Introduction to Genetics PDF

1 Introduction to Genetics ALBINISM IN THE HOPIS R ising a thousand feet above the desert floor, Black Mesa...

1 Introduction to Genetics ALBINISM IN THE HOPIS R ising a thousand feet above the desert floor, Black Mesa dominates the horizon of the Enchanted Desert and provides a familiar landmark for travelers passing through northeastern Arizona. Not only is Black Mesa a prominent geologic feature, but, more significantly, it is the ancestral home of the Hopi Native Americans. Fingers of the mesa reach out into the desert, and alongside or on top of each finger is a Hopi village. Most of the villages are quite small, having only a few dozen inhabitants, but they are incredibly old. One village, Oraibi, has existed on Black Mesa since 1150 a.d. and is the oldest continuously occupied settle- ment in North America. In 1900, Alěs Hrdliěka, an anthropologist and physician working for the American Museum of Natural History, vis- ited the Hopi villages of Black Mesa and reported a startling discovery. Among the Hopis were 11 white persons—not Caucasians, but actually white Hopi Native Americans. Hopi bowl, early twentieth century. Albinism, a genetic condition, arises with These persons had a genetic condition known as albinism high frequency among the Hopi people and occupies a special place in the Hopi (Figure 1.1). culture. [The Newark Museum/Art Resource, NY.] Albinism is caused by a defect in one of the enzymes required to produce melanin, the pigment that darkens our skin, hair, and eyes. People with albinism don’t produce melanin or they produce only small amounts of it and, consequently, have white hair, light skin, and no pigment in the irises of their eyes. Melanin normally protects the DNA of skin cells from the damaging effects of ultraviolet radiation in sunlight, and melanin’s presence in the developing eye is essential for proper eyesight. The genetic basis of albinism was first described by the English physician Archibald Garrod, who recognized in 1908 that the condition was inherited as an autosomal recessive trait, meaning that a person must receive two copies of an albino mutation—one from each parent—to have albinism. In recent years, the molecular natures of the mutations that lead to albinism have been elucidated. Albinism in humans is caused by defects in any one of several different genes that control the synthesis and storage of melanin; many different types of mutations can occur at each gene, any one of which may lead to albinism. The form of albinism found in the Hopis is most likely oculocutaneous albinism type 2, due to a defect in the OCA2 gene on chromosome 15. The Hopis are not unique in having albinos among the members of their tribe. Albinism is found in almost all human ethnic groups and is described in ancient writings; it has probably been present since humankind’s beginnings. What is unique about the 1 2 Chapter 1 Hopis is the high frequency of albinism. In most human groups, albinism is rare, present in only about 1 in 20,000 persons. In the villages on Black Mesa, it reaches a frequency of 1 in 200, a hundred times as frequent as in most other populations. Why is albinism so frequent among the Hopi Native Americans? The answer to this question is not completely known, but geneticists who have studied albinism in the Hopis speculate that the high frequency of the albino gene is related to the special place that albi- nism occupied in the Hopi culture. For much of their history, the Hopis considered mem- bers of their tribe with albinism to be important and special. People with albinism were considered pretty, clean, and intelligent. Having a number of people with albinism in one’s village was considered a good sign, a symbol that the people of the village contained par- 1.1 Albinism among the Hopi Native ticularly pure Hopi blood. Albinos performed in Hopi ceremonies and assumed positions Americans. In this photograph, taken about of leadership within the tribe, often becoming chiefs, healers, and religious leaders. 1900, the Hopi girl in the center has albinism. Hopi albinos were also given special treatment in everyday activities. The Hopis [The Field Museum/Charles Carpenter.] farmed small garden plots at the foot of Black Mesa for centuries. Every day throughout the growing season, the men of the tribe trekked to the base of Black Mesa and spent much of the day in the bright southwestern sunlight tending their corn and vegetables. With little or no melanin pigment in their skin, people with albinism are extremely susceptible to sun- burn and have increased incidences of skin cancer when exposed to the sun. Furthermore, many don’t see well in bright sunlight. But the male Hopis with albinism were excused from this normal male labor and allowed to remain behind in the village with the women of the tribe, performing other duties. Geneticists have suggested that these special considerations given to albino members of the tribe are partly responsible for the high frequency of albinism among the Hopis. Throughout the growing season, the albino men were the only male members of the tribe in the village during the day with all the women and, thus, they enjoyed a mating advan- tage, which helped to spread their albino genes. In addition, the special considerations given to albino Hopis allowed them to avoid the detrimental effects of albinism—increased skin cancer and poor eyesight. The small size of the Hopi tribe probably also played a role by allowing chance to increase the frequency of the albino gene. Regardless of the factors that led to the high frequency of albinism, the Hopis clearly respected and valued the mem- bers of their tribe who possessed this particular trait. Unfortunately, people with genetic conditions in many societies are often subject to discrimination and prejudice. TRY PROBLEMS 1 AND 25 G enetics is one of the most rapidly advancing fields of science, with important new discoveries reported every month. Pick up almost any major newspaper or news genetics to each of us, to society at large, and to students of biology. We then turn to the history of genetics, how the field as a whole developed. The final part of the chapter presents magazine and chances are that you will see articles related some fundamental terms and principles of genetics that are to genetics: the completion of another genome, such as that used throughout the book. of the platypus; the discovery of genes that affect major dis- eases, including multiple sclerosis, depression, and cancer; a report of DNA analyzed from long-extinct animals such 1.1 Genetics Is Important to Us as the woolly mammoth; and the identification of genes Individually, to Society, and to that affect skin pigmentation, height, and learning ability in humans. Even among the advertisements, one is likely to see the Study of Biology genetics: ads for genetic testing to determine paternity, one’s Albinism among the Hopis illustrates the important role ancestry, and susceptibility to diseases and disorders. These that genes play in our lives. This one genetic defect, among new findings and applications of genetics often have signifi- the 20,000 genes that humans possess, completely changes cant economic and ethical implications, making the study of the life of a Hopi who possesses it. It alters his or her genetics relevant, timely, and interesting. occupation, role in Hopi society, and relations with other This chapter introduces you to genetics and reviews members of the tribe. We all possess genes that influence some concepts that you may have encountered briefly in a our lives in significant ways. Genes affect our height, weight, biology course. We begin by considering the importance of hair color, and skin pigmentation. They affect our suscepti- (a) (b) Introduction to Genetics 3 Laron dwarfism Susceptibility to diphtheria Low-tone deafness Limb–girdle muscular Diastrophic dystrophy dysplasia Chromosome 5 1.3 In the Green Revolution, genetic techniques were used to 1.2 Genes influence susceptibility to many diseases and develop new high-yielding strains of crops. (Left) Norman Borlaug, disorders. (a) An X-ray of the hand of a person suffering from a leader in the development of new strains of wheat that led to the diastrophic dysplasia (bottom), a hereditary growth disorder that Green Revolution. Borlaug was awarded the Nobel Peace Prize in results in curved bones, short limbs, and hand deformities, compared 1970. (Right) Modern, high-yielding rice plant (left) and traditional rice with an X-ray of a normal hand (top). (b) This disorder is due to a plant (right). [Left: UPI/Corbis-Bettman. Right: IRRI.] defect in a gene on chromosome 5. Braces indicate regions on chromosome 5 where genes giving rise to other disorders are located. [Part a: (top) Biophoto Associates/Science Source/Photo Researchers; also been used to produce bacteria that remove minerals (bottom) courtesy of Eric Lander, Whitehead Institute, MIT.] from ore, break down toxic chemicals, and inhibit damaging frost formation on crop plants. Genetics plays a critical role in medicine. Physicians bility to many diseases and disorders (Figure 1.2) and even recognize that many diseases and disorders have a hereditary contribute to our intelligence and personality. Genes are component, including rare genetic disorders such as sickle- fundamental to who and what we are. cell anemia and Huntington disease as well as many com- Although the science of genetics is relatively new mon diseases such as asthma, diabetes, and hypertension. compared with sciences such as astronomy and chemistry, Advances in genetics have resulted in important insights into people have understood the hereditary nature of traits and the nature of diseases such as cancer and in the development have practiced genetics for thousands of years. The rise of agriculture began when people started to apply genetic principles to the domestication of plants and animals. Today, the major crops and animals used in agriculture are quite different from their wild progenitors, having undergone extensive genetic alterations that increase their yields and provide many desirable traits, such as disease and pest resis- tance, special nutritional qualities, and characteristics that facilitate harvest. The Green Revolution, which expanded food production throughout the world in the 1950s and 1960s, relied heavily on the application of genetics (Figure 1.3). Today, genetically engineered corn, soybeans, and other crops constitute a significant proportion of all the food pro- duced worldwide. The pharmaceutical industry is another area in which genetics plays an important role. Numerous drugs and food additives are synthesized by fungi and bacteria that have been genetically manipulated to make them efficient producers of these substances. The biotechnology industry employs molecular genetic techniques to develop and mass- produce substances of commercial value. Growth hormone, 1.4 The biotechnology industry uses molecular genetic insulin, and clotting factor are now produced commercially methods to produce substances of economic value. by genetically engineered bacteria (Figure 1.4). Genetics has [Andrew Brooks/Corbis.] 4 Chapter 1 of diagnostic tests such as those that identify pathogens and tions, the code words are identical. Likewise, the process by defective genes. Gene therapy—the direct alteration of genes which genetic information is copied and decoded is remark- to treat human diseases—has now been administered to ably similar for all forms of life. These common features of thousands of patients. heredity suggest that all life on Earth evolved from the same primordial ancestor that arose between 3.5 billion and 4 bil- lion years ago. Biologist Richard Dawkins describes life as a The Role of Genetics in Biology river of DNA that runs through time, connecting all organ- Although an understanding of genetics is important to all isms past and present. people, it is critical to the student of biology. Genetics pro- That all organisms have similar genetic systems means vides one of biology’s unifying principles: all organisms use that the study of one organism’s genes reveals principles that genetic systems that have a number of features in common. apply to other organisms. Investigations of how bacterial Genetics also undergirds the study of many other biological DNA is copied (replicated), for example, provide informa- disciplines. Evolution, for example, is genetic change taking tion that applies to the replication of human DNA. It also place through time; so the study of evolution requires an means that genes will function in foreign cells, which makes understanding of genetics. Developmental biology relies genetic engineering possible. Unfortunately, these similar heavily on genetics: tissues and organs develop through the genetic systems are also the basis for diseases such as AIDS regulated expression of genes (Figure 1.5). Even such fields (acquired immune deficiency syndrome), in which viral as taxonomy, ecology, and animal behavior are making genes are able to function—sometimes with alarming effi- increasing use of genetic methods. The study of almost any ciency—in human cells. field of biology or medicine is incomplete without a thor- Life’s diversity and adaptation are products of evolution, ough understanding of genes and genetic methods. which is simply genetic change through time. Evolution is a two-step process: first, inherited differences arise randomly and, then, the proportion of individuals with particular dif- Genetic Diversity and Evolution ferences increases or decreases. Genetic variation is therefore Life on Earth exists in a tremendous array of forms and fea- the foundation of all evolutionary change and is ultimately tures in almost every conceivable environment. Life is also the basis of all life as we know it. Furthermore, techniques characterized by adaptation: many organisms are exquisitely of molecular genetics are now routinely used to decipher suited to the environment in which they are found. The his- evolutionary relationships among organisms; for example, tory of life is a chronicle of new forms of life emerging, old recent analysis of DNA isolated from Neanderthal fossils forms disappearing, and existing forms changing. has yielded new information concerning the relationship Despite their tremendous diversity, living organisms between Neanderthals and modern humans. Genetics, the have an important feature in common: all use similar study of genetic variation, is critical to understanding the genetic systems. A complete set of genetic instructions for past, present, and future of life. TRY PROBLEM 17 any organism is its genome, and all genomes are encoded in nucleic acids—either DNA or RNA. The coding system for genomic information also is common to all life: genetic CONCEPTS instructions are in the same format and, with rare excep- Heredity affects many of our physical features as well as our sus- ceptibility to many diseases and disorders. Genetics contributes to advances in agriculture, pharmaceuticals, and medicine and is fundamental to modern biology. All organisms use similar genetic systems, and genetic variation is the foundation of the diversity of all life. ✔ CONCEPT CHECK 1 What are some of the implications of all organisms having similar genetic systems? a. That all life forms are genetically related b. That research findings on one organism’s gene function can often be applied to other organisms 1.5 The key to development lies in the regulation of gene expression. This early fruit-fly embryo illustrates the localized c. That genes from one organism can often exist and thrive in expression of the engrailed gene, which helps determine the another organism development of body segments in the adult fly. [Stephen Paddock d. All of the above Digital Image Gallery.]  Introduction to Genetics 5 Divisions of Genetics and with the passage of time. Because evolution is genetic change, population genetics is fundamentally the study of The study of genetics consists of three major subdisciplines: evolution. The focus of population genetics is the group of transmission genetics, molecular genetics, and population genes found in a population. genetics (Figure 1.6). Also known as classical genetics, Division of the study of genetics into these three groups transmission genetics encompasses the basic principles is convenient and traditional, but we should recognize of heredity and how traits are passed from one genera- that the fields overlap and that each major subdivision tion to the next. This area addresses the relation between can be further divided into a number of more-specialized chromosomes and heredity, the arrangement of genes on fields, such as chromosomal genetics, biochemical genetics, chromosomes, and gene mapping. Here, the focus is on the quantitative genetics, and so forth. Alternatively, genetics individual organism—how an individual organism inherits can be subdivided by organism (fruit fly, corn, or bacterial its genetic makeup and how it passes its genes to the next genetics), and each of these organisms can be studied at the generation. level of transmission, molecular, and population genetics. Molecular genetics concerns the chemical nature of the Modern genetics is an extremely broad field, encompass- gene itself: how genetic information is encoded, replicated, ing many interrelated subdisciplines and specializations. and expressed. It includes the cellular processes of replica- TRY PROBLEM 18 tion, transcription, and translation (by which genetic infor- mation is transferred from one molecule to another) and gene regulation (the processes that control the expression of Model Genetic Organisms genetic information). The focus in molecular genetics is the Through the years, genetic studies have been conducted on gene, its structure, organization, and function. thousands of different species, including almost all major Population genetics explores the genetic composition groups of bacteria, fungi, protists, plants, and animals. of groups of individual members of the same species (popu- Nevertheless, a few species have emerged as model genetic lations) and how that composition changes geographically organisms—organisms having characteristics that make them particularly useful for genetic analysis and about (a) (b) which a tremendous amount of genetic information has accumulated. Six model organisms that have been the sub- ject of intensive genetic study are: Drosophila melanogaster, the fruit fly; Escherichia coli, a bacterium present in the gut of humans and other mammals; Caenorhabditis elegans, a nematode worm; Arabidopsis thaliana, the thale-cress plant; Mus musculus, the house mouse; and Saccharomyces cerevisiae, baker’s yeast (Figure 1.7). These species are the organisms of choice for many genetic researchers, and their genomes were sequenced as a part of the Human Genome Project. The life cyles and genetic characteristics of these Transmission Molecular genetics genetics model genetic organisms are described in more detail in the Guide to Model Genetic Organisms located at the end of the book. Population At first glance, this group of lowly and sometimes genetics despised creatures might seem unlikely candidates for model organisms. However, all possess life cycles and traits that make them particularly suitable for genetic study, including a short generation time, large but manageable numbers of progeny, adaptability to a laboratory environment, and the (c) ability to be housed and propagated inexpensively. Other species that are frequently the subjects of genetic research and considered genetic models include Neurospora crassa (bread mold), Zea mays (corn), Danio rerio (zebrafish), and Xenopus laevis (clawed frog). Although not generally consid- 1.6 Genetics can be subdivided into three interrelated fields. ered a genetic model, humans also have been subjected to [Top left: Junior’s Bildarchiv/Alamy. Top right: Mona file M0214602tif. intensive genetic scrutiny; special techniques for the genetic Bottom: J. Alcock/Visuals Unlimited.] analysis of humans are discussed in Chapter 6. 6 Chapter 1 (a) (b) (c) Drosophila melanogaster Escherichia coli Caenorhabditis elegans Fruit fly Bacterium Nematode 1.7 Model genetic organisms are species having features that make them useful for genetic analysis. [Part a: SPL/Photo Researchers. Part b: Gary Gaugler/Visuals Unlimited. Part c: Natalie Pujol/Visuals Unlimited. Part d: Peggy Greb/ARS. Part e: Joel Page/AP. Part f: T. E. Adams/Visuals Unlimited.] The value of model genetic organisms is illustrated by the in the laboratory, they isolated and sequenced the gene use of zebrafish to identify genes that affect skin pigmentation responsible for the golden mutation and found that it in humans. For many years, geneticists have recognized that encodes a protein that takes part in calcium uptake by differences in pigmentation among human ethnic groups are melanosomes. They then searched a database of all known genetic (Figure 1.8a), but the genes causing these differences human genes and found a similar gene called SLC24A5, were largely unknown. The zebrafish has recently become an which encodes the same function in human cells. When important model in genetic studies because it is a small verte- they examined human populations, they found that light- brate that produces many offspring and is easy to rear in the skinned Europeans typically possessed one form of this laboratory. The mutant zebrafish called golden has light pig- gene, whereas darker-skinned Africans, Eastern Asians, mentation due to the presence of fewer, smaller, and less-dense and Native Americans usually possessed a different form pigment-containing structures called melanosomes in its cells of the gene. Many other genes also affect pigmentation in (Figure 1.8b). Light skin in humans is similarly due to fewer humans, as illustrated by mutations in the OCA2 gene that and less-dense melanosomes in pigment-containing cells. produce albinism among the Hopi Native Americans (dis- Keith Cheng and his colleagues at Pennsylvania State cussed in the introduction to this chapter). Nevertheless, University College of Medicine hypothesized that light SLC24A5 appears to be responsible for 24% to 38% of skin in humans might result from a mutation that is the differences in pigmentation between Africans and similar to the golden mutation in zebrafish. Taking advan- Europeans. This example illustrates the power of model tage of the ease with which zebrafish can be manipulated organisms in genetic research. (a) 1.8 The zebrafish, a genetic model organism, has been instrumental in helping to identify genes encoding pigmentation (b) differences among humans. (a) Human ethnic groups differ in degree of skin pigmentation. (b) The zebrafish golden mutation is caused by a gene that controls the amount of melanin pigment in melanosomes. [Part a: PhotoDisc. Part b: K. Cheng/J. Gittlen, Cancer Research Foundation, Pennsylvania State College of Normal zebrafish Golden mutant Medicine.]  Introduction to Genetics 7 (d) (e) (f) Arabidopsis thaliana Mus musculus Saccharomyces cerevisiae Thale-cress plant House mouse Baker’s yeast CONCEPTS 1.2 Humans Have Been Using The three major divisions of genetics are transmission genetics, Genetics for Thousands of Years molecular genetics, and population genetics. Transmission genet- ics examines the principles of heredity; molecular genetics deals Although the science of genetics is young—almost entirely a with the gene and the cellular processes by which genetic infor- product of the past 100 years or so—people have been using mation is transferred and expressed; population genetics concerns genetic principles for thousands of years. the genetic composition of groups of organisms and how that composition changes geographically and with the passage of time. The Early Use and Understanding of Heredity Model genetic organisms are species that have received special The first evidence that people understood and applied emphasis in genetic research; they have characteristics that make them useful for genetic analysis. the principles of heredity in earlier times is found in the domestication of plants and animals, which began between ✔ CONCEPT CHECK 2 approximately 10,000 and 12,000 years ago in the Middle East. The first domesticated organisms included wheat, peas, Would the horse make a good model genetic organism? Why or lentils, barley, dogs, goats, and sheep (Figure 1.9a). By 4000 why not? years ago, sophisticated genetic techniques were already in 1.9 Ancient peoples practiced genetic techniques in agriculture. (Left) Modern wheat, with larger and more numerous seeds that do not scatter before harvest, was produced by interbreeding at least three different wild species. (Right) Assyrian bas-relief sculpture showing artificial pollination of date palms at the time of King Assurnasirpalli II, who reigned from 883 to 859 B.C. [Left: Scott Bauer/ARS/USDA. Right: The Metropolitan Museum of Art, gift of John D. Rockefeller, Jr., 1932. (32.143.3) Photograph © 1996 Metropolitan Museum of Art.] 8 Chapter 1 use in the Middle East. Assyrians and Babylonians developed Pangenesis led the ancient Greeks to propose the notion several hundred varieties of date palms that differed in fruit of the inheritance of acquired characteristics, in which traits size, color, taste, and time of ripening (Figure 1.9b). Other acquired in a person’s lifetime become incorporated into that crops and domesticated animals were developed by cultures person’s hereditary information and are passed on to offspring; in Asia, Africa, and the Americas in the same period. for example, people who developed musical ability through Ancient writings demonstrate that early humans were also diligent study would produce children who are innately aware of their own heredity. Hindu sacred writings dating to endowed with musical ability. The notion of the inheritance 2000 years ago attribute many traits to the father and suggest of acquired characteristics also is no longer accepted, but it that differences between siblings are produced by the mother. remained popular through the twentieth century. The Talmud, the Jewish book of religious laws based on oral Although the ancient Romans contributed little to an traditions dating back thousands of years, presents an uncan- understanding of human heredity, they successfully developed nily accurate understanding of the inheritance of hemophilia. It a number of techniques for animal and plant breeding; the directs that, if a woman bears two sons who die of bleeding after techniques were based on trial and error rather than any gen- circumcision, any additional sons that she bears should not be eral concept of heredity. Little new information was added to circumcised; nor should the sons of her sisters be circumcised. the understanding of genetics in the next 1000 years. This advice accurately corresponds to the X-linked pattern of Dutch eyeglass makers began to put together simple inheritance of hemophilia (discussed further in Chapter 6). microscopes in the late 1500s, enabling Robert Hooke The ancient Greeks gave careful consideration to human (1635–1703) to discover cells in 1665. Microscopes pro- reproduction and heredity. Greek philosophers developed vided naturalists with new and exciting vistas on life, and the concept of pangenesis, in which specific particles, later perhaps excessive enthusiasm for this new world of the very called gemmules, carry information from various parts of small gave rise to the idea of preformationism. According the body to the reproductive organs, from which they are to preformationism, inside the egg or sperm there exists passed to the embryo at the moment of conception (Figure a fully formed miniature adult, a homunculus, which sim- 1.10). Although incorrect, the concept of pangenesis was ply enlarges in the course of development (Figure 1.11). highly influential and persisted until the late 1800s. Preformationism meant that all traits were inherited from (a) Pangenesis concept (b) Germ-plasm theory 1 According to the pangenesis 1 According to the germ-plasm concept, genetic information theory, germ-line tissue in from different parts of the the reproductive organs… body… 2 …travels to the 2 …contains a complete set reproductive organs… of genetic information… 3 …where it is transferred 3 …that is transferred to the gametes. directly to the gametes. Sperm Sperm Zygote Zygote Egg Egg 1.10 Pangenesis, an early concept of inheritance, compared with the modern germ-plasm theory.  Introduction to Genetics 9 of the cell theory in 1839. According to this theory, all life is composed of cells, cells arise only from preexisting cells, and the cell is the fundamental unit of structure and function in living organisms. Biologists interested in heredity began to examine cells to see what took place in the course of cell reproduction. Walther Flemming (1843–1905) observed the division of chromosomes in 1879 and published a superb description of mitosis. By 1885, it was generally recognized that the nucleus contained the hereditary information. Charles Darwin (1809–1882), one of the most influ- ential biologists of the nineteenth century, put forth the theory of evolution through natural selection and published his ideas in On the Origin of Species in 1859. Darwin rec- ognized that heredity was fundamental to evolution, and he conducted extensive genetic crosses with pigeons and other organisms. However, he never understood the nature of inheritance, and this lack of understanding was a major omission in his theory of evolution. 1.11 Preformationists in the seventeenth and eighteenth In the last half of the nineteenth century, cytologists centuries believed that sperm or eggs contained fully formed humans (the homunculus). Shown here is a drawing of a demonstrated that the nucleus had a role in fertilization. homunculus inside a sperm. [Science VU/Visuals Unlimited.] Near the close of the nineteenth century, August Weismann (1834–1914) finally laid to rest the notion of the inheritance of acquired characteristics. He cut off the tails of mice for 22 only one parent—from the father if the homunculus was in consecutive generations and showed that the tail length in the sperm or from the mother if it was in the egg. Although descendants remained stubbornly long. Weismann proposed many observations suggested that offspring possess a mix- the germ-plasm theory, which holds that the cells in the ture of traits from both parents, preformationism remained reproductive organs carry a complete set of genetic informa- a popular concept throughout much of the seventeenth and tion that is passed to the egg and sperm (see Figure 1.10b). eighteenth centuries. Another early notion of heredity was blending inheri- tance, which proposed that offspring are a blend, or mixture, of parental traits. This idea suggested that the genetic material itself blends, much as blue and yellow pigments blend to make green paint. Once blended, genetic differences could not be separated out in future generations, just as green paint cannot be separated out into blue and yellow pigments. Some traits do appear to exhibit blending inheritance; however, we realize today that individual genes do not blend. The Rise of the Science of Genetics In 1676, Nehemiah Grew (1641–1712) reported that plants reproduce sexually by using pollen from the male sex cells. With this information, a number of botanists began to experiment with crossing plants and creating hybrids, including Gregor Mendel (1822–1884; Figure 1.12), who went on to discover the basic principles of heredity. Mendel’s conclusions, which were not widely known in the scientific community for 35 years, laid the foundation for our modern understanding of heredity, and he is generally recognized today as the father of genetics. Developments in cytology (the study of cells) in the 1800s had a strong influence on genetics. Robert Brown 1.12 Gregor Mendel was the founder of modern genetics. (1773–1858) described the cell nucleus in 1833. Building on Mendel first discovered the principles of heredity by crossing different the work of others, Matthias Jacob Schleiden (1804–1881) varieties of pea plants and analyzing the transmission of traits in and Theodor Schwann (1810–1882) proposed the concept subsequent generations. [Hulton Archive/Getty Images.] 10 Chapter 1 The year 1900 was a watershed in the history of genetics. Gregor Mendel’s pivotal 1866 publication on experiments with pea plants, which revealed the principles of heredity, was rediscovered, as considered in more detail in Chapter 3. The significance of his conclusions was recognized, and other biologists immediately began to conduct similar genetic studies on mice, chickens, and other organisms. The results of these investigations showed that many traits indeed follow Mendel’s rules. Some of the early concepts of heredity are summarized in Table 1.1. After the acceptance of Mendel’s theory of heredity, Walter Sutton (1877–1916) proposed in 1902 that genes, the units of inheritance, are located on chromosomes. Thomas Hunt Morgan (1866–1945) discovered the first genetic mutant of fruit flies in 1910 and used fruit flies to unravel many details 1.13 The human genome was completely sequenced in 2003. of transmission genetics. Ronald A. Fisher (1890–1962), John A chromatograph of a small portion of the human genome. [Science Museum/SSPL.] B. S. Haldane (1892–1964), and Sewall Wright (1889–1988) laid the foundation for population genetics in the 1930s by synthesizing Mendelian genetics and evolutionary theory. James Watson (b. 1928) and Francis Crick (1916–2004), along Geneticists began to use bacteria and viruses in the 1940s; with Maurice Wilkins (1916–2004) and Rosalind Franklin the rapid reproduction and simple genetic systems of these (1920–1958), described the three-dimensional structure of organisms allowed detailed study of the organization and DNA in 1953, ushering in the era of molecular genetics. structure of genes. At about this same time, evidence accu- By 1966, the chemical structure of DNA and the system mulated that DNA was the repository of genetic information. by which it determines the amino acid sequence of proteins had been worked out. Advances in molecular genetics led to the first recombinant DNA experiments in 1973, which touched off another revolution in genetic research. Walter Table 1.1 Early concepts of heredity Gilbert (b. 1932) and Frederick Sanger (b. 1918) developed methods for sequencing DNA in 1977. The polymerase chain Correct or reaction, a technique for quickly amplifying tiny amounts of Concept Proposed Incorrect DNA, was developed by Kary Mullis (b. 1944) and others in 1983. In 1990, gene therapy was used for the first time Pangenesis Genetic information Incorrect to treat human genetic disease in the United States, and the travels from different Human Genome Project was launched. By 1995, the first parts of the body to complete DNA sequence of a free-living organism—the bac- reproductive organs. terium Haemophilus influenzae—was determined, and the Inheritance of Acquired traits become Incorrect first complete sequence of a eukaryotic organism (yeast) was acquired incorporated into reported a year later. A rough draft of the human genome characteristics hereditary information. sequence was reported in 2000, with the sequence essentially Preformationism Miniature organism Incorrect completed in 2003, ushering in a new era in genetics (Figure resides in sex cells, 1.13). Today, the genomes of numerous organisms are being and all traits are sequenced, analyzed, and compared. TRY PROBLEMS 22 AND 23 inherited from one parent. The Future of Genetics Blending Genes blend and mix. Incorrect inheritance Numerous advances in genetics are being made today, and genetics remains at the forefront of biological research. Germ-plasm All cells contain a Correct theory complete set of New, rapid methods for sequencing DNA are being used to genetic information. sequence the genomes of numerous species, from bacteria to elephants, and the information content of genetics is Cell theory All life is composed Correct increasing at a rapid pace. New details about gene structure of cells, and cells arise only from cells. and function are continually expanding our knowledge of how genetic information is encoded and how it specifies Mendelian Traits are inherited Correct traits. These findings are redefining what a gene is. inheritance in accord with The power of new methods to identify and analyze genes defined principles. is illustrated by recent genetic studies of heart attacks in  Introduction to Genetics 11 humans. Physicians have long recognized that heart attacks use of genetics in agriculture will contine to improve the pro- run in families, but finding specific genes that contribute to ductivity of domestic crops and animals, helping to feed the an increased risk of a heart attack has, until recently, been dif- future world population. This ever-widening scope of genetics ficult. In 2009, an international team of geneticists examined will raise significant ethical, social, and economic issues. the DNA of 26,000 people in 10 countries for single differ- This brief overview of the history of genetics is not intend- ences in the DNA (called single-nucleotide polymorphisms, ed to be comprehensive; rather it is designed to provide a sense or SNPS) that might be associated with an increased risk of of the accelerating pace of advances in genetics. In the chapters myocardial infarction. This study and other similar studies to come, we will learn more about the experiments and the sci- identified several new genes that affect the risk of coronary entists who helped shape the discipline of genetics. artery disease and early heart attacks. These findings may make it possible to identify persons who are predisposed to CONCEPTS heart attack, allowing early intervention that might prevent Humans first applied genetics to the domestication of plants and ani- the attacks from occurring. Analyses of SNPS are helping to mals between 10,000 and 12,000 years ago. Developments in plant locate genes that affect all types of traits, from eye color and hybridization and cytology in the eighteenth and nineteenth centu- height to glaucoma and heart attacks. ries laid the foundation for the field of genetics today. After Mendel’s Information about sequence differences among organisms work was rediscovered in 1900, the science of genetics developed is also a source of new insights about evolution. For example, rapidly and today is one of the most active areas of science. recent analysis of DNA sequences at 30 genes has revealed that all living cats can trace their ancestry to a pantherlike cat living ✔ CONCEPT CHECK 3 in Southeast Asia about 11 million years ago and that all living How did developments in cytology in the nineteenth century contrib- cats can be divided into eight groups or lineages. ute to our modern understanding of genetics? In recent years, our understanding of the role of RNA in many cellular processes has expanded greatly; RNA has a role in many aspects of gene function. The discovery in 1.3 A Few Fundamental Concepts the late 1990s of tiny RNA molecules called small interfer- ing RNAs and micro RNAs led to the recognition that these Are Important for the Start of Our molecules play central roles in gene expression and develop- Journey into Genetics ment. Today, recognition of the importance of alterations Undoubtedly, you learned some genetic principles in other of DNA and chromosome structure that do not include the biology classes. Let’s take a few moments to review some base sequence of the DNA is increasing. Many such altera- fundamental genetic concepts. tions, called epigenetic changes, are stable and affect the expression of traits. New genetic microchips that simultane- Cells are of two basic types: eukaryotic and prokary- ously analyze thousands of RNA molecules are providing otic. Structurally, cells consist of two basic types, although, information about the activities of thousands of genes in a evolutionarily, the story is more complex (see Chapter 2). given cell, allowing a detailed picture of how cells respond Prokaryotic cells lack a nuclear membrane and possess no to external signals, environmental stresses, and disease states membrane-bounded cell organelles, whereas eukaryotic cells such as cancer. In the emerging field of proteomics, powerful are more complex, possessing a nucleus and membrane- computer programs are being used to model the structure bounded organelles such as chloroplasts and mitochondria. and function of proteins from DNA sequence information. All of this information provides us with a better under- The gene is the fundamental unit of heredity. The pre- standing of numerous biological processes and evolutionary cise way in which a gene is defined often varies, depending relationships. The flood of new genetic information requires on the biological context. At the simplest level, we can think the continuous development of sophisticated computer pro- of a gene as a unit of information that encodes a genetic grams to store, retrieve, compare, and analyze genetic data characteristic. We will enlarge this definition as we learn and has given rise to the field of bioinformatics, a merging more about what genes are and how they function. of molecular biology and computer science. Genes come in multiple forms called alleles. A gene that A number of companies and researchers are racing to specifies a characteristic may exist in several forms, called alleles. develop the technology for sequencing the entire genome of For example, a gene for coat color in cats may exist as an allele a single person for less than $1000. As the cost of sequencing that encodes black fur or as an allele that encodes orange fur. decreases, the focus of DNA-sequencing efforts will shift from the genomes of different species to individual differences Genes confer phenotypes. One of the most important within species. In the not-too-distant future, each person will concepts in genetics is the distinction between traits and genes. likely possess a copy of his or her entire genome sequence, Traits are not inherited directly. Rather, genes are inherited and, which can be used to assess the risk of acquiring various along with environmental factors, determine the expression diseases and to tailor their treatment should they arise. The of traits. The genetic information that an individual organism 12 Chapter 1 possesses is its genotype; the trait is its phenotype. For example, Sequence that encodes a trait albinism seen in some Hopis is a phenotype, the information in OCA2 genes that causes albinism is the genotype. DNA Genetic information is carried in DNA and RNA. Genetic information is encoded in the molecular structure Protein of nucleic acids, which come in two types: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nucleic acids are polymers consisting of repeating units called nucleotides; each nucleotide consists of a sugar, a phosphate, and a nitrog- enous base. The nitrogenous bases in DNA are of four types: adenine (A), cytosine (C), guanine (G), and thymine (T). The sequence of these bases encodes genetic information. DNA consists of two complementary nucleotide strands. Most organisms carry their genetic information in DNA, but a few viruses carry it in RNA. The four nitrogenous bases of RNA are adenine, cytosine, guanine, and uracil (U). Chromosome Genes are located on chromosomes. The vehicles of genetic information within a cell are chromosomes (Figure 1.14 Genes are carried on chromosomes. 1.14), which consist of DNA and associated proteins. The cells of each species have a characteristic number of chromo- somes; for example, bacterial cells normally possess a single chromosome; human cells possess 46; pigeon cells possess Mutations are permanent changes in genetic information 80. Each chromosome carries a large number of genes. that can be passed from cell to cell or from parent to offspring. Gene mutations affect the genetic information of only a single Chromosomes separate through the processes of mito- gene; chromosome mutations alter the number or the structure sis and meiosis. The processes of mitosis and meiosis ensure of chromosomes and therefore usually affect many genes. that a complete set of an organism’s chromosomes exists in each cell resulting from cell division. Mitosis is the separation Some traits are affected by multiple factors. Some of chromosomes in the division of somatic (nonsex) cells. traits are affected by multiple genes that interact in complex Meiosis is the pairing and separation of chromosomes in the ways with environmental factors. Human height, for exam- division of sex cells to produce gametes (reproductive cells). ple, is affected by hundreds of genes as well as environmental factors such as nutrition. Genetic information is transferred from DNA to RNA to protein. Many genes encode traits by specifying the struc- Evolution is genetic change. Evolution can be viewed as ture of proteins. Genetic information is first transcribed a two-step process: first, genetic variation arises and, second, from DNA into RNA, and then RNA is translated into the some genetic variants increase in frequency, whereas other amino acid sequence of a protein. variants decrease in frequency. TRY PROBLEM 24 CONCEPTS SUMMARY Genetics is central to the life of every person: it influences a The use of genetics by humans began with the domestication person’s physical features, susceptibility to numerous diseases, of plants and animals. personality, and intelligence. Ancient Greeks developed the concepts of pangenesis and the Genetics plays important roles in agriculture, the inheritance of acquired characteristics. Ancient Romans pharmaceutical industry, and medicine. It is central to the developed practical measures for the breeding of plants and study of biology. animals. All organisms use similar genetic systems. Genetic variation is Preformationism suggested that a person inherits all of his or the foundation of evolution and is critical to understanding her traits from one parent. Blending inheritance proposed all life. that offspring possess a mixture of the parental traits. The study of genetics can be broadly divided into By studying the offspring of crosses between varieties of peas, transmission genetics, molecular genetics, and population Gregor Mendel discovered the principles of heredity. genetics. Developments in cytology in the nineteenth century led to the Model genetic organisms are species about which much understanding that the cell nucleus is the site of heredity. genetic information exists because they have characteristics In 1900, Mendel’s principles of heredity were rediscovered. that make them particularly amenable to genetic analysis. Population genetics was established in the early 1930s,  Introduction to Genetics 13 followed closely by biochemical genetics and bacterial and Genes are located on chromosomes, which are made up of viral genetics. The structure of DNA was discovered in 1953, nucleic acids and proteins and are partitioned into daughter stimulating the rise of molecular genetics. cells through the process of mitosis or meiosis. Cells are of two basic types: prokaryotic and eukaryotic. Genetic information is expressed through the transfer of The genes that determine a trait are termed the genotype; the information from DNA to RNA to proteins. trait that they produce is the phenotype. Evolution requires genetic change in populations. IMPORTANT TERMS genome (p. 4) model genetic organism (p. 5) preformationism (p. 8) transmission genetics (p. 5) pangenesis (p. 8) blending inheritance (p. 9) molecular genetics (p. 5) inheritance of acquired cell theory (p. 9) population genetics (p. 5) characteristics (p. 8) germ-plasm theory (p. 9) ANSWERS TO CONCEPT CHECKS 1. d 3. Developments in cytology in the 1800s led to the 2. No, because horses are expensive to house, feed, and identification of parts of the cell, including the cell nucleus and propagate, they have too few progeny, and their generation time chromosomes. The cell theory focused the attention of biologists is too long. on the cell, eventually leading to the conclusion that the nucleus contains the hereditary information. COMPREHENSION QUESTIONS Answers to questions and problems preceded by an asterisk can 9. What does the concept of the inheritance of acquired be found at the end of the book. characteristics propose and how is it related to the notion of pangenesis? Section 1.1 *10. What is preformationism? What did it have to say about *1. How does the Hopi culture contribute to the high how traits are inherited? incidence of albinism among members of the Hopi tribe? 11. Define blending inheritance and contrast it with 2. Outline some of the ways in which genetics is important to preformationism. each of us. 12. How did developments in botany in the seventeenth and *3. Give at least three examples of the role of genetics in eighteenth centuries contribute to the rise of modern genetics? society today. *13. Who first discovered the basic principles that laid the 4. Briefly explain why genetics is crucial to modern biology. foundation for our modern understanding of heredity? *5. List the three traditional subdisciplines of genetics and 14. List some advances in genetics made in the twentieth summarize what each covers. century. 6. What are some characteristics of model genetic organisms that make them useful for genetic studies? Section 1.3 15. What are the two basic cell types (from a structural Section 1.2 perspective) and how do they differ? 7. When and where did agriculture first arise? What role did *16. Outline the relations between genes, DNA, and genetics play in the development of the first domesticated chromosomes. plants and animals? *8. Outline the notion of pangenesis and explain how it differs from the germ-plasm theory. APPLICATION QUESTIONS AND PROBLEMS Section 1.1 a. Analysis of pedigrees to determine the probability of 17. What is the relation between genetics and someone inheriting a trait evolution? b. Study of people on a small island to determine why a *18. For each of the following genetic topics, indicate whether genetic form of asthma is prevalent on the island it focuses on transmission genetics, molecular genetics, or c. Effect of nonrandom mating on the distribution of population genetics. genotypes among a group of animals 14 Chapter 1 d. Examination of the nucleotide sequences found at the a. Each reproductive cell contains a complete set of genetic ends of chromosomes information. e. Mechanisms that ensure a high degree of accuracy in DNA b. All traits are inherited from one parent. replication c. Genetic information may be altered by the use of a f. Study of how the inheritance of traits encoded by genes on characteristic. sex chromosomes (sex-linked traits) differs from the d. Cells of different tissues contain different genetic inheritance of traits encoded by genes on nonsex information. chromosomes (autosomal traits) 19. Describe some of the ways in which your own genetic *23. Compare and contrast the following ideas about makeup affects you as a person. Be as specific as you can. inheritance. 20. Describe at least one trait that appears to run in your a. Pangenesis and germ-plasm theory family (appears in multiple members of the family). Does b. Preformationism and blending inheritance this trait run in your family because it is an inherited trait c. The inheritance of acquired characteristics and our or because it is caused by environmental factors that are modern theory of heredity common to family members? How might you distinguish between these possibilities? Section 1.3 *24. Compare and contrast the following terms: Section 1.2 a. Eukaryotic and prokaryotic cells *21. Genetics is said to be both a very old science and a very young science. Explain what is meant by this statement. b. Gene and allele 22. Match the description (a through d) with the correct c. Genotype and phenotype theory or concept listed below. d. DNA and RNA Preformationism e. DNA and chromosome Pangenesis Germ-plasm theory Inheritance of acquired characteristics CHALLENGE QUESTIONS Introduction information, you might read one of the articles on ethics 25. The type of albinism that arises with high frequency marked with an asterisk in the Suggested Readings section among Hopi Native Americans (discussed in the for Chapter 1 at www.whfreeman.com/pierce4e. introduction to this chapter) is most likely oculocutaneous a. Should a person’s genetic makeup be used in determining albinism type 2, due to a defect in the OCA2 gene on his or her eligibility for life insurance? chromosome 15. Do some research on the Internet to b. Should biotechnology companies be able to patent newly determine how the phenotype of this type of albinism sequenced genes? differs from phenotypes of other forms of albinism in c. Should gene therapy be used on people? humans and which genes take part. Hint: Visit the Online d. Should genetic testing be made available for inherited Mendelian Inheritance in Man Web site (http://www.ncbi. conditions for which there is no treatment or cure? nlm.nih.gov/omim/) and search the database for albinism. e. Should governments outlaw the cloning of people? Section 1.1 *29. A 45-year old women undergoes genetic testing and 26. We now know as much or more about the genetics of humans discovers that she is at high risk for developing colon as we know about that of any other organism, and humans are cancer and Alzheimer disease. Because her children have the focus of many genetic studies. Should humans be 50% of her genes, they also may have increased risk of considered a model genetic organism? Why or why not? these diseases. Does she have a moral or legal obligation to tell her children and other close relatives about the results Section 1.3 of her genetic testing? *27. Suppose that life exists elsewhere in the universe. All life *30. Suppose that you could undergo genetic testing at age 18 must contain some type of genetic information, but alien for susceptibility to a genetic disease that would not genomes might not consist of nucleic acids and have the appear until middle age and has no available treatment. same features as those found in the genomes of life on a. What would be some of the possible reasons for having such Earth. What might be the common features of all genomes, a genetic test and some of the possible reasons for not having no matter where they exist? the test? 28. Choose one of the ethical or social issues in parts a through b. Would you personally want to be tested? Explain your e and give your opinion on the issue. For background reasoning.