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Produced by the Office of Communications and Public Liaison National Institute of General Medical Sciences National Institutes of Health U.S. Department of Health and Human Services The New Genetics NIH Publication No.10 662 Revised April 2010 http://www.nigms.nih.gov Contents FOREWORD 2 CHAPTER 1: HOW GENES WORK 4 Beautiful DNA 5 Copycat 8 Let’s Call It Even 9 Getting the Message 11 Nature’s CutandPaste Job 14 All Together Now 16 Genetics and You: Nursery Genetics 17 Found in Translation 18 RNA Surprises 19 An Interesting Development 20 The Tools of Genetics: Mighty Microarrays 22 CHAPTER 2: RNA AND DNA REVEALED: NEW ROLES, NEW RULES 24 RNA World 25 Molecular Editor 26 Healthy Interference 29 Dynamic DNA 30 Secret Code 30 Genetics and You: The Genetics of Anticipation 32 Battle of the Sexes 33 Starting at the End 34 The Other Human Genome 36 The Tools of Genetics: Recombinant DNA and Cloning 38 CHAPTER 3: LIFE’S GENETIC TREE 40 Everything Evolves 40 Selective Study 42 Clues from Variation 43 Living Laboratories 46 The Genome Zoo 52 Genes Meet Environment 53 Genetics and You: You’ve Got Rhythm! 56 Animals Helping People 58 My Collaborator Is a Computer 58 The Tools of Genetics: Unlimited DNA 60 CHAPTER 4: GENES ARE US 62 Individualized Prescriptions 64 The Healing Power of DNA 65 Cause and Effect 67 Us vs. Them 68 Genetics and You: Eat Less, Live Longer? 69 Gang Warfare 70 The Tools of Genetics: Mathematics and Medicine 72 CHAPTER 5: 21STCENTURY GENETICS 74 No Lab? No Problem! 76 Hard Questions 78 Good Advice 80 Genetics and You: CrimeFighting DNA 81 Genetics, Business, and the Law 82 Careers in Genetics 85 The Tools of Genetics: Informatics and Databases 86 GLOSSARY 88 Foreword And every living thing Consider just three of Earth’s inhabitants: does one thing the same a bright yellow daffodil that greets the way: To make more of itself, it first copies its spring, the singlecelled creature called molecular instruction manual—its genes—and then passes this infor Thermococcus that lives in boiling hot mation on to its offspring. This cycle has been springs, and you. Even a sciencefiction repeated for three and a half billion years. But how did we and our very distant rela writer inventing a story set on a distant tives come to look so different and develop so many different ways of getting along in the planet could hardly imagine three more dif world? A century ago, researchers began to answer ferent forms of life. Yet you, Thermococcus that question with the help of a science called genetics. Get a refresher course on the basics in and the daffodil are related! Indeed, all of Chapter 1, “How Genes Work.” It’s likely that when you think of heredity the Earth’s billions of living things are kin you think first of DNA, but in the past few years, to each other. researchers have made surprising findings about The New Genetics I Foreword 3 another molecular actor that plays a starring role. Can DNA and RNA help doctors predict Check out the modern view of RNA in Chapter 2, whether we’ll get diseases like cancer, diabetes or “RNA and DNA Revealed: New Roles, New Rules.” asthma? What other mysteries are locked within When genetics first started, scientists didn’t the 6 feet of DNA inside nearly every cell in our have the tools they have today. They could only bodies? Chapter 4, “Genes Are Us,” explains what look at one gene, or a few genes, at a time. Now, researchers know, and what they are still learning, researchers can examine all of the genes in a liv about the role of genes in health and disease. ing organism—its genome—at once. They are Finally, in Chapter 5, “21stCentury doing this for organisms on every branch of the Genetics,” see a preview of things to come. Learn tree of life and finding that the genomes of mice, how medicine and science are changing in big frogs, fish and a slew of other creatures have ways, and how these changes influence society. many genes similar to our own. From metabolism to medicines to agriculture, So why doesn’t your brother look like your the science of genetics affects us every day. It is dog or the fish in your aquarium? It’s because of part of life … part of your life! evolution. In Chapter 3, “Life’s Genetic Tree,” find out how evolution works and how it relates to genetics and medical research. C H A P T E R 1 How Genes Work P eople have known for many years that Proteins do many other things, too. They living things inherit traits from their parents. p rovide the body’s main building materials, That commonsense observation led to agricul f orming the cell’s architecture and structural ture, the purposeful breeding and cultivation of components. But one thing proteins can’t do is animals and plants for desirable characteristics. make copies of themselves. When a cell needs Firming up the details took quite some time, more proteins, it uses the manufacturing instruc though. Researchers did not understand exactly tions coded in DNA. how traits were passed to the next generation The DNA code of a gene—the sequence of until the middle of the 20th century. its individual DNA building blocks, labeled A Now it is clear that genes are what carry our (adenine), T (thymine), C (cytosine) and G traits through generations and that genes are ( guanine) and collectively called nucleotides— made of deoxyribonucleic acid (DNA). But spells out the exact order of a protein’s building genes themselves don’t do the actual work. blocks, amino acids. Rather, they serve as instruction books for mak Occasionally, there is a kind of typographical ing functional molecules such as ribonucleic error in a gene’s DNA sequence. This mistake— acid (RNA) and proteins, which perform the which can be a change, gap or duplication—is chemical reactions in our bodies. called a mutation. Genetics in the Garden In 1900, three European scientists inde The monk Gregor Mendel first described pendently discovered an obscure research how traits are inherited paper that had been published nearly 35 from one generation to years before. Written by Gregor Mendel, the next. an Austrian monk who was also a scien tist, the report described a series of offspring and learned that these characteristics breeding experiments performed with pea were passed on to the next generation in orderly, plants growing in his abbey garden. predictable ratios. Mendel had studied how pea plants When he crossbred purpleflowered pea plants inherited the two variant forms of easytosee with whiteflowered ones, the next generation had traits. These included flower color (white or purple) only purple flowers. But directions for making white and the texture of the peas (smooth or wrinkled). flowers were hidden somewhere in the peas of that Mendel counted many generations of pea plant generation, because when those purpleflowered The New Genetics I How Genes Work 5 A mutation can cause a gene to encode a Beautiful DNA protein that works incorrectly or that doesn’t Up until the 1950s, scientists knew a good deal work at all. Sometimes, the error means that no about heredity, but they didn’t have a clue what protein is made. DNA looked like. In order to learn more about But not all DNA changes are harmful. Some DNA and its structure, some scientists experi mutations have no effect, and others produce mented with using X rays as a form of molecular new versions of proteins that may give a survival photography. advantage to the organisms that have them. Over Rosalind Franklin, a physical chemist work time, mutations supply the raw material from ing with Maurice Wilkins at King’s College in which new life forms evolve (see Chapter 3, London, was among the first to use this method “Life’s Genetic Tree”). to analyze genetic material. Her experiments plants were bred to each other, some of their off factors, whatever they were, must be physical spring had white flowers. What’s more, the material because they passed from parent to secondgeneration plants displayed the colors in a offspring in a mathematically orderly way. It wasn’t predictable pattern. On average, 75 percent of the until many years later, when the other scientists secondgeneration plants had purple flowers and unearthed Mendel’s report, that the factors were 25 percent of the plants had white flowers. Those named genes. same ratios persisted, and were reproduced when Early geneticists quickly discovered that the experiment was repeated many times over. Mendel’s mathematical rules of inheritance applied Trying to solve the mystery of the missing color not just to peas, but also to all plants, animals and blooms, Mendel imagined that the reproductive people. The discovery of a quantitative rule for cells of his pea plants might contain discrete inheritance was momentous. It revealed that a “factors,” each of which specified a particular trait, common, general principle governed the growth such as white flowers. Mendel reasoned that the and development of all life on Earth. 6 National Institute of General Medical Sciences produced what were referred to at the time as “the most beautiful Xray photographs of any CO subsOtathnecre secvieern ttaisktes,n i.”n cluding zoologist James LDSPRINGHARBO Watson and physicist Francis Crick, both work RLABO RATO Kinign gadt oCmam, wberirde gter yUinngiv teor sditeyt eirnm thinee U thneit sehda pe RYARCHIVES . In 1953, Watson and Crick created their historic of DNA too. Ultimately, this line of research model of the shape of DNA: the double helix. revealed one of the most profound scientific discoveries of the 20th century: that DNA exists handrails—were complementary to each other, as a double helix. and this unlocked the secret of how genetic The 1962 Nobel Prize in physiology or medi information is stored, transferred and copied. cine was awarded to Watson, Crick and Wilkins In genetics, complementary means that if for this work. Although Franklin did not earn a you know the sequence of nucleotide building share of the prize due to her untimely death at age blocks on one strand, you know the sequence of 38, she is widely recognized as having played a nucleotide building blocks on the other strand: significant role in the discovery. A always matches up with T and C always links The spiral staircaseshaped double to G (see drawing, page 7). helix has attained global status as Long strings of nucleotides form genes, the symbol for DNA. But what and groups of genes are packaged tightly into is so beautiful about the structures called chromosomes. Every cell in your discovery of the twisting body except for eggs, sperm and red blood cells ladder structure isn’t just contains a full set of chromosomes in its nucleus. its good looks. Rather, the If the chromosomes in one of your cells were structure of DNA taught uncoiled and placed end to end, the DNA would researchers a fundamental be about 6 feet long. If all the DNA in your body lesson about genetics. It taught were connected in this way, it would stretch them that the two connected approximately 67 billion miles! That’s nearly strands—winding together like parallel 150,000 round trips to the Moon. . Rosalind Franklin’s original Xray diffraction photo revealed the physical structure of DNA. OREGON STATE UNIVERSITY LIBRARIES SPECIAL COLLECTIONS
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