service Manuscript Editor: Norma Sims Roche Director of Design, Content Management: Diana Blume Interior and Cover Design: Blake Logan Illustrations: Dragonfly Media Group Illustration Coordinator: Janice Donnola Photo Editor: Christine Buese Photo Researcher: Richard Fox Senior Production Supervisor: Paul Rohloff Composition: codeMantra Printing and Binding: LSC Communications Cover and Title Page Illustration: Echo Medical Media/PDB data entry 5F9R Library of Congress Control Number: 2016955732 © 2017, 2014, 2012, 2008 by W H Freeman and Company All rights reserved ISBN 978-1-319-05096-2 (EPUB) Printed in the United States of America First printing W H Freeman and Company One New York Plaza Suite 4500 New York, NY 10004-1562 www.macmillanlearning.com To my parents, Rush and Amanda Pierce; my children, Sarah Pierce Dumas and Michael Pierce; and my genetic partner, friend, and soul mate for 36 years, Marlene Tyrrell Contents in Brief Introduction to Genetics Chromosomes and Cellular Reproduction Basic Principles of Heredity Sex Determination and Sex-Linked Characteristics Extensions and Modifications of Basic Principles Pedigree Analysis, Applications, and Genetic Testing Linkage, Recombination, and Eukaryotic Gene Mapping Chromosome Variation Bacterial and Viral Genetic Systems 10 DNA: The Chemical Nature of the Gene 11 Chromosome Structure and Organelle DNA 12 DNA Replication and Recombination 13 Transcription 14 RNA Molecules and RNA Processing 15 The Genetic Code and Translation 16 Control of Gene Expression in Bacteria 17 Control of Gene Expression in Eukaryotes 18 Gene Mutations and DNA Repair 19 Molecular Genetic Analysis and Biotechnology 20 21 22 23 24 25 26 Genomics and Proteomics Epigenetics Developmental Genetics and Immunogenetics Cancer Genetics Quantitative Genetics Population Genetics Evolutionary Genetics Reference Guide to Model Genetic Organisms Working with Fractions: A Review Glossary Answers to Selected Problems Index Contents Letter from the Author Preface Chapter Introduction to Genetics Albinism in the Hopis 1.1 Genetics Is Important to Us Individually, to Society, and to the Study of Biology The Role of Genetics in Biology Genetic Diversity and Evolution DNA in the Biosphere Divisions of Genetics Model Genetic Organisms 1.2 Humans Have Been Using Genetic Techniques for Thousands of Years The Early Use and Understanding of Heredity The Rise of the Science of Genetics The Cutting Edge of Genetics 1.3 A Few Fundamental Concepts Are Important for the Start of Our Journey into Genetics Chapter Chromosomes and Cellular Reproduction The Blind Men’s Riddle 2.1 Prokaryotic and Eukaryotic Cells Differ in a Number of Genetic Characteristics 2.2 Cell Reproduction Requires the Copying of the Genetic Material, Separation of the Copies, and Cell Division Prokaryotic Cell Reproduction by Binary Fission Eukaryotic Cell Reproduction The Cell Cycle and Mitosis Genetic Consequences of the Cell Cycle CONNECTING CONCEPTS Counting Chromosomes and DNA Molecules 2.3 Sexual Reproduction Produces Genetic Variation Through the Process of Meiosis Meiosis Sources of Genetic Variation in Meiosis CONNECTING CONCEPTS Mitosis and Meiosis Compared The Separation of Sister Chromatids and Homologous Chromosomes Meiosis in the Life Cycles of Animals and Plants Chapter Basic Principles of Heredity The Genetics of Blond Hair in the South Pacific 3.1 Gregor Mendel Discovered the Basic Principles of Heredity Mendel’s Success Genetic Terminology 3.2 Monohybrid Crosses Reveal the Principle of Segregation and the Concept of Dominance What Monohybrid Crosses Reveal CONNECTING CONCEPTS Relating Genetic Crosses to Meiosis The Molecular Nature of Alleles Predicting the Outcomes of Genetic Crosses The Testcross Genetic Symbols CONNECTING CONCEPTS Ratios in Simple Crosses 3.3 Dihybrid Crosses Reveal the Principle of Independent Assortment Dihybrid Crosses The Principle of Independent Assortment Relating the Principle of Independent Assortment to Meiosis Applying Probability and the Branch Diagram to Dihybrid Crosses The Dihybrid Testcross 3.4 Observed Ratios of Progeny May Deviate from Expected Ratios by Chance The Chi-Square Goodness-of-Fit Test Chapter Sex Determination and Sex-Linked Characteristics The Sex of a Dragon 4.1 Sex Is Determined by a Number of Different Mechanisms Chromosomal Sex-Determining Systems Genic Sex Determination Environmental Sex Determination Sex Determination in Drosophila melanogaster Sex Determination in Humans 4.2 Sex-Linked Characteristics Are Determined by Genes on the Sex Chromosomes X-Linked White Eyes in Drosophila Nondisjunction and the Chromosome Theory of Inheritance X-Linked Color Blindness in Humans Symbols for X-Linked Genes Z-Linked Characteristics Y-Linked Characteristics CONNECTING CONCEPTS Recognizing Sex-Linked inheritance 4.3 Dosage Compensation Equalizes the Amount of Protein Produced by X-Linked and Autosomal Genes in Some Animals The Lyon Hypothesis Mechanism of Random X Inactivation Chapter Extensions and Modifications of Basic Principles The Odd Genetics of Left-Handed Snails 5.1 Additional Factors at a Single Locus Can Affect the Results of Genetic Crosses Types of Dominance Penetrance and Expressivity Lethal Alleles Multiple Alleles 5.2 Gene Interaction Takes Place When Genes at Multiple Loci Determine a Single Phenotype Introns are removed from pre-mRNA within a structure called the spliceosome, which is composed of several small nuclear RNAs and proteins Some introns found in rRNA genes and mitochondrial genes are selfsplicing Some pre-mRNAs undergo alternative processing, in which different combinations of exons are spliced together or different 3′ cleavage sites are used Messenger RNAs may be altered by the addition, deletion, or modification of nucleotides in the coding sequence, a process called RNA editing Transfer RNAs, which attach to amino acids, are short molecules that assume a common secondary structure and contain modified bases Ribosomes, the sites of protein synthesis, are composed of several ribosomal RNA molecules and numerous proteins Small interfering RNAs, microRNAs, Piwi-interacting RNAs, and CRISPR RNAs play important roles in gene silencing and in a number of other biological processes Long noncoding RNAs are RNA molecules that not encode proteins Evidence increasingly suggests that many of these molecules function in the control of gene expression Circular noncoding RNAs may serve as decoys for miRNAs IMPORTANT TERMS colinearity exon intron group I intron group II intron nuclear pre-mRNA intron transfer RNA intron codon 5′ untranslated region (5′ UTR) Shine–Dalgarno sequence protein-coding region 3′ untranslated region (3′ UTR) 5′ cap poly(A) tail RNA splicing 5′ splice site 3′ splice site branch point spliceosome lariat trans-splicing recursive splicing alternative processing pathway alternative splicing multiple 3′ cleavage sites RNA editing guide RNA (gRNA) modified base tRNA-modifying enzyme cloverleaf anticodon large ribosomal subunit small ribosomal subunit RNA interference (RNAi) RNA-induced silencing complex (RISC) long noncoding RNA (lncRNA) enhancer RNA (eRNA) ANSWERS TO CONCEPT CHECKS When DNA was hybridized to the mRNA transcribed from it, regions of DNA that did not correspond to RNA looped out Group I introns, group II introns, nuclear pre-mRNA introns, and transfer RNA introns A protein that adds the 5′ cap is associated with RNA polymerase II, which transcribes pre-mRNAs, but is absent from RNA polymerases I and III, which transcribe rRNAs and tRNAs, respectively b c Guide RNA b d An siRNA or miRNA combines with proteins to form a RISC, which then pairs with mRNA through complementary pairing between bases on the siRNA or miRNA and bases on the mRNA WORKED PROBLEMS Problem DNA from a eukaryotic gene was isolated, denatured, and hybridized to the mRNA transcribed from the gene; the hybridized structure was then observed with an electron microscope The adjoining diagram shows the structure that was observed a How many introns and exons are there in this gene? Explain your answer b Identify and label the exons and introns in this hybridized structure Solution Strategy What information is required in your answer to the problem? a The number of introns and exons and how you arrived at your answer b The location of the introns and exons labeled on the figure What information is provided to solve the problem? The DNA and mRNA are from a eukaryote The DNA was denatured and hybridized to the mRNA A diagram of the hybridized structure For help with this problem, review: Introns in Section 14.1 and Figure 14.2 Solution Steps a Each of the loops represents a region in which sequences in the DNA not have corresponding sequences in the RNA; these regions are introns There are five loops in the hybridized structure; so there must be five introns in the DNA and six exons Recall: Introns are noncoding sequences found within eukaryotic genes b Hint: The number of introns will be one less than the number of exons Problem Draw a typical bacterial mRNA and the gene from which it was transcribed Identify the 5′ and 3′ ends of the RNA and DNA molecules, as well as the following regions or sequences: a Promoter b 5′ untranslated region c 3′ untranslated region d Protein-coding sequence e Transcription start site f Terminator g Shine–Dalgarno sequence h Start and stop codons Solution Strategy What information is required in your answer to the problem? A drawing of an mRNA molecule and the gene from which it is transcribed The 5′ and 3′ ends of the mRNA and DNA molecules Locations of the listed structures on the drawing What information is provided to solve the problem? The gene is from a bacterium Different parts of the DNA and RNA that are to be labeled For help with this problem, review: The Template in Section 13.2 and The Structure of Messenger RNA in Section 14.2 Solution Strategy Hint: Review the structure of a transcription unit in Figure 13.6 and the structure of mRNA in Figure 14.5 COMPREHENSION QUESTIONS Section 14.1 What is the concept of colinearity? In what way is this concept fulfilled in bacterial and eukaryotic cells? What are some characteristics of introns? What are the four basic types of introns? In which organisms are they found? Section 14.2 What are the three primary regions of mRNA sequences in bacterial cells? What is the function of the Shine–Dalgarno consensus sequence? What is the 5′ cap? How is the 5′ cap added to eukaryotic pre-mRNA? What is the function of the 5′ cap? How is the poly(A) tail added to pre-mRNA? What is the purpose of the poly(A) tail? What makes up the spliceosome? What is the function of the spliceosome? Explain the process of pre-mRNA splicing in nuclear genes 10 Describe two types of alternative processing pathways How these pathways lead to the production of multiple proteins from a single gene? 11 What is RNA editing? Explain the role of guide RNAs in RNA editing 12 Summarize the different types of processing that can take place in premRNA Section 14.3 13 What are some of the modifications in tRNA that take place through processing? Section 14.4 14 Describe the basic structure of ribosomes in bacterial and in eukaryotic cells 15 Explain how rRNA is processed Section 14.5 16 What is the origin of small interfering RNAs, microRNAs, and Piwiinteracting RNAs? What these RNA molecules in the cell? 17 What are some similarities and differences between siRNAs and miRNAs? 18 What role CRISPR-Cas systems naturally play in bacteria? 19 Outline the three stages of CRISPR-Cas action 20 Explain how some lncRNAs serve as molecular decoys for RNA-binding proteins and miRNAs APPLICATION QUESTIONS AND PROBLEMS Section 14.1 *21 Duchenne muscular dystrophy is caused by a mutation in a gene that comprises 2.5 million base pairs and specifies a protein called dystrophin However, less than 1% of the gene actually encodes the amino acids in the dystrophin protein On the basis of what you now know about gene structure and RNA processing in eukaryotic cells, provide a possible explanation for the large size of the dystrophin gene 22 What would happen in the experiment illustrated in Figure 14.2 if the DNA and RNA that are mixed together came from very different organisms, for example a worm and a pig? 23 For the ovalbumin gene shown in Figure 14.3, where would the 5′ untranslated region and 3′ untranslated regions be located in the DNA and in the RNA? Section 14.2 24 How the mRNAs of bacterial cells and the pre-mRNAs of eukaryotic cells differ? How the mature mRNAs of bacterial and eukaryotic cells differ? 25 Are the 5′ untranslated regions (5′ UTR) of eukaryotic mRNAs encoded by sequences in the promoter, exon, or intron of the gene? Explain your answer *26 Draw a typical eukaryotic gene and the pre-mRNA and mRNA derived from it Assume that the gene contains three exons Identify the following items and, for each item, give a brief description of its function: a 5′ untranslated region b Promoter c AAUAAA consensus sequence d Transcription start site e 3′ untranslated region f Introns g Exons h Poly(A) tail i 5′ cap 27 How would the deletion of the Shine–Dalgarno sequence affect a bacterial mRNA? 28 What would be the most likely effect of moving the AAUAAA consensus sequence shown in Figure 14.7 10 nucleotides upstream? 29 How would the deletion of the following sequences or features most likely affect a eukaryotic pre-mRNA? a AAUAAA consensus sequence b 5′ cap c Poly(A) tail 30 Suppose that a mutation occurs in the middle of a large intron of a gene encoding a protein What would be the most likely effect of the mutation on the amino acid sequence of that protein? Explain your answer *31 A geneticist induces a mutation in a cell line growing in the laboratory The mutation occurs in a gene that encodes a protein that participates in the cleavage and polyadenylation of eukaryotic mRNA What will be the immediate effect of this mutation on RNA molecules in the cultured cells? 32 A geneticist induces a mutation in a cell line growing in the laboratory The mutation occurs in a gene that encodes a protein that binds to the poly(A) tail of eukaryotic mRNA What will be the immediate effect of this mutation in the cultured cells? 33 A geneticist isolates a gene that contains eight exons He then isolates the mature mRNA produced by this gene After making the DNA single stranded, he mixes the single-stranded DNA with the mRNA Some of the single-stranded DNA hybridizes (pairs) with the complementary mRNA Draw a picture of what the DNA–RNA hybrids will look like under the electron microscope 34 A geneticist discovers that two different proteins are encoded by the same gene One protein has 56 amino acids, and the other has 82 amino acids Provide a possible explanation for how the same gene can encode both of these proteins 35 Suppose that a 20-bp deletion occurs in the middle of exon of the gene depicted in Figure 14.12a What will be the likely effect of this deletion in the proteins produced by alternative splicing? *36 Explain how each of the following processes complicates the concept of colinearity a Trans-splicing b Alternative splicing c RNA editing Section 14.5 37 RNA interference may be triggered when inverted repeats are transcribed into an RNA molecule that then folds to form doublestranded RNA Write out a sequence of inverted repeats within an RNA molecule Using a diagram, show how the RNA with the inverted repeats can fold to form double-stranded RNA 38 In the early 1990s, Carolyn Napoli and her colleagues were working on petunias, attempting to genetically engineer a variety with dark purple petals by introducing numerous copies of a gene that encodes purple pigment in the flower petals (C Napoli, C Lemieux, and R Jorgensen 1990 Plant Cell 2:279–289) Their thinking was that extra copies of the gene would cause more purple pigment to be produced and would result in a petunia with an even darker hue of purple However, much to their surprise, many of the plants carrying extra copies of the purple gene were completely white or had only patches of color Molecular analysis revealed that the amount of mRNA produced by the purple gene was reduced 50-fold in the engineered plants compared with wild-type plants Somehow, the introduction of extra copies of the purple gene silenced both the introduced copies and the plant’s own purple genes Provide a possible explanation for how the introduction of numerous copies of the purple gene silenced all copies of the purple gene White petunia [roger ashford/Alamy.] CHALLENGE QUESTIONS Section 14.2 Alternative splicing takes place in more than 95% of the human protein-encoding genes with multiple exons Researchers have found that how a pre-mRNA is spliced is affected by the pre-mRNA’s promoter sequence (D Auboeuf et al 2002 Science 298:416–419) In addition, factors that affect the rate of elongation by the RNA polymerase during transcription affect the type of splicing that takes place These findings suggest that the process of transcription affects splicing Propose one or more mechanisms that would explain how transcription might affect alternative splicing 40 Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disease caused by mutations in the gene that encodes dystrophin, a large protein that plays an important role in the development of normal muscle fibers The dystrophin gene is immense, spanning 2.5 million base pairs, and includes 79 exons and 78 introns Many of the mutations that cause DMD produce premature stop codons, which bring protein synthesis to a halt, resulting in a greatly shortened and nonfunctional 39 form of dystrophin Some geneticists have proposed treating DMD patients by causing the spliceosome to skip the exon containing the stop codon Exon skipping would produce a protein that is somewhat shortened (because an exon is skipped and some amino acids are missing), but might still result in a protein that had some function (A Goyenvalle et al 2004 Science 306:1796–1799) Propose a possible mechanism to bring about exon skipping for the treatment of DMD 41 In eukaryotic cells, a poly(A) tail is normally added to pre-mRNA, but not to rRNA or tRNA With the use of recombinant DNA techniques, a protein-encoding gene (which is normally transcribed by RNA polymerase II) can be connected to a promoter for RNA polymerase I This hybrid gene is subsequently transcribed by RNA polymerase I, and the appropriate pre-mRNA is produced, but this pre-mRNA is not cleaved at the 3′ end, and a poly(A) tail is not added Propose a mechanism to explain how the type of promoter found at the 5′ end of a gene can affect whether a poly(A) tail is added to the 3′ end 42 SR proteins are essential to proper spliceosome assembly and are known to take part in the regulation of alternative splicing Surprisingly, the role of SR proteins in splice-site selection and alternative splicing is affected by the promoter used for the transcription of the pre-mRNA For example, through genetic engineering, RNA polymerase II promoters that have somewhat different sequences can be created When pre-mRNAs with exactly the same sequences are transcribed from two different RNA polymerase II promoters that differ slightly in sequence, which promoter is used can affect how the pre-mRNA is spliced Propose a mechanism by which the DNA sequence of an RNA polymerase II promoter could affect alternative splicing of pre-mRNA THINK-PAIR-SHARE QUESTIONS Section 14.1 Eukaryotic genes are often interrupted by noncoding introns What might be some possible reasons that organisms have evolved introns? And why might other organisms lose introns? Suppose that you are at a party on Friday night, relaxing after your big genetics exam Someone comes up to you and, hearing that you just finished your genetics exam, says, “What exactly is a gene?” How would you respond? What are the strengths and weaknesses of your definition of a gene? Section 14.2 Many human genetic diseases are caused by mutations that occur at splice sites Propose some ways that mutations at the 5′ splice site, 3′ splice site, and branch point might disrupt splicing and alter the phenotype Section 14.5 Small RNA molecules are involved in numerous genetic processes, including replication, translation, mRNA processing and degradation, inhibition of translation, chromatin modification, and protection against viruses and transposable elements However, small DNA molecules have little or no role in these functions Why has RNA and not DNA evolved to carry out these functions? The number of microRNAs encoded by the genome varies widely among organisms: some species have many miRNA genes and other species have relatively few Researchers have determined the number of miRNA genes possessed by different species and have made the following observations: a The number of miRNA genes found on a chromosome is not correlated with chromosome length In other words, longer chromosomes not necessarily have more miRNA genes b Most species show a strong positive correlation between the number of miRNA genes on a chromosome and the number of non-proteinencoding genes on that chromosome In other words, chromosomes with more non-protein-encoding genes have more miRNA genes c Many species display a strong positive correlation between the number of miRNA genes on a chromosome and the number of proteinencoding genes on that chromosome In other words, chromosomes with more protein-encoding genes have more miRNA genes Propose possible explanations for these observations Self-study tools that will help you practice what you’ve learned and reinforce this chapter’s concepts are available online Go to www.macmillanlearning.com/PierceGenetics6e ... Factors and Transcriptional Regulator Proteins Transcriptional Activators and Coactivators Transcriptional Repressors Enhancers and Insulators Regulation of Transcriptional Stalling and Elongation... CONCEPTS The Basic Pathway of DNA Repair Repair of Double-Strand Breaks Translesion DNA Polymerases Genetic Diseases and Faulty DNA Repair Chapter 19 Molecular Genetic Analysis and Biotechnology... Conjugation, Transformation, and Transduction Conjugation Natural Gene Transfer and Antibiotic Resistance Transformation in Bacteria Bacterial Genome Sequences Horizontal Gene Transfer Bacterial