Genetics in the World:Applications of Genetics to Human Endeavors 13 Angus Beef master Simmental Charolais FIGURE 1.11 Breeds of beef cattle. came to be quite different from their wild ancestors.For example,cattle were changed in appearance and behavior(Figure 1.11),and corn,which is descended from a wild grass called teosinte(Figure 1.12),was changed so much that it could no longer grow without human cultivation. Selective breeding programs-now informed by genetic theory-continue to play important roles in agriculture.High-yielding varieties of wheat,corn,rice,and many other plants have been developed by breeders to feed a growing human population. Selective breeding techniques have also been applied to animals such as beef and dairy cattle,swine,and sheep,and to horticultural plants such as shade trees,turf grass,and garden flowers. Beginning in the 1980s,classical approaches to crop and livestock improvement were supplemented-and in some cases,supplanted-by approaches from molecular genetics.Detailed genetic maps of the chromosomes of several species were con- structed to pinpoint genes of agricultural significance.By locating genes for traits such as grain yield or disease resistance,breeders could now design schemes to in- corporate particular alleles into agricultural varieties.These mapping projects have been carried on relentlessly and for a few species have culminated in the complete sequencing of the genome.Other crop and livestock genome sequencing projects are still in progress.All sorts of potentially useful genes are being identified and studied in these projects. Plant and animal breeders are also employing the techniques of molecular genet- ics to introduce genes from other species into crop plants and livestock.This process of changing the genetic makeup of an organism was initially developed using test spe- cies such as fruit flies.Today it is widely used to augment the genetic material of many kinds of creatures.Plants and animals that have been altered by the introduction of foreign genes are called GMOs-genetically modified organisms.BT corn is an example. Many corn varieties now grown in the United States carry a gene from the bacterium 6.5cm FIGURE 1.12 Ears of corn (right) and its ancestor,teosinte [left]
Genetics in the World: Applications of Genetics to Human Endeavors 13 came to be quite different from their wild ancestors. For example, cattle were changed in appearance and behavior ( Figure 1.11), and corn, which is descended from a wild grass called teosinte ( Figure 1.12), was changed so much that it could no longer grow without human cultivation. Selective breeding programs—now informed by genetic theory—continue to play important roles in agriculture. High-yielding varieties of wheat, corn, rice, and many other plants have been developed by breeders to feed a growing human population. Selective breeding techniques have also been applied to animals such as beef and dairy cattle, swine, and sheep, and to horticultural plants such as shade trees, turf grass, and garden fl owers. Beginning in the 1980s, classical approaches to crop and livestock improvement were supplemented—and in some cases, supplanted—by approaches from molecular genetics. Detailed genetic maps of the chromosomes of several species were constructed to pinpoint genes of agricultural signifi cance. By locating genes for traits such as grain yield or disease resistance, breeders could now design schemes to incorporate particular alleles into agricultural varieties. These mapping projects have been carried on relentlessly and for a few species have culminated in the complete sequencing of the genome. Other crop and livestock genome sequencing projects are still in progress. All sorts of potentially useful genes are being identifi ed and studied in these projects. Plant and animal breeders are also employing the techniques of molecular genetics to introduce genes from other species into crop plants and livestock. This process of changing the genetic makeup of an organism was initially developed using test species such as fruit fl ies. Today it is widely used to augment the genetic material of many kinds of creatures. Plants and animals that have been altered by the introduction of foreign genes are called GMOs—genetically modifi ed organisms. BT corn is an example. Many corn varieties now grown in the United States carry a gene from the bacterium 6.5 cm FIGURE 1.12 Ears of corn (right) and its ancestor, teosinte (left). FIGURE 1.11 Breeds of beef cattle. Angus Beef master Simmental Charolais Armin Floreth/imagebroker/ Alamy
14 Chapter 1 The Science of Genetics Bacillus thuringiensis.This gene encodes a pro- tein that is toxic to many insects.Corn strains that carry the gene for BT toxin are resistant to attacks by the European corn borer,an insect that has caused enormous damage in the past Figure 1.13).Thus,BT corn plants produce their own insecticide. The development and use of GMOs has stirred up controversy worldwide.For example, @ ( African and European countries have been re- luctant to grow BT corn or to purchase BT corn FIGURE 1.13 Use of a genetically modified plant in agriculture.(a)European corn grown in the United States.Their reluctance is borer eating away the stalk of a corn plant.(b)Side-by-side comparison of corn stalks due to several factors,including the conflicting from plants that are resistant (top)and susceptible (bottom)to the corn borer.The interests of small farmers and large agricultural resistant plant is expressing a gene for an insecticidal protein derived from Bacillus corporations,and concerns about the safety of thuringiensis consuming genetically modified food.There is also a concern that BT corn might kill nonpest species of insects such as butterflies and honeybees.Advances in molecular genetics have provided the tools and the materials to change agriculture profoundly.Today, policy makers are wrestling with the implications of these new technologies. GENETICS IN MEDICINE Classical genetics has provided physicians with a long list of diseases that are caused by mutant genes.The study of these diseases began shortly after Mendel's work was rediscovered.In 1909 Sir Archibald Garrod,a British physician and biochemist,pub- lished a book entitled Inborn Errors of Metabolism.In this book Garrod documented how metabolic abnormalities can be traced to mutant alleles.His research was semi- nal,and in the next several decades,a large number of inherited human disorders were identified and catalogued.From this work,physicians have learned to diag- nose genetic diseases,to trace them through families,and to predict the chances that particular individuals might inherit them.Today some hospitals have professionals known as genetic counselors who are trained to advise people about the risks of inherit- ing or transmitting genetic diseases.We will discuss some aspects of genetic counsel- ing in Chapter 3. Genetic diseases like the ones that Garrod studied are individually rather rare in most human populations.For example,among newborns,the incidence of phenylke- tonuria,a disorder of amino acid metabolism,is only one in 10,000.However,mutant genes also contribute to more prevalent human maladies-heart disease and cancer, for example.In Chapter 22 we will explore ways of assessing genetic risks for complex traits such as the susceptibility to heart disease,and in Chapter 21 we will investigate the genetic basis of cancer. Advances in molecular genetics are providing new ways of detecting mutant genes in individuals.Diagnostic tests based on analysis of DNA are now readily available. For example,a hospital lab can test a blood sample or a cheek swab for the presence of a mutant allele of the BRCAI gene,which strongly predisposes its carriers to develop breast cancer.If a woman carries the mutant allele,she may be advised to undergo a mastectomy to prevent breast cancer from occurring.The application of these new molecular genetic technologies therefore often raises difficult issues for the people involved. Molecular genetics is also providing new ways to treat diseases.For decades diabetics had to be given insulin obtained from animals-usually pigs.Today,perfect human insulin is manufactured in bacterial cells that carry the human insulin gene. Vats of these cells are grown to produce the insulin polypeptide on an industrial scale.Human growth hormone,previously isolated from cadavers,is also manufac- tured in bacterial cells.This hormone is used to treat children who cannot make
14 Chapter 1 The Science of Genetics Bacillus thuringiensis. This gene encodes a protein that is toxic to many insects. Corn strains that carry the gene for BT toxin are resistant to attacks by the European corn borer, an insect that has caused enormous damage in the past ( Figure 1.13). Thus, BT corn plants produce their own insecticide. The development and use of GMOs has stirred up controversy worldwide. For example, African and European countries have been reluctant to grow BT corn or to purchase BT corn grown in the United States. Their reluctance is due to several factors, including the confl icting interests of small farmers and large agricultural corporations, and concerns about the safety of consuming genetically modifi ed food. There is also a concern that BT corn might kill nonpest species of insects such as butterfl ies and honeybees. Advances in molecular genetics have provided the tools and the materials to change agriculture profoundly. Today, policy makers are wrestling with the implications of these new technologies. GENETICS IN MEDICINE Classical genetics has provided physicians with a long list of diseases that are caused by mutant genes. The study of these diseases began shortly after Mendel’s work was rediscovered. In 1909 Sir Archibald Garrod, a British physician and biochemist, published a book entitled Inborn Errors of Metabolism. In this book Garrod documented how metabolic abnormalities can be traced to mutant alleles. His research was seminal, and in the next several decades, a large number of inherited human disorders were identifi ed and catalogued. From this work, physicians have learned to diagnose genetic diseases, to trace them through families, and to predict the chances that particular individuals might inherit them. Today some hospitals have professionals known as genetic counselors who are trained to advise people about the risks of inheriting or transmitting genetic diseases. We will discuss some aspects of genetic counseling in Chapter 3. Genetic diseases like the ones that Garrod studied are individually rather rare in most human populations. For example, among newborns, the incidence of phenylketonuria, a disorder of amino acid metabolism, is only one in 10,000. However, mutant genes also contribute to more prevalent human maladies—heart disease and cancer, for example. In Chapter 22 we will explore ways of assessing genetic risks for complex traits such as the susceptibility to heart disease, and in Chapter 21 we will investigate the genetic basis of cancer. Advances in molecular genetics are providing new ways of detecting mutant genes in individuals. Diagnostic tests based on analysis of DNA are now readily available. For example, a hospital lab can test a blood sample or a cheek swab for the presence of a mutant allele of the BRCA1 gene, which strongly predisposes its carriers to develop breast cancer. If a woman carries the mutant allele, she may be advised to undergo a mastectomy to prevent breast cancer from occurring. The application of these new molecular genetic technologies therefore often raises diffi cult issues for the people involved. Molecular genetics is also providing new ways to treat diseases. For decades diabetics had to be given insulin obtained from animals—usually pigs. Today, perfect human insulin is manufactured in bacterial cells that carry the human insulin gene. Vats of these cells are grown to produce the insulin polypeptide on an industrial scale. Human growth hormone, previously isolated from cadavers, is also manufactured in bacterial cells. This hormone is used to treat children who cannot make (a) (b) FIGURE 1.13 Use of a genetically modified plant in agriculture. (a) European corn borer eating away the stalk of a corn plant. (b) Side-by-side comparison of corn stalks from plants that are resistant (top) and susceptible (bottom) to the corn borer. The resistant plant is expressing a gene for an insecticidal protein derived from Bacillus thuringiensis.
Genetics in the World:Applications of Genetics to Human Endeavors 15 sufficient amounts of the hormone themselves because they carry a mutant allele of the growth hormone gene.Without the added hormone,these children would be affected with dwarfism.Many other medically important proteins are now routinely produced in bacterial cells that have been supplied with the appropriate human gene. The large-scale production of such proteins is one facet of the burgeoning biotech- nology industry.We will explore ways of producing human proteins in bacterial cells in Chapter 16. Human gene therapy is another way in which molecular genetic technologies are used to treat diseases.The strategy in this type of therapy is to insert a healthy,func- tional copy of a particular gene into the cells of an individual who carries only mutant copies of that gene.The inserted gene can then compensate for the faulty genes that the individual inherited.To date,human gene therapy has had mixed results.Ef- forts to cure individuals with cystic fibrosis(CF),a serious respiratory disorder,by introducing copies of the normal CF gene into lung cells have not been successful. However,medical geneticists have had some success in treating immune system and blood cell disorders by introducing the appropriate normal genes into bone marrow cells,which later differentiate into immune cells and blood cells.We will discuss the emerging technologies for human gene therapy and some of the risks involved in Chapter 16. GENETICS IN SOCIETY Modern societies depend heavily on the technology that emerges from research in the basic sciences.Our manufacturing and service industries are built on technologies for mass production,instantaneous communication,and prodigious information process- ing.Our lifestyles also depend on these technologies.At a more fundamental level, modern societies rely on technology to provide food and health care.We have already seen how genetics is contributing to these important needs.However,genetics impacts society in other ways too. One way is economic.Discoveries from genetic research have initiated count- less business ventures in the biotechnology industry.Companies that market phar- maceuticals and diagnostic tests,or that provide services such as DNA profiling, have contributed to worldwide economic growth.Another way is legal.DNA se- quences differ among individuals,and by analyzing these differences,people can be identified uniquely.Such analyses are now routinely used in many situations-to test for paternity,to convict the guilty and to exonerate the innocent of crimes for which they are accused,to authenticate claims to inheritances,and to identify the dead.Evidence based on analysis of DNA is now commonplace in courtrooms all over the world. But the impact of genetics goes beyond the material,commercial,and legal as- pects of our societies.It strikes the very core of our existence because,after all, DNA-the subject of genetics-is a crucial part of us.Discoveries from genetics raise deep,difficult,and sometimes disturbing existential questions.Who are we? Where do we come from?Does our genetic makeup determine our nature?our tal- ents?our ability to learn?our behavior?Does it play a role in setting our customs? Does it affect the ways we organize our societies?Does it influence our attitudes toward other people?Will knowledge about our genes and how they influence us affect our ideas about morality and justice,innocence and guilt,freedom and re- sponsibility?Will this knowledge change how we think about what it means to be human?Whether we like it or not,these and other probing questions await us in the not-so-distant future. Discoveries in genetics are cbanging procedures and practices in agriculture and medicine. KEY POINTS Advances in genetics are raising ethical,legal,political,social,and philosopbical questions
Genetics in the World: Applications of Genetics to Human Endeavors 15 suffi cient amounts of the hormone themselves because they carry a mutant allele of the growth hormone gene. Without the added hormone, these children would be affected with dwarfi sm. Many other medically important proteins are now routinely produced in bacterial cells that have been supplied with the appropriate human gene. The large-scale production of such proteins is one facet of the burgeoning biotechnology industry. We will explore ways of producing human proteins in bacterial cells in Chapter 16. Human gene therapy is another way in which molecular genetic technologies are used to treat diseases. The strategy in this type of therapy is to insert a healthy, functional copy of a particular gene into the cells of an individual who carries only mutant copies of that gene. The inserted gene can then compensate for the faulty genes that the individual inherited. To date, human gene therapy has had mixed results. Efforts to cure individuals with cystic fi brosis (CF), a serious respiratory disorder, by introducing copies of the normal CF gene into lung cells have not been successful. However, medical geneticists have had some success in treating immune system and blood cell disorders by introducing the appropriate normal genes into bone marrow cells, which later differentiate into immune cells and blood cells. We will discuss the emerging technologies for human gene therapy and some of the risks involved in Chapter 16. GENETICS IN SOCIETY Modern societies depend heavily on the technology that emerges from research in the basic sciences. Our manufacturing and service industries are built on technologies for mass production, instantaneous communication, and prodigious information processing. Our lifestyles also depend on these technologies. At a more fundamental level, modern societies rely on technology to provide food and health care. We have already seen how genetics is contributing to these important needs. However, genetics impacts society in other ways too. One way is economic. Discoveries from genetic research have initiated countless business ventures in the biotechnology industry. Companies that market pharmaceuticals and diagnostic tests, or that provide services such as DNA profi ling, have contributed to worldwide economic growth. Another way is legal. DNA sequences differ among individuals, and by analyzing these differences, people can be identifi ed uniquely. Such analyses are now routinely used in many situations—to test for paternity, to convict the guilty and to exonerate the innocent of crimes for which they are accused, to authenticate claims to inheritances, and to identify the dead. Evidence based on analysis of DNA is now commonplace in courtrooms all over the world. But the impact of genetics goes beyond the material, commercial, and legal aspects of our societies. It strikes the very core of our existence because, after all, DNA—the subject of genetics—is a crucial part of us. Discoveries from genetics raise deep, diffi cult, and sometimes disturbing existential questions. Who are we? Where do we come from? Does our genetic makeup determine our nature? our talents? our ability to learn? our behavior? Does it play a role in setting our customs? Does it affect the ways we organize our societies? Does it infl uence our attitudes toward other people? Will knowledge about our genes and how they infl uence us affect our ideas about morality and justice, innocence and guilt, freedom and responsibility? Will this knowledge change how we think about what it means to be human? Whether we like it or not, these and other probing questions await us in the not-so-distant future. Discoveries in genetics are changing procedures and practices in agriculture and medicine. Advances in genetics are raising ethical, legal, political, social, and philosophical questions. KEY POINTS
16 Chapter 1 The Science of Genetics Basic Exercises lllustrate Basic Genetic Analysis 1. How is genetic information expressed in cells? 2. What is the evolutionary significance of mutation? Answer:The genetic information is encoded in sequences in the Answer:Mutation creates variation in the DNA sequences of DNA.Initially,these sequences are used to synthesize RNA genes(and in the nongenic components of genomes as complementary to them-a process called transcription- well).This variation accumulates in populations of organ- and then the RNA is used as a template to specify the incor- isms over time and may eventually produce observable dif- poration of amino acids in the sequence of a polypeptide- ferences among the organisms.One population may come a process called translation.Each amino acid in the poly- to differ from another according to the kinds of mutations peptide corresponds to a sequence of three nucleotides in that have accumulated over time.Thus,mutation provides the DNA.The triplets of nucleotides that encode the dif- the input for different evolutionary outcomes at the popu- ferent amino acids are called codons. lation level. Testing Your Knowledge Integrate Different Concepts and Techniques 1. Suppose a gene contains 10 codons.How many cod- Answer:The gene possesses 30 coding nucleotides.Its polypep- ing nucleotides does the gene contain?How many tide product is expected to contain 10 amino acids,each amino acids are expected to be present in its polypep- corresponding to one of the codons in the gene.If each tide product?Among all possible genes composed of codon can specify one of 20 naturally occurring amino ac- 10 codons,how many different polypeptides could be ids,among all possible gene sequences 10 codons long,we produced? can imagine a total of 2010 polypeptide products-a truly enormous number! Questions and Problems Enhance Understanding and Develop Analytical Skills 1.1 In a few sentences,what were Mendel's key ideas about 1.9 RNA is synthesized using DNA as a template.Is DNA ever inheritance? synthesized using RNA as a template?Explain. 1.2 Both DNA and RNA are composed of nucleotides.What 1.10 The gene for a-globin is present in all vertebrate species. molecules combine to form a nucleotide? Over millions of years,the DNA sequence of this gene has 1.3 Which bases are present in DNA?Which bases are present in changed in the lineage of each species.Consequently,the RNA?Which sugars are present in each of these nucleic acids? amino acid sequence of o-globin has also changed in these lineages.Among the 141 amino acid positions in this poly- 1.4 What is a genome? peptide,human a-globin differs from shark o-globin in 79 1.5 The sequence of a strand of DNA is ATTGCCGTC.If positions;it differs from carp o-globin in 68 and from cow this strand serves as the template for DNA synthesis,what o-globin in 17.Do these data suggest an evolutionary phy- will be the sequence of the newly synthesized strand? logeny for these vertebrate species? 1.6 A gene contains 141 codons.How many nucleotides 1.11 Sickle-cell disease is caused by a mutation in one of the codons are present in the gene's coding sequence?How many in the gene for B-globin;because of this mutation the sixth amino acids are expected to be present in the polypeptide amino acid in the B-globin polypeptide is a valine instead of encoded by this gene? a glutamic acid.A less severe disease is caused by a mutation 1.7 The template strand of a gene being transcribed is that changes this same codon to one specifying lysine as the CTTGCCAGT.What will be the sequence of the RNA sixth amino acid in the B-globin polypeptide.What word is made from this template? used to describe the two mutant forms of this gene?Do you think that an individual carrying these two mutant forms of 1.8 What is the difference between transcription and translation? the B-globin gene would suffer from anemia?Explain
16 Chapter 1 The Science of Genetics Illustrate Basic Genetic Analysis Basic Exercises 1. How is genetic information expressed in cells? Answer: The genetic information is encoded in sequences in the DNA. Initially, these sequences are used to synthesize RNA complementary to them—a process called transcription— and then the RNA is used as a template to specify the incorporation of amino acids in the sequence of a polypeptide— a process called translation. Each amino acid in the polypeptide corresponds to a sequence of three nucleotides in the DNA. The triplets of nucleotides that encode the different amino acids are called codons. 2. What is the evolutionary signifi cance of mutation? Answer: Mutation creates variation in the DNA sequences of genes (and in the nongenic components of genomes as well). This variation accumulates in populations of organisms over time and may eventually produce observable differences among the organisms. One population may come to differ from another according to the kinds of mutations that have accumulated over time. Thus, mutation provides the input for different evolutionary outcomes at the population level. Testing Your Knowledge Integrate Different Concepts and Techniques 1. Suppose a gene contains 10 codons. How many coding nucleotides does the gene contain? How many amino acids are expected to be present in its polypeptide product? Among all possible genes composed of 10 codons, how many different polypeptides could be produced? Answer: The gene possesses 30 coding nucleotides. Its polypeptide product is expected to contain 10 amino acids, each corresponding to one of the codons in the gene. If each codon can specify one of 20 naturally occurring amino acids, among all possible gene sequences 10 codons long, we can imagine a total of 2010 polypeptide products—a truly enormous number! 1.1 In a few sentences, what were Mendel’s key ideas about inheritance? 1.2 Both DNA and RNA are composed of nucleotides. What molecules combine to form a nucleotide? 1.3 Which bases are present in DNA? Which bases are present in RNA? Which sugars are present in each of these nucleic acids? 1.4 What is a genome? 1.5 The sequence of a strand of DNA is ATTGCCGTC. If this strand serves as the template for DNA synthesis, what will be the sequence of the newly synthesized strand? 1.6 A gene contains 141 codons. How many nucleotides are present in the gene’s coding sequence? How many amino acids are expected to be present in the polypeptide encoded by this gene? 1.7 The template strand of a gene being transcribed is CTTGCCAGT. What will be the sequence of the RNA made from this template? 1.8 What is the difference between transcription and translation? 1.9 RNA is synthesized using DNA as a template. Is DNA ever synthesized using RNA as a template? Explain. 1.10 The gene for -globin is present in all vertebrate species. Over millions of years, the DNA sequence of this gene has changed in the lineage of each species. Consequently, the amino acid sequence of -globin has also changed in these lineages. Among the 141 amino acid positions in this polypeptide, human -globin differs from shark -globin in 79 positions; it differs from carp -globin in 68 and from cow -globin in 17. Do these data suggest an evolutionary phylogeny for these vertebrate species? 1.11 Sickle-cell disease is caused by a mutation in one of the codons in the gene for -globin; because of this mutation the sixth amino acid in the -globin polypeptide is a valine instead of a glutamic acid. A less severe disease is caused by a mutation that changes this same codon to one specifying lysine as the sixth amino acid in the -globin polypeptide. What word is used to describe the two mutant forms of this gene? Do you think that an individual carrying these two mutant forms of the -globin gene would suffer from anemia? Explain. Questions and Problems Enhance Understanding and Develop Analytical Skills
Questions and Problems 17 1.12 Hemophilia is an inherited disorder in which the blood- purified from blood donations.This factor is a protein clotting mechanism is defective.Because of this defect, encoded by a human gene.Suggest a way in which mod- people with hemophilia may die from cuts or bruises, ern genetic technology could be used to produce this especially if internal organs such as the liver,lungs,or factor on an industrial scale.Is there a way in which the kidneys have been damaged.One method of treatment inborn error of hemophilia could be corrected by human involves injecting a blood-clotting factor that has been gene therapy? Genomics on the Web at http://www.ncbi.nlm.nih.gov You might enjoy using the NCBI web site to explore the Links to get to the National Human Genome Research Insti- Human Genome Project.Click on More about NCBI and then tute's page.Once there,click on Education to bring up material on Outreach and Education.From there click on Recommended on the Human Genome Project
Questions and Problems 17 1.12 Hemophilia is an inherited disorder in which the bloodclotting mechanism is defective. Because of this defect, people with hemophilia may die from cuts or bruises, especially if internal organs such as the liver, lungs, or kidneys have been damaged. One method of treatment involves injecting a blood-clotting factor that has been purifi ed from blood donations. This factor is a protein encoded by a human gene. Suggest a way in which modern genetic technology could be used to produce this factor on an industrial scale. Is there a way in which the inborn error of hemophilia could be corrected by human gene therapy? You might enjoy using the NCBI web site to explore the Human Genome Project. Click on More about NCBI and then on Outreach and Education. From there click on Recommended Links to get to the National Human Genome Research Institute’s page. Once there, click on Education to bring up material on the Human Genome Project. Genomics on the Web at http://www.ncbi.nlm.nih.gov