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The New GeneticsNIH Publication No.10 662Revised April 2010http://www.nigms.nih.gov
ContentsF O RE W O RD2C H A P TE R 1: H O W G E N E S W O RK4Beautiful DNA5Copycat8Let’s Call It Even9Getting the Message11Nature’s Cut and Paste Job14All Together Now16Genetics and You: Nursery Genetics17Found in Translation18RNA Surprises19An Interesting Development20The Tools of Genetics: Mighty Microarrays22C H A P TE R 2: RN A A N D D N A RE VE A LE D : N E W RO LE S , N E W RU LE S24RNA World25Molecular Editor26Healthy Interference29Dynamic DNA30Secret Code30Genetics and You: The Genetics of Anticipation32Battle of the Sexes33Starting at the End34The Other Human Genome36The Tools of Genetics: Recombinant DNA and Cloning38C H A P TE R 3: LI F E ’ S G E N E TI C TRE E40Everything Evolves40Selective Study42Clues from Variation43Living Laboratories46
The Genome Zoo52Genes Meet Environment53Genetics and You: You’ve Got Rhythm!56Animals Helping People58My Collaborator Is a Computer58The Tools of Genetics: Unlimited DNA60C H A P TE R 4: G E N E S A RE U S62Individualized Prescriptions64The Healing Power of DNA65Cause and Effect67Us vs. Them68Genetics and You: Eat Less, Live Longer?69Gang Warfare70The Tools of Genetics: Mathematics and Medicine72C H A P TE R 5: 2 1 S T C E N TU RY G E N E TI C S74No Lab? No Problem!76Hard Questions78Good Advice80Genetics and You: Crime Fighting DNA81Genetics, Business, and the Law82Careers in Genetics85The Tools of Genetics: Informatics and Databases86G LO S SA RY88
ForewordConsider just three of Earth’s inhabitants:And every living thingdoes one thing the samea bright yellow daffodil that greets theway: To make more ofitself, it first copies itsspring, the single celled creature calledThermococcus that lives in boiling hotmolecular instructionmanual—its genes—and then passes this infor mation on to its offspring. This cycle has beensprings, and you. Even a science fictionrepeated for three and a half billion years.But how did we and our very distant rela writer inventing a story set on a distantplanet could hardly imagine three more dif tives come to look so different and develop somany different ways of getting along in theworld? A century ago, researchers began to answerferent forms of life. Yet you, Thermococcusthat question with the help of a science calledgenetics. Get a refresher course on the basics inand the daffodil are related! Indeed, all ofthe Earth’s billions of living things are kinChapter 1, “How Genes Work.”It’s likely that when you think of heredityyou think first of DNA, but in the past few years,to each other.researchers have made surprising findings about
The New Genetics I Foreword 3another molecular actor that plays a starring role.Can DNA and RNA help doctors predictCheck 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 withinWhen genetics first started, scientists didn’tthe 6 feet of DNA inside nearly every cell in ourhave the tools they have today. They could onlybodies? Chapter 4, “Genes Are Us,” explains whatlook 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 areFinally, in Chapter 5, “21st Centurydoing this for organisms on every branch of theGenetics,” see a preview of things to come. Learntree of life and finding that the genomes of mice,how medicine and science are changing in bigfrogs, fish and a slew of other creatures haveways, and how these changes influence society.many genes similar to our own.So why doesn’t your brother look like yourdog or the fish in your aquarium? It’s because ofevolution. In Chapter 3, “Life’s Genetic Tree,”find out how evolution works and how it relatesto genetics and medical research.From metabolism to medicines to agriculture,the science of genetics affects us every day. It ispart of life part of your life!
CHAPTER 1How Genes WorkPeople have known for many years thatliving things inherit traits from their parents.Proteins do many other things, too. Theyprovide the body’s main building materials,That common sense observation led to agricul forming the cell’s architecture and structuralture, the purposeful breeding and cultivation ofcomponents. But one thing proteins can’t do isanimals and plants for desirable characteristics.make copies of themselves. When a cell needsFirming up the details took quite some time,more proteins, it uses the manufacturing instruc though. Researchers did not understand exactlytions coded in DNA.how traits were passed to the next generationuntil the middle of the 20th century.Now it is clear that genes are what carry ourThe DNA code of a gene—the sequence ofits individual DNA building blocks, labeled A(adenine), T (thymine), C (cytosine) and Gtraits through generations and that genes are(guanine) and collectively called nucleotides—made of deoxyribonucleic acid (DNA). Butspells out the exact order of a protein’s buildinggenes themselves don’t do the actual work.blocks, amino acids.Rather, they serve as instruction books for mak Occasionally, there is a kind of typographicaling functional molecules such as ribonucleicerror in a gene’s DNA sequence. This mistake—acid (RNA) and proteins, which perform thewhich can be a change, gap or duplication—ischemical reactions in our bodies.called a mutation.Genetics in the GardenIn 1900, three European scientists inde pendently discovered an obscure researchpaper that had been published nearly 35years before. Written by Gregor Mendel,an Austrian monk who was also a scien tist, the report described a series ofbreeding experiments performed with peaplants growing in his abbey garden.Mendel had studied how pea plantsinherited the two variant forms of easy to seetraits. These included flower color (white or purple)and the texture of the peas (smooth or wrinkled).Mendel counted many generations of pea plantThe monk GregorMendel first describedhow traits are inheritedfrom one generation tothe next.offspring and learned that these characteristicswere passed on to the next generation in orderly,predictable ratios.When he cross bred purple flowered pea plantswith white flowered ones, the next generation hadonly purple flowers. But directions for making whiteflowers were hidden somewhere in the peas of thatgeneration, because when those purple flowered
The New Genetics I How Genes Work 5A mutation can cause a gene to encode aBeautiful DNAprotein that works incorrectly or that doesn’tUp until the 1950s, scientists knew a good dealwork at all. Sometimes, the error means that noabout heredity, but they didn’t have a clue whatprotein is made.DNA looked like. In order to learn more aboutBut not all DNA changes are harmful. SomeDNA and its structure, some scientists experi mutations have no effect, and others producemented with using X rays as a form of molecularnew versions of proteins that may give a survivalphotography.advantage to the organisms that have them. OverRosalind Franklin, a physical chemist work time, mutations supply the raw material froming with Maurice Wilkins at King’s College inwhich 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 experimentsplants were bred to each other, some of their off spring had white flowers. What’s more, thesecond generation plants displayed the colors in apredictable pattern. On average, 75 percent of thesecond generation plants had purple flowers and25 percent of the plants had white flowers. Thosesame ratios persisted, and were reproduced whenthe experiment was repeated many times over.Trying to solve the mystery of the missing colorblooms, Mendel imagined that the reproductivecells of his pea plants might contain discrete“factors,” each of which specified a particular trait,such as white flowers. Mendel reasoned that thefactors, whatever they were, must be physicalmaterial because they passed from parent tooffspring in a mathematically orderly way. It wasn’tuntil many years later, when the other scientistsunearthed Mendel’s report, that the factors werenamed genes.Early geneticists quickly discovered thatMendel’s mathematical rules of inheritance appliednot just to peas, but also to all plants, animals andpeople. The discovery of a quantitative rule forinheritance was momentous. It revealed that acommon, general principle governed the growthand development of all life on Earth.
6National Institute of General Medical Sciencesproduced what were referred to at the time asCOLD SPRING HARBOR LABORATORY ARCHIVES“the most beautiful X ray photographs of anysubstance ever taken.”Other scientists, including zoologist JamesWatson and physicist Francis Crick, both work ing at Cambridge University in the UnitedKingdom, were trying to determine the shapeof DNA too. Ultimately, this line of research. In 1953, Watson and Crick created their historicmodel of the shape of DNA: the double helix.revealed one of the most profound scientificdiscoveries of the 20th century: that DNA existshandrails—were complementary to each other,as a double helix.and this unlocked the secret of how geneticThe 1962 Nobel Prize in physiology or medi cine was awarded to Watson, Crick and WilkinsIn genetics, complementary means that iffor this work. Although Franklin did not earn ayou know the sequence of nucleotide buildingshare of the prize due to her untimely death at ageblocks on one strand, you know the sequence of38, she is widely recognized as having played anucleotide building blocks on the other strand:significant role in the discovery.The spiral staircase shaped doublehelix has attained global status asthe symbol for DNA. But whatis so beautiful about theand groups of genes are packaged tightly intostructures called chromosomes. Every cell in yourcontains a full set of chromosomes in its nucleus.If the chromosomes in one of your cells werestructure of DNA taughtuncoiled and placed end to end, the DNA wouldresearchers a fundamentalbe about 6 feet long. If all the DNA in your bodystrands—winding together like parallelOREGON STATE UNIVERSITY LIBRARIESLong strings of nucleotides form genes,ladder structure isn’t justthem that the two connectedoriginal X ray diffractionphoto revealed the physicalstructure of DNA.to G (see drawing, page 7).body except for eggs, sperm and red blood cellslesson about genetics. It taught. Rosalind Franklin’sA always matches up with T and C always linksdiscovery of the twistingits good looks. Rather, theSPECIAL COLLECTIONSinformation is stored, transferred and copied.were connected in this way, it would stretchapproximately 67 billion miles! That’s nearly150,000 round trips to the Moon.
The New Genetics I How Genes Work 7DNA Structure The long, stringy DNA that makes up genes isspooled within chromosomes inside the nucleusof a cell. (Note that a gene would actually be a muchlonger stretch of DNA than what is shown TCGThymineTGeneGCTDNA consists of two long, twisted chains made upof nucleotides. Each nucleotide contains one base,one phosphate molecule and the sugar moleculedeoxyribose. The bases in DNA nucleotides areadenine, thymine, cytosine and guanine.PNucleotideSCTCGAAdenineAASugar phosphatebackboneBasesGADNAC
8National Institute of General Medical SciencesCopycatIt’s astounding to think thatyour body consists of trillionsof cells. But what’s mostamazing is that it all startswith one cell. How does thismassive expansion take place?As an embryo progressesthrough development, its cells. Humans have 23 pairs of chromosomes. Male DNA (pictured here)contains an X and a Y chromosome, whereas female DNA containstwo X chromosomes.must reproduce. But beforea cell divides into two new,CYTOGENETICS LABORATORY, BRIGHAM AND WOMEN’S HOSPITALnearly identical cells, it mustcopy its DNA so there will be a complete set ofthe complementary new strand. The process,genes to pass on to each of the new cells.called replication, is astonishingly fast andTo make a copy of itself, the twisted, com accurate, although occasional mistakes, such aspacted double helix of DNA has to unwind anddeletions or duplications, occur. Fortunately, aseparate its two strands. Each strand becomescellular spell checker catches and corrects nearlya pattern, or template, for making a new strand,all of these errors.so the two new DNA molecules have one newstrand and one old strand.The copy is courtesy of a cellular proteinMistakes that are not corrected can lead todiseases such as cancer and certain genetic disor ders. Some of these include Fanconi anemia, earlymachine called DNA polymerase, which readsaging diseases and other conditions in whichthe template DNA strand and stitches togetherpeople are extremely sensitive to sunlight andsome chemicals.DNA copying is not the only time when DNAdamage can happen. Prolonged, unprotected sunexposure can cause DNA changes that lead toskin cancer, and toxins in cigarette smoke cancause lung cancer. When DNA polymerase makes an error while copying a gene’sDNA sequence, the mistake is called a mutation. In this example,the nucleotide G has been changed to an A.
The New Genetics I How Genes Work 9C GATCIt may seem ironic, then, that many drugsGAused to treat cancer work by attacking DNA. That’sTTAbecause these chemotherapy drugs disrupt theDNA copying process, which goes on much fasterCGTin rapidly dividing cancer cells than in otherAGcells of the body. The trouble is that most of theseCTdrugs do affect normal cells that grow andATdivide frequently, such as cells of the immunesystem and hair cells.AUnderstanding DNA replication better couldAAGTTbe a key to limiting a drug’s action to cancerAGcells only.CAGTGCAT TCGLet’s Call It EvenAfter copying its DNA, a cell’s next challenge isCNew strandGgetting just the right amount of genetic materialinto each of its two offspring.CCAGMost of your cells are called diploidGTACA(“di” means two, and “ploid” refers to sets ofCTGTCATchromosomes) because they have two sets ofchromosomes (23 pairs). Eggs and sperm areAdifferent; these are known as haploid cells. EachGso that at fertilization the math will work out:AACChaploid cell has only one set of 23 chromosomesTGGCTACGTA haploid egg cell will combine with a haploidsperm cell to form a diploid cell with the rightAnumber of chromosomes: 46.TAChromosomes are numbered 1 to 22,according to size, with 1 being the largestchromosome. The 23rd pair, known as the sexchromosomes, are called X and Y. In humans,abnormalities of chromosome number usuallyoccur during meiosis, the time when a cell. During DNA replication, each strand of theoriginal molecule acts as a template forthe synthesis of a new, complementaryDNA strand.TT
10National Institute of General Medical SciencesMeiosisChromosomesfrom parents During meiosis, chromosomesfrom both parents are copiedand paired to exchange portionsof DNA.Cell nucleusChromosomesreplicateMatchingchromosomespair up This creates a mix of new geneticmaterial in the offspring’s cells.Nucleus divides intodaughter nucleiDaughter nucleidivide againChromosomes swapsections of DNAChromosome pairs divideChromosomes divide;daughter nuclei havesingle chromosomesand a new mix ofgenetic material
The New Genetics I How Genes Work 11reduces its chromosomes from diploid to haploidin creating eggs or sperm.What happens if an egg or a sperm cell
Genetics and You: The Genetics of Anticipation 32 Battleof the Sexes 33 Startingat the End 34 TheOther Human Genome 36. The Tools of Genetics: Recombinant DNA and Cloning 38. CHAPTER 3: LIFE’S GENETIC TREE. 40 EverythingEvolves 40 Selecti
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