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MOLECULAR BIOLOGY GENE OF THE S E V E N T H E D I T I O N This page . The paper by Watson and Crick proposing the double helix ended with a now. Library of Congress Cataloging-in-Publication Data Watson, James D. Molecular biology of the gene / James D. Watson, Cold Spring Harbor Laboratory, Tania. Molecular Biology of the Gene. F T H. E D I T I O N. James D. Watson. Cold Spring Harbor. Laboratory. Tania A. Baker. Massachusetts Institute of Technology .
Watson, a businessman descended mostly from colonial English immigrants to America. He was part of a distributed group of researchers who were making use of the viruses that infect bacteria , called bacteriophages. Importantly, the members of the Phage Group sensed that they were on the path to discovering the physical nature of the gene. In , Watson took a course with Felix Haurowitz that included the conventional view of that time: that genes were proteins and able to replicate themselves. Watson's research project involved using X-rays to inactivate bacterial viruses. Watson wanted to explore the structure of DNA, and his interests did not coincide with Kalckar's. After obtaining some results from his phage and other experimental research  conducted at Indiana University, Statens Serum Institut Denmark , CSHL, and the California Institute of Technology , Watson now had the desire to learn to perform X-ray diffraction experiments so he could work to determine the structure of DNA.
Watson, a businessman descended mostly from colonial English immigrants to America. He was part of a distributed group of researchers who were making use of the viruses that infect bacteria , called bacteriophages.
Importantly, the members of the Phage Group sensed that they were on the path to discovering the physical nature of the gene. In , Watson took a course with Felix Haurowitz that included the conventional view of that time: that genes were proteins and able to replicate themselves. Watson's research project involved using X-rays to inactivate bacterial viruses. Watson wanted to explore the structure of DNA, and his interests did not coincide with Kalckar's.
After obtaining some results from his phage and other experimental research  conducted at Indiana University, Statens Serum Institut Denmark , CSHL, and the California Institute of Technology , Watson now had the desire to learn to perform X-ray diffraction experiments so he could work to determine the structure of DNA. That summer, Luria met John Kendrew ,  and he arranged for a new postdoctoral research project for Watson in England.
Nearer Secret of Life. Oughton were some of the first people in April to see the model of the structure of DNA , constructed by Crick and Watson; at the time, they were working at Oxford University 's Chemistry Department.
According to the late Beryl Oughton, later Rimmer, they all travelled together in two cars once Dorothy Hodgkin announced to them that they were off to Cambridge to see the model of the structure of DNA.
Watson subsequently presented a paper on the double-helical structure of DNA at the 18th Cold Spring Harbor Symposium on Viruses in early June , six weeks after the publication of the Watson and Crick paper in Nature.
Many at the meeting had not yet heard of the discovery. Watson, Crick, and Wilkins were awarded the Nobel Prize in Physiology or Medicine in for their research on the structure of nucleic acids. They used some of her unpublished data—without her consent—in their construction of the double helix model of DNA. Franklin told Crick and Watson that the backbones had to be on the outside; before then, Linus Pauling and Watson and Crick had erroneous models with the chains inside and the bases pointing outwards.
The X-ray diffraction images collected by Gosling and Franklin provided the best evidence for the helical nature of DNA. Watson and Crick had three sources for Franklin's unpublished data: Her seminar, attended by Watson,  Discussions with Wilkins,  who worked in the same laboratory with Franklin, A research progress report that was intended to promote coordination of Medical Research Council -supported laboratories.
According to one critic, Watson's portrayal of Franklin in The Double Helix was negative and gave the appearance that she was Wilkins' assistant and was unable to interpret her own DNA data. Franklin consulted with Watson on her tobacco mosaic virus RNA research. Franklin's letters begin on friendly terms with "Dear Jim", and conclude with equally benevolent and respectful sentiments such as "Best Wishes, Yours, Rosalind".
Each of the scientists published their own unique contributions to the discovery of the structure of DNA in separate articles, and all of the contributors published their findings in the same volume of Nature. These classic molecular biology papers are identified as: Watson J. His work at Harvard focused on RNA and its role in the transfer of genetic information.
Watson continued to be a member of the Harvard faculty until , even though he took over the directorship of Cold Spring Harbor Laboratory in This mechanism is caBed crossing over. Al the start of meiosis. Al this slage. Janssens postulaled thal. These events could create fOUT broken ends. In lhis manner, recombinant eh ro- matids mighl be produced Ibat conlain a segment derived rrom each of the original homologous chromosomes.
Formal proof of Janssens's bypolhesis that chromosomes physicaUy interchange material during synapsis carne more Iban 20 years later, when in , Barbara McClintock and Harriel B. In most organisms. Qccas,ionally, however. McClintod and Creighton found one such palr used iI to show mal oosslllg over InvoIves actual physical exchanges between me pilired chromosomes.
W1len sudl c. The colored box in the rlgUre idenllfies me chromosomes of me e, wx oflspring. They reasoned that genes located close together on a chromosome would assorl with one another much moro regular!
They immediately saw this as a way to locate map the relative positions of gene: Consider the segregati on of three genes all located on the same chromosome. The arrangement of tbe genes can be deter- mincd by means of tbree crosscs.
A cross between AC and oc simi- larly give: Each ccoss will produce a spe- cme ratio of parental lo recombinanl progeny. Consider, for example, the ract Ihat lhe fi. The gene arrangement thal best fit s these data is o-c-b Figure The correctness of gene order suggested by crosses of two gene factors cao lIsually be unambiguously confirmed by three-factor crosses.
When the tbree genes used in Ihe preceding example are foI- lowed in the c. They fall inlo tmee groups of reciproca I paies. By looking for the Ieast frequent class. The res ults in Figure irome- diately confirm the order hinted at by the two-factor crosses.
Only if the order is a-c-b does the fact that the rare recombinants are AcB and aCb make sense. The existence oC multiple crossovers means tbat the amount of recombination between the outside marke. This probability subtracted from the suro oC the frequencies expresses more accurately tbe amounl of reeombination. The simple. Us ing sud reasoni ng. Mosl importantl y. The genetic map of one of the chromosomes of Drosophila is showll in Figure l -B. Dislances Letween genes on such 8 map are measured in map units, which are related lo Ihe frequency of recombination between Ihe genes.
Bccaul e of the high probability ol" double crossovers belween widely spaced genes, such assignmenls of map unit s can he considered aflcurate only if recombinatioll bctween closely spnced genes is foUowed. Even when two genes are al tho rae ends of a very long chromosome.
Only after large numbers of genes had becn mapped was it possible to dcmonstrate convincingly that Ihe Ilumber 01" linkage groups equalled the numbcr of cytologically visible chromosomes. In , Morgan. Sturtevant , Hermann J. We now rank this concepl. The Ie.
VVhen finite numbers 01 progeny ale reaxded, the exact va! Wil]g Plexus Venahon Co"",," Thoral mal! Sonce fOUf chromosomeswere cytolog,cally observed.
Notice thal mutalions in various genes can acl lo aller a SIngle characlElf. Genes are normaUy copied exactl y duriog chro- mosome dllplication. Thi s process is necessari ly raro; otherwise. There is, instead, a strong advantage in there being a small bul finite mutation rate; it provides a constant source of new variabil il y. Iike wings or eyes. Ihese biologists believed that Iberc musl also occur more powerfuJ "macromutations.
Ronald A. F'isher, and John Burclen Sanderson Haldane. They showed that , considering Ihe great age of Earth. By the s. In the aU lour ""lfote major works.
No real progress could be made. Even the realization thal both nucleic acirls and proleins are presenl in chromosomes did no! The most fruitful spoculations focused atlention on the fllel lhat genes must be. This fad immediately raised tite profound chemical question of how a complicated mol: Sorne physicists also became intrigued wil b the gene. Such Ihoughts, however, never realIy took root.
MuHer and L. Stadler's independenl discoverir. But even here, so man ' special assumptions were required that virtually no one. Al first these studies were difficult, sinee no one Imew anything aboul Ihe proteins thal were prcscnt in structures such as the eye or the wing.
Qne of Lhe first useful examples carne from a study of a hereditary diseasc affecting amino acid metabolismo Sponta- neous mutations occur in humans affecting lhe abitity lo metabolize the amino acid phenylalanine.
When individuals homozygous for lhe mutan! Irait eal food containing phenylalanine. Sueh diseases. Carrod, as early as ,! Carrad's general hypothesis of a gene-enzyme relationship was extended in the s by work on fl ower pigments by Haldane and Rose Scotl-Moncrieff in England, studies on Ihe ha ir pigmenl of Ihe guinea pi. Deadle, working first in France and then in California. In alt cases. As early as They were aware, moreover, Ihat contemporary knowledgc of nucleic acid and protein chemistry was completely inadequale for a fundamental chemical att ack uven the most suitable biological systems.
Hcreditary factors were first dis- covered and described by Mendel in Each gene can exist in a variety of differcnt fonllS called allcles.
Mendet proposed Ihal a hercditary faclor now knowll to be a gene for each hercditary lraH is given by each parent lo each of its offspring. Tbe pliysical basis for Ihis behavior is Ihc distri bution of homologous chromosomcs durillg meiosis: Cenes affccting di ffercnl characlcrislics are sometimes inhcrited independelll ly of each olher. Lecause they are located on differenl chromosomes.
In any case. Crossi ll g nver transfers genes initiaJly Jocated on a paternally de- rived chromosome onlo gene groups originati ng rroro the maternal paren!. Oifferenl aUcl es from Ihe same gene arise by inheritabJe changes mutations in the gene itself.
Nonnally, genes are extremely stable and are copied m.: Murallon cines, however. As soon as large numbers of spontaneous muta- tions had been described, it became obvious that a one gene- Dile characterislic relationship dnes nol exist and thal all complex characteristics are under Ihe control of many genes.
Tho mosl sensible idel!. Modern genelics. Benjamin Cummings. Menlo Park, California. Beadle G. W, and Ephrussi B. Development of eye color i n Drosophila: Diffusible substa noes and their ill lerrelati olLs.
Cenetics Carlson E,J. Phi ladelphia. The Ufe arrd work al H. Caspari E. Cytoplasmic inheritance. Genetics 2: Correns C. Njcltt Mcndel"de vel'cl'bung OO. Dobzhansky T. Ccnetics Dod the origio of spccies, 2nd edition. Columbia Universily Press, New York. Fisher R. Clflrendon Press, Uxford, England.
Garrod A. Lancet 2: Ha ldane J. TIte COIlr. Huxley J. The modem sYJl thesis. New York. Lea O. Adiolts of rodiatioll s on li ving cells. Macmill an. Nc", York. Mayr E. Systematics and tlm origin o[ species. Cambridge, Mossachuselts. McClirtlock B. Chromosome organization 8nd gene expression.
Cold Spriug Harbar Symp. Science McClintock B. A correlation of cytological and genetical crossi ng over in Zeo Muys. Moore ,. Heredity und development. Heodings in hereditf alld development. Ox ord University Prcss, Oxford.
MOIllan T. Morgan T. TIte mechanism of Mettdeliall heredity. Muller H. Arlificial lransmutation oC the gene. Olby R. Grigins o[ Mendelism.
Constable and Company LId. Petars J. CJassic papen; in genetics. Prenlice- Ha ll. RhOftdcs M. Plastid mutati ons. Cold Sprlng Har- bar Symp. Soger R. Cytaplasmic genes and organelJes. Academic Press , Now York. A biochcmical survey of sorne Mcndeli fln fat. Genetics Simpson C. Columbia Uni vcrsit y PresS. Sonncborn T. The cytoplasm i n heredity.
Heredity 4: Mutations in barley induced by X-rays and rndiulII. Sciellce St urlevanl A. The li near arrangement of six sex- li nked factors in Drosophila as shown by mode of assuciat ioll. Sturtevant A. Oover, Naw Ymk. Sutt OI1 W. Wilson E. Mocmi ll rlll, Ncw York. Wright S. Evolution in Mendclian populations. Geoetics The physiology uf Ul e gene. Re", It was generaJl y assumed tha!
Ihey appeared lo be tbe onJy biomolccules with sufficienl complexity. In lhe early s. Beadle and Edward Tat um, "",as generating incrensingly slraog evidence supporting Ihe year-old hypothesis of Archibald E. Currad Ihat genes work by con- IroUing tbe synthesis of specific enzymes the one gene-one enzyme bypolhesis.
Ihe key problcm was Ihe way genes partie- ipate in the synthesis of proteins. Ihe simples! In altempling lo test this proposal. Such schemes would require. This situation c1eurly poses a paradox. With such an assumption. It did nol seem Iikely. In fact, all lhe currenl knowledge poinled lO the opposite conclusion of one protein, one function. In Englisb microbiologist frederick Griffith made the startling observation tha! This raised the possibility that when pathogenic ccHs are killed by heat, their genetic components remain undamagcd.
Subsequent research has confirmed this genetic interpretation. When the S smooth allele of the capsule gene is present, Ihen a capsule is fonned around the cell tbat is nccessary foc pathogenesis the formati on of fl cnpsule also gives a smooth appearancc to the colonies fOffiled from these cells. When the R lrough allele oC Ihi s gene is presenl, no capsule is formed and the respective eeUs are no!
Al that time, the vast majority of biochemisls sti ll beHeved that genes were proteins. Avery and his colleagues al tbc RockefeUcr lnstitute nonpall1ogemc R rough cell entryofdlromosome fragmenl bearing caps inlo capR cell recombmalJon and cel! MacLeod and Madyn McCarly. The addition oC either pancreatic ribonu- cIease which degrade! RNA or various proleolytic enzymes protein- destTOying had no influence on the transforming actjvity.
By it was possible to oblain a number of essentially pure viruses and to determi ne which types oC molecules were present in them. This work led lo the very importanl generalization Ihat aH vi ruses contain nucleic ncid. Since there was at that time a growing reaJization that viruses contain genetic material, the question immediately arose as lO whelher the nucJeic acid componen was the carrier of viral genes.
A crucial tesl of Ihe question carne from isotopie study of Ihe multi plication ot' T2. In Ihese experiments, performed in by Alfred D. Moreover, il was possible to show Ihat Httl e or the parental protein even enters the bacteria; inslead, il stays attached to the outside of Ihe bacteria cell.
This point was neally sbown by violently agi tati ng infected bacteria after the entrance 01' the ONA; the prolcin coats were shaken off wilhout nITecting the abilily of the bacteria to Conn oew phage parlicles. With sorne viruses it is now possible lo do an evell more convincing experiment. Thll primary function of viral protein is Ihus lo protect its genetic nucJeic acid com- ponent in its movement from one cell lo another.
Thus no reason exists for proteins to pl ay any part in the struelure of a gene. It was nol unlillhe early s thal high-quality The Double I-lelix 21 pathogenic S smoolh rol! Adapted from Slah! Copyright 0 Rcpnnled by permis5Ioo of Pearson Educallon, tne.
These photographs suggesled nol only Ihal Ibe underlying ONA strucl ure was helical bul Ihat it was com- posed of more than olle polYllucJeotide chain-either two or lhree.
Al the same time. In a group of OI-ganic chemisls working in the laboratory of Alexander Todd showed thal 3' - 5' phosphodiester bonds regularly l. Crick, and Vladimir Vand. This theory made it easy 10 test possible DNA slructures on a Irial-and-error basis. The correct solution. Watson, then working in lhe laboratory of Max Perulz and 10hn Kendrew. Their Brri val al lhe correct answer depended largely on finding Ihe stereochemically mosl favorable configuration compat ible with lhe X-cay diffract.
In tbe double helix, the two DNA chains are held together by hydrogen bonds a noncovalent chemical bond; see Olaptcr 3 between pairs of bases on lhe opposing strands Figure This base pairing is very specific: The purine adonine only base-pairs lo lhe pyrimidine thymine, while the purine guanine only base-pairs to tbe pyrimidine cytosine, In double-helical DNA, the number of A residues must be equal to the number of T residues.
Iikowise be equal see Box , Chnrgafrs Rules. As a resul t, Ule sl;. Tbe discovery of Ihe double helix initialed a profound revolution in lhe way many geneticists analyzed Iheir data. The gene was no longer a rnysterious entity.
Mosl of the excitemenl, however, carno not meroly from the fact that the structurc was solved, but also from Ihe nature of the structuro. Before the answer was known, there had always been the worry tha! Fortunalely, however, lhe was irnmensely cxciting. This photograph. The vey heavy blad regions al the top dOO bottom tell!
Noture Phosphale groups ronnect Ihe 3' c. Thesc fincli ngs q: Chargaff's experiments also shoNed mal the relative ratios of the fout bases were not random.
In oddition, fl. Never, until senous attention v. Afie' Chargafl E. These came much faster than anticipated by molecular geneticists. Over Ihe next several years. Komberg wenl on lo show that a specific polymeri zing enzyme was needed lo catalyze the linking together oC the building-bl ock precursors of DNA. Further studies identified a single polypeptide.
It li nks tha nucleotide precursors by 3' - 5' phos- phodiester bonds Figure 2 M B. Thi s was first demonslrated by allowing the ellzyme lO work in the presence of DNA molecules that contained varying amounts oC A: T and G: C base pairs. During tbis cell-free synthesis. The structUI'e'i 01 Ihe different componenlS 01 each of lile loul nudeotides are Their success was due in part to the use of the heavy isotope 15N as a tag to differentially label the parental and daughter ONA strands.
Also conlIibuting to the success of Ihe experiment was the development of procedures for separating heavy from light ONA in density gradients of heavy salts Iike cesium chlo- ride. Whcn the correct initiaJ solution density is choscn, the individual ONA molecoles will move to the central region of the centrifuge tube where their density equals that oC the salt solution. Jn this situation. IC bacteria containing heavy ONA are trans- ferred to a light medium containing 14N and allowed to grow.
Afi er ona generation ol' growth, all the DNA molecules shou1d contain one heavy strand and one light strand and thus be oC intermediate hybrid density. This result is exactl y what Meselson and Stahl observed. These experiments ruled out Iwo ot hcr models al the time: In Ihis model. In the dispersive model. The e;. Even before strnnd separation during DNA replication was experimentally verified, the main concem of molecular genet icists had turned to how the genetic inforrnation of DNA functions to order amino acids during protein syn- thesis sea Box , Evidence thal Genes Control Amina Acid Sequences in Proteins.
With all DNA chains capable of forming double halices, the essence of t. Thus, as information-containing entities. G, e, and T. Even with only four letters, the number of potential DNA sequences 4 N , where N is the number of letlers in the sequence is very, very large for even the smallest oC DNA molecuJes; a virtually infinite number of different" genetic messages can exist.
Now we know Ihal a typical bacterial gene is made up of approximately 1, base pairs. If an indMdual has! Each chain has a molecular vveight of about 16, daltons. Two o: The l chains and P chains are ton- IroIled by distinct genes so thal a single mutation wi!! In , Vemon M. Except for this one change, Ihe entire amino acid sequence is identical in normal and mutant hemoglobin. Subsequent studies of amino aad sequences in hemoglobin isolated from other forms of anemia com- pletely supported this proposal ; sequence analysis showed Ihat each specific anemia is cr.
IlIuslralion, Irving Ceis. Rlght5 o. Not to be reprcduced vithout permission. HbO l,. ChemicaJly, it is very similar lo DNA lt, too, is a long, Wl branched molecule containing fout types of nucleotides linked logelher by 3' - 5' phosphodiesler bonds Fig- ure The first is a minor modification of the sugar component Figure Z Despite these differences, however, polyribonucleotides have the potential for rorming complementary helices of the ONA type.
Neither the addiHonal hydroxyl group. RNA is typically found in the eell as a single-stranded molecule. If double--stranded RNA heliees are formad. In , F'raneis Crick referred lo this pathway for the Dow of genetic information as tbe cenlral dogma.
Duplicatioo r;;: Correspondingly, the synt hesis of proteins translation is directed by an RNA template. Must importantl y. RNA seq11enees are never determincd by prot ejn templates. Such reversals of the [10rmal Oow of informa! Thus, the cent ral dogma as originnHy proc1e.
The Adaptor Hypmhesis of Crick Al first il seemed simples! A nOOcctide. In addltion. RNA has! The upper righl POnion shows a plYh01 01 the mltochondnon and! Sotne rbasomes e1: R Poner, shaped that only one given aroino acid would fit. By , however, Crick became disenchanted with Ihis conventional wisdom, arguing thal il would never work. Vel, t.
In the second place. Crick thus proposed Iha! The Test Tube Synthesis of Proteins The discovery of how proteins are synthesized required ihe develop- ment of cell-free extracts capable of ca.
These were first elfect ively developed beginning in by Paul C. Zamecnik aod his coll aborators. Key lo their success were the reccntl y available radioactively-tagged amino acids. I-lreparalivc for fracti onalion of their cullular extracts.
Early on, the cellular site of proteln synthesis was pinpointed lo be the ribosomes. Several years later. Zamecnik, by then collaborating with Mahlon B. To nearly everyone except Crick. Bul once Ihe ribosomes of E. First, al1 E. Ihat either stick together 01' rall apart in a reversible manner, depend- ing OD the surrounding ion coneentration.
Second, all the rRNA chains with in the small subunits are of similar ehai n lengths about 1, bases in E. Third, the base composition of both the small and Jarge rRNA chains is approximately the same hjgh in G and el in all known bacteria, plants.
This was no! Mosl strikingly. Becuuse it UlITies Ih!! This RNA shows the expected large variations in leogth, clepending 00 Ihe polypep- lides for which tbey codeo Hence, it is easy to understand why mRNA was first overlooked.
Because only a small segment oC mRNA is attachecl at a given moment to a ribosome. HoI- and his associates. I "" im Sine. When bdse pairing an amino acid camed at Ihe OIher end of! Earh ribosome anaches al a start signal at tne 5' end of an mRNA chaio and syntheslles a as it proceeds along me molecule.
In bacteria, the same enzyrne makes each of the major RNA classes ribosomal, transfer, and messengerl, using approp! Direct evidence lha! This makes sense. The synthesis oC RNA al ways proceeds in a fixed direction, beginning aJ the 5' end and c1uding with the 3'-end nucleotide fsee Figure By briefly exposi ng cells to rndioactively labelcd precur- sors, then adding a large excess oC unlabclecl amino acids a "pulse chase" experirnentl.
Establishing the Genetic Code Given the existence of 20 amioo acids bul only Cour bases. SUpenrrposed on a photograph of a thin section of the ceN is a photograph of an exposed silver emulsion.
Each dark spot represents the path of an electron emined lrom a. Courtesy of D. Prescott, Universlty of Colorado Medical Schoo! Nudeic Add Res. It held that successive groups oC nuc1eotides along a DNA chain eode Cor suecessive amino acids along a given polypep- tide chain. That colinearity does in Caet exist was shown by eIegant mutalional analysis on baelcrial proteins, carricd out in the early s by Charles Yanofsky and Sydney Brenner.
Equally important were the genetic analyses by Brenner and Crick, which in firsl established Ihal groups oC three nucJcoticles are uscd lo specify indi- vidual amino acids. The major breakthrough carne whcn Marshall Nirenberg and Hciruich Matthaci. The nucleotide groups UUU Ihus musl specify phenylalanine. Use of increasingly more eomplex, defined polynucleotides as synthetie messenger RNAs rapidly led to the identificalion oC more and more codons.
These furlher defined polynucleotides were criti- cal to test more specific sels oC codons. Completion of Ihe code in revealed that 61 out oC the 64 possible pennuted groups corresponded to amino acids. As we hl: Thi s question was answered in a classic experiment in which a ceJl-free system was used ror carrying out proteio synthesis.
The full -Icnglh polypeptides were then trealecl with an enzyme, the protease trypsin. In the final step of the experiment o the amoun! The experimental details are described in the text a Distribulion 01 radiooctMry among completcd c: Keep in mind Ihal Ihe globin ehains were al various slages of eompletion during Ihe period of Ihe pulse Figure a.
Thus, naseenl ehains Ihal had only jusi slarled lo be synlhesized would be unlikety lo have reaehed eompletion duriog Ihe period of Ihe pulse beca use Ihe time of Ihe pulse-Iabeling was less than the time required lo synlhesize a complete globin ehain.
On the other hand, globin ehains tha! AIso, keep in mind Ihat only ehains that had reaehed fulll ongth during the lime of the pulse were isolated and subjected to trypsin treatment. Iherefore, fol- lows that Ihe trypsin-genCl'atcu peptides wirh Ihe Jeast amonnl uf radioaetive amino acid normali zed lo Ihe size of the peptide should have derived from regions of Ihe globin protein thal were the first to be synlhesized.
The results of Ihe expcriment aro shown in Figure b. As you can see, radioactive labeling was lowesl for peptides from the amino- tenninal region uf globin and greatest ror peptides from lhe carboxyl- terminal region. We, therefore. In other words. But, in fact, translation bolh starts and stops at internal positions. Three sep8rate codons UAA. More compHcated is the way lranslalional slart signals are encoded. The AUe codons, at which polypeplide chains staft, are preceded by specific purine-rich blocks of nucleolides that sen 'e to altach mRNA lo ribo- sornes see Chapler This meant thal profound insighls into Ihe nature of living things aod Iheir evoJuti on would be revea ted from ONA scquences.
In recent years Ihe advent of rapid. Even the human genome, 8 single eopy of which is composed of more Ihan 3 billion base pairs, has been elucidated and shown lo contain more lhan 30, genes.
During the upcoming years , many more complete genome assemblies wil! Crogs, and dogs. In the future it should be possible to extend the interpretation oC genome sequences beyond the identification of genes and their encoded proteins. Other d asses oC ONA seqllences mediate replica- tion.
It is possi ble lo envi sion a day whao comparative DNA sequence analysis will reveal basic lnsighls into the origius of complex behavior in humans. The purpose of the forthcoming chapt ers is to provide a fiTm foundation for underslanding how DNA funetions as lho templete Cor biological complexity. The remain ing chaplers in Part 1, review the basie chemislry and biology relevant lo the main themes of this book.
Part 2, Maintenance oC the Cenome , describes the slructure of tho genetic material and as faithful duplication. Parl 3, Expression of the Genome. Part 4, Regulation, describes strnt e- gies for differentia l gene activity that are used lo generate complex- By within organisms Cor example. Finally, Part 5. Methods, descri bes various 1abaratory techniques. Walson anel Crick proposed a double-helic. Adenine is always joinecl lo [hymJne. This lrans- fonnalion is achieved in two sleps.
The key characlenstic of Ihe genctir: Knowledge of the gcnetic code allows us to predict protein coding sequences from DNA 8el: The tl dvent of rapid ONA sequendng melhods has ushered in a new ere oC genomics.
Slrelton A. Cenelic l: The nonsense tri plels for chain lerminalion and Iheir suppression. Naturo DreJUJer S.. Jacob F" aud Mesdson M. Cairns J. Cold Spring Harbar Laoomlory Press. Cold Spri ng Harbor. Slruclure and funcHon of nucleil.: Valume The complementary struclure o[ deoxyri bonucleic acid.
Soco Al Crick Y. On degcnemle templete and the adaptor hypothesis. Menlioned in Crick's discussion, pp. GlJllbridge Univers ity Press. On proteio synlhesis. The rectlnt in Ihe coding prob- lem. Whal Mad Pursuit ; Personal View of Scien- lifte Discovery.
Bflsic Rooks, New York. Operotors and Promoters: Universily or California Press. F" rankli n R. Mol ecul ar confi gura- lion in sodium thymonuch. Nalure Hershey A. Hoagland M. Seo" I,E, Hocht L. Holl ey R. Apgar J.. Everctt C. Madison I. Marquisse M. Penswick I. Slrudure or a ribonudeic acid. Ingram V. Gene ll1utati ons in human henlOglobin: The dlflmical difference betwecn normal hnd sickle r.
NaIUl"e IAcob y: Judlion H. The oighth day of creation. Expanded edHion. Kornberg A. DNA Repbcation. Freeman, New York. MeCarl ' M. The transforming principlf1: Discovering that genes are mude of ONA. New York.. Meselson M. Thc repli catioo of ONA in Escherichio eoli. Nirenoorg M. IInd MaUhflei. The uf cell-free proh: Tlle poth lo Ihe doubJe helix. University of Washington Press. Seattl e. Portugal EH. A century of DNA: MIT Press.
Sarabhai A. Co-Iineari ly of Ihe gene wilh polypeptide d lain. Slent C. MoJecular genetics: Volkin E. Phosphorus incorpora- ti ao in E. Walson J. Involvemenl of RNA in synthesis ofpro- leins. A NorlOIl criticaJ edilioll. A Passion for DNA: Genes, Genomes and Society. Genes, and Gamov: After the Double HeJix. Walson '. Genetical int plicatiolls of Iht: Nufure Molecular strudure of nucleic acids: A struclure for deoxyri bose nud eic acid.
Wilkins M. Mole- cular slruelure of deoxypenlose nucleic aei d. Noturo 1. Yanofsky C.. On the colinearily of strue- ture and prot ein slrucl urc. Covalcnt banda are strong. Weak bonds mediate the intemctions between enzymes and their substrates. But equally important. Ukewise, it is lhe weak. Olaractcristics of Olemical Bonds p. In particular we describe what iI is thal gives weak bonds their weak character.
Aggregates of finite size are called molecules. Foe example. Chemical bonds are characlerizod in several ways. An obvious charac- teristic of a bond is its strength. Strong bonds al most never Cal! Thi s ia why atoms unilod by cavalonl The Colcept 01 Free Energy p. Shown here is a portion 01 dn extended polypeptide chain.
Adapted ffOrn pauling L Copynght O Comell University. Weak bonds are easily broken, and when thcy exist singly, they exist fleetingly. Only when prcsent in ordered groups do weak bonds lasl a long lime. The strength of a bond is correlated with ils lenglh. H aro 0. AnolhElr important eharacteri stic is the maximum number oC bonds thal a given alom can make.
The number of covalent bonds that an atom can Corm is call ed its valcncc. Oxygen, for example. It can never fonn more than two covalenl bonds. There is more variability in the case of van der Waals bonds, in which lhe limiting factor is purely sleric. The number oC possible bonds is limited only by lhe number oC aloms tha1 can touch eueh other simul- taneously.
The formation of hymogen bonds is subjecl to more restric- tions. A covalentIy-bonded hydrogen atom usually participates in only one hydrogen bond.
The angle between two bonds originating CroIn a single alom is called the bond angle. The angle belween 1wo specifie covalent bonds is al ways approximately the same. Bonds differ also in the freedom ofrotation lbey allow. Single eDva- lent bonds permit free rotation oC bound atoms Figure , whereas double and tripl e bonds are quite rigid. Bonds wilh partial doubte- bond Chaf'dcter, such as the peptide bond, are also quite rigid. Much weaker. Chemical Bonds Are Explainable in Terms The nalure of the forees, both strong and weak, that give rise lo ehemical bonds remained a myslcry lo ehemists until the quanlum Iheory of the a10m quantum mechanies was developed in Ihe , Then.
Tt was realizecl that all ehemical bonds. Formation lnvolves a Change in [he Form of Energy The spontaneous formation of a bond between two atoms always involves '-he relcase of sorne of Ihe internal encrgy of the unbonded atoms and its conversion to another energy formo The stronger the bond.
The rate of the reactioJl is directl ' proportional to the frequem: