CHAPTER 4
Software (DNA) enters the computer, above, instructing it to print out hardware components from the printer, at the right.
INFORMATION
The Storehouse of Know-How
IMAGINE A COMPUTER THAT CAN BUILD ITSELF — A COMPUTER THAT CONTAINS WITHIN its software the recipe for its own assembly. Its hardware, made from the software’s instructions, handles the building, maintenance, and repair tasks. It also reads the software’s instructions. Before the computer reaches the end of its workable lifetime, the hardware makes an exact copy of the software. This begins an entirely new copy of the software. This begins an entire- ly new and duplicate computer. And the cycle repeats itself indefinitely.
A living cell is such a self-organizing system. As such, it embodies a paradox: If hardware depends on software, and software depends on hardware, how could such a process ever get started in the first place? You’ll recognize this as another version of the classic question,“Which came first, the chicken or the egg?” (see page 176).
More puzzles center on the nature of the software that life uses. For example, where does a young sapling store the information needed to build another oak tree? And how does this information interact with the rest of the tree’s hardware? In this and the next chapter, Machinery, we explore the relationship between software and hardware, between the “information” and “machinery” of life.
4.1	Why Life Must Come From Life
It is no more likely that life could suddenly arise from non-life — for exam- ple, that flies could be created by decay- ing meat — than that a 747 could accidentally be assembled by a tornado blowing through a junkyard.
Flies pose an assembly problem much tougher than a 747. They are the result of billions of years’ worth of accumulated “research and development,” i.e., informa- tion built up by trial and error. Flies, like airplanes, can’t be built without lengthy assembly instructions.
An Unbroken Chain
Throughout most of history, people believed life was controlled by mysterious, supernatural forces. For instance, seeing worms, maggots, flies, or even mice squirm- ing around in decaying grains, mud, or rotting meat convinced early scientists that life arose spontaneously from non-life. Experiments later refuted this notion, but it still took a long time to appreciate why “spontaneous generation” is impossible: Life took 4 billion years to reach its present level of complexity. To maintain it, life must always come from life, flowing from generation to generation in an unbroken chain (except at its beginning on Earth four billion years ago). This inevitable conclusion comes from our modern understanding of the key role played by the information living things store within themselves.
DOING Science
The Death of “Spontaneous Generation”
In 1668, in one of the earliest care- fully controlled biological experi- ments, Francesco Redi hypothesized that the life that was apparently gener- ated from decaying meat didn’t arise from non-life, but actually came from eggs laid on the meat. He took eight flasks with meat in them, left four open to the air, and sealed the others. After a while, maggots (fly larvae) infested the four open flasks, but none appeared in the sealed flasks. Redi then tried covering the formerly sealed flasks with gauze: no maggots. He cor- rectly concluded that the maggots had come from eggs deposited on the meat by flies. This experiment disproved the notion that visible creatures, at least, were spontaneously generated from some “vital principle” in decaying matter.
Yet people still believed that microorganisms such as bacteria and yeast sprang spontaneously from decaying matter. The controversy raged on until 1864, when Louis Pasteur determined to end it. First, he tested air and dust and showed that they contained living organisms (he called these “ferments”). Next, he added air and dust to thoroughly steril- ized materials, sealed them in flasks, and noted that life rapidly multiplied with- in. Then he placed sterilized matter inside a flask with a long S-shaped neck stopped up with a cotton plug; no life arose inside the flask. If Pasteur tipped the flask so that its contents touched the cotton plug, thereby cont- aminating them with microorganisms trapped in the plug, life sprang forth inside the flask within 48 hours. And, of course, if he broke the neck and let air in, growth inside the flask rapidly ensued.	Said	Pasteur, “Never will the doctrine of spontaneous generation recover from the mortal blow that a sim- ple experiment has dealt it.” It hasn’t.
People who held strongly to the idea of spontaneous generation were hard to convince, though. They were sure that Pasteur was not accounting for a mysterious “life force” in his experiments.
The illustrations below show the different experimental methods Pasteur used to accommodate and disprove the “life force” hypothesis.
The sequence of Pasteur’s experiments
Pasteur’s and his critics’ interpretations of the results follow the sequence.
Each experiment begins with sterilized broth. Any living things the broth may have contained are destroyed by heat.
Pasteur: The broth provides a nutrient medium for the growth of unseen organisms in the air: life comes from other life.
His critics: A sterilized broth gives rise to life: spontaneous gereration.
Pasteur: The heat has killed the microorganisms in the air.
His critics: Sealing the flask prevents entry of the "life force."
Pasteur: The heat has killed the microorganisms in the air.
His critics: Sterilizing the air kills the "life force."
Pasteur: No living thing will appear in the flask because microorganisms will not be able to reach the broth.
His critics: If the "life force" has free access to the flask, life will appear, given enough time.
Some days later the flask is still free of any living thing. Pasteur has disproved the doctrine of spontaneous generation.
DOING Science
The Germ Theory and Its Applications to Medicine and Surgery Read by Louis Pasteur before the French Academy of Sciences,April 29th, 1878.
Published in Comptes rendus de l'Academie des Sciences, lxxxvi, pp. 1037-1043.
The Sciences gain by mutual support. When, as a result of my first communications on the fermenta- tions in 1857-1858, it appeared the ferments, properly so-called, are living beings, that the germs of micro- scopic organisms abound in the surface of all objects, the theory of spontaneous generation is chimerical; that wines, beer, vinegar, the blood, urine, and all the fluids of the body undergo none of their usual changes in pure air, both Medicine and Surgery received fresh stimulation. . . .
Our researches of the last year left the etiology of the putrid disease, or septicemia, in a much less advanced condition than that of anthrax. We had demonstrated the probability that septicemia depends upon the presence and growth of a microscopic body, but the absolute proof of this important observation was not reached. To demonstrate experimentally that a microscopic organism actually is the cause of a dis- ease and the agent of contagion, I know no other way in the present state of Science than to subject the microbe . . . to the method of cultivation out of the body.
Our researches concerning the septic vibrio had not so far been convincing, and it was to fill up this gap that we resumed our experiments. To this end, we attempted the cultivation of the septic vibrio [a type of microbe] from an animal dead of septicemia. It is worth noting that all of our first experiments failed, despite the variety of culture media that we employed. Our cultural media were not sterile, but we found . . . a microscopic organism showing no relationship to the septic vibrio . . . an impurity introduced unknown to us . . . into the abdominal fluids from which we took our original cultures of the septic vib- rio. [We found] a pure culture of the septic vibrio in the heart’s blood of an animal recently dead of sep- ticemia but . . . all our cultures remained sterile.
It occurred to us that the septic vibrio might be an obligatory anaerobe [an organism that cannot sur- vive in the presence of oxygen] and that the sterility of our inoculated culture fluids might be due to the destruction of the septic vibrio by the atmospheric oxygen dissolved in the fluids. . . .
It was necessary therefore to attempt to cultivate the septic vibrio in a vacuum or in the presence of inert gases — such as carbonic acid.
Results justified our attempt; the septic vibrio grew easily in a complete vacuum, and no less easily in the presence of pure carbonic acid.
. . . It is a terrifying thought that life is at the mercy of the multiplication of these minute bodies, it is a consoling hope that Science will not always remain powerless before such enemies. . . .
Question.
What three specific steps in the scientific process does Pasteur describe in the paper above? What personal attributes of the researchers contributed to their eventual success?
Answer...
Pasteur describes an observation (specific microscopic organisms are associated with cer- tain diseases), a hypothesis (a microscopic organism is the agent of disease and contami- nation), and an experiment (the attempt to grow these organisms and, by implication, even- tually to inoculate healthy animals with it and see whether they caught the disease). The curiosity, determination, and creative imagination of the researchers shine through the description of their work.
4.2	An Abbreviated History of Genetic Discoveries
Uncovering the Secrets of Heredity
Once scientists realized that life can only come from life, they began to look more closely at inheritance. Yes, our offspring look like us...but why?
This short survey takes us up to the 1940s.
1860s
 “Factors” Determine Inheritance
Austrian monk Gregor Mendel discovers that something he dubs “fac- tors” somehow determine inheritance in pea plants. Every trait appears to be con- trolled by a pair of these factors. Further, a trait may have “dominant” and “recessive” forms. For instance, if Mendel bred a tall plant with a short one, the off- spring were mostly tall; tallness is domi- nant, and shortness recessive. However, the recessive trait isn’t lost — it can reap- pear in a later generation; two tall pea plants bred together might produce a short one.
Mendel’s work remained largely unread until around 1900.
1890s Chromosomes
Chromosomes, microscopic structures in the cell nucleus, are discovered by many researchers. They note that chro- mosomes, which come in pairs, double before cell division and are then shared between daugh- ter cells. It is suspected that chromosomes are the carriers of heredity.
1903 “Factors” Are on Chromosomes
William Sutton makes the connection between Mendel’s factors and chromosomes. One member of each pair of trait-deter- mining factors is on one of a pair of chromosomes. One chromosome comes from the mother’s egg, and the other from the father’s sperm.
1905 Chromosomes Actually Determine Inheritance
Edmund B. Wilson and N. M. Stevens discover that a particular chromosome called the X chromosome, of which there are two in female cells and one in male cells, determines the sex of the offspring and explains why there are equal numbers of females and males: All eggs have an X, but only half of sperm do (the other half get a Y chromosome). This is the first evidence that a specific chromosome carries a specific hereditary property (sex).
1906 Mendel’s “Factors” Are Genes
Scientists coin the term “gene,” meaning a piece of genetic information specifying a particular trait or characteristic. Genes are the factors Mendel discovered.
Genes Are Inherited Together
Thomas Hunt Morgan shows that many genes are inher- ited together, as would be expected if they are linked to each other in chromosomes. (The fruitfly has four chro- mosomes, and it has four groups of linked genes.) Chromosomes, then, are chains of genes.
1908 Genes Are Lined Up Along Chromosomes
Morgan observes that even though genes tend to be inherited togeth- er, this occurs more frequently with some pairs than with others. He infers that the farther apart genes are on a chromosome, the less likely they are to be inherited together. (This is because an actual physical exchange of genes takes place between chromosomes.) Morgan is able to “map” the rela- tive positions of genes along fruitfly chromosomes.
1909 Hereditary Diseases May Be Caused by Defective Genes
Archibald Garrod postulates that certain inheritable human diseases result when particular proteins fail to perform their normal function.
1927 New Traits Are Caused by Mutations
Scientists realize that mutations — changes in genes — are what pro- duce new genetic characteristics (as well as inherited diseases). They further realize that without mutations, there can be no evolu- tion (see Chapter 8, Evolution). Hugo de Vries had discovered genetic mutations in 1886. Hermann Muller first produces mutations with X-rays in 1927.
1942 One Gene — One Protein
George Beadle and Edward Tatum, using bread molds, show that individual genes con- trol production of individual proteins (see page 149).
1944 Natural Selection Operates on All Living Things
Salvador Luria shows that bacteria are subject to the same genetic and evolutionary forces that operate on plants and animals.
Bacteria, because they reproduce so rapidly, become the main experimental subject of molecular genetics.
Genes Are Made of DNA
Oswald Avery and associates show that genes are made of deoxyribonucleic acid — DNA.
4.3	Life’s Coding and Decoding Systems The Recipe and The Cake
Here we’ve listed some instances of the relationship between encoded “ideas” and their decoded “products.”
Idea
Blueprint
Recipe
Menu
Sheet Music
Genes
Product
Building
Cake
Meal
Symphony
Proteins
We can consider the items in the left- hand column as chunks of information corresponding to the actual products in the right-hand column. But, strictly speaking, coded information also exists in material form — ink, paper, molecules — so the items on the left are also products.
Rocks are simple, stable arrange- ments of molecules settled into low- energy states.
A toad’s cells are complex arrangements of high-energy mole- cules, dynamically organized by information.
Information Is Embedded in Living Things
A fundamental difference between living and non-living things is that living things use information to create and maintain themselves. Rocks contain no instructions on how to be rocks. Toads contain instructions on how to be toads.
Information, like ideas, is dimensionless. It’s simply a comparison between one thing and another, a registering of differences. Information becomes tangible when it is encoded in sequences of symbols: zeros and ones, dots and dashes, letters of the alphabet, musical notes, etc. Such sequences of symbols, in turn, are decoded — by machinery or by us — into computer output, Morse code messages, books, sym- phonies, etc. In order to be stored or transmitted, then, information needs to be put into some physical form, a process that requires energy. In this sense, you might say that “mind” and “matter” are inextricably linked.
Life’s information — the “ideas” governing how it operates — is encoded in sequences of nucleotides (genes), which are, in turn, decoded by machinery (pro- teins) that manufactures parts that work together to make a living creature. Like the computer that builds itself, the process follows a loop: Information needs machinery, which needs information. This relationship can start simply and then, over many generations, build into something complex. Similarly, our deeper thoughts evolve out of simpler bits and pieces — hunches, ideas, memories.
Information Needs Difference
A chain that simply repeats one symbol carries no useful information.
But a chain made up of different sym- bols can encode information. All of life’s genetic instructions are spelled out in combinations of four different “letters.”
4 different nucleotides
4.4	DNA — What Does It Actually Say?
Not a Blueprint But a Recipe
We might never understand life’s complexity were it not for the discovery that life is orchestrated by “intelligent” worker molecules called proteins. These proteins are various combinations of twenty, and only twenty, different amino acid molecules linked together into chains of various lengths. Every unique function of a protein is determined by the order of the amino acids in its chain.
Here we have a powerful insight into the way life works: One chain, DNA, car- ries information; a second chain, of amino acids linked into proteins, does life’s work of growing, maintaining itself, and reproducing. DNA’s sequence of units deter- mines the sequence of amino acid units in proteins. Thus, DNA is not like a blue- print, which contains an image or a scale model of the final product; it is more like a recipe — a set of instructions to be followed in a particular order.
So life’s complexity arises from a breathtaking simplicity: DNA’s message says, “Take this, add this, then add this...stop here. Take this, add this, then add this,...etc.” While the idea is simple, accomplishing it requires some ingenious machinery (see Chapter 5).
DOING Science
A Key Discovery: One Gene Makes One Protein — Beadle and Tatum and Bread Mold
GeorgeW.BeadleandEdward L.Tatum.1941. Genetic control of biochemical reactions in Neurospora. Proc. Nat.Acad. Sci. 27: 499-506.
Most of the inherited traits studied up to the early 1940s were complex functions: height of pea plants, fruitflies’ wing shape or eye color, etc. These were probably controlled by many genes.
George Beadle realized he had to narrow the focus — to find one simple trait controlled by one spe- cificgene.InspiredbyThomas Morgan, he started working with fruitflies but soon found a better subject — the common bread mold Neurospora. Here’s the kind of experiment he and his associate, Ed Tatum, did. Normal molds can convert sugar, step-by-step, into all twenty amino acids. For instance, amino acid Z is made by convert- ing molecule A into molecule B, then B into C, and finally C into Z. Beadle and Tatum exposed molds to X-rays, causing them to change — to mutate — so they and their progeny could no longer make cer- tain amino acids. One mutant could no longer make Z unless BeadleandTatumsupplieditwith molecule C. Giving it A or B didn’t help. They concluded that the mutant had lost the ability to con- vert B to C — in other words, X-rays had damaged the protein (an enzyme) that converts B to C. Another mutant was unable to make Z unless it was supplied with molecule B. Beadle and Tatum concluded that this mutant had lost its ability to convert A to B — that is, X-rays had damaged the protein that converts A to B. Beadle and Tatum correctly surmised that each mutant had sustained X-ray dam- age to a specific gene that was responsible for making a specific protein. This simple idea — that one gene codes for one protein — opened the door to deeper under- standing of how genes work.
Cooking Up a Fruitfly
The recipe for a fruitfly (Drosophila melanogaster) produces an organism with an extraordinarily complex life cycle. As you can see in the illustration, the process of getting from a fertilized egg to an adult fly is no simple matter. The “stop here,” “start there,” “take this,” “add this” instructions in a fruitfly’s DNA are translated into machinery that builds several very different forms along the way to adulthood and egg-laying. During the fly’s life cycle, a fertilized egg, essentially a sac with single nucleus in it, becomes a wormlike form, the larva, which is eventually transformed into a winged, six-legged adult capable of producing eggs or sperm that can combine to form fertilized eggs. Each fertilized egg contains all the instructions it needs to assemble the next generation.
The egg, about one-third the size of an adult fruitfly, carries in its DNA the genetic recipe needed to produce all the forms in the fly’s life cycle. That means not just the instructions for making the parts but also those for making them at the right time and in the right sequence! Genes containing the instructions for making wings and legs can’t be active in the larval stages. When one set of instructions is being implemented, the others are on hold, temporarily inactive.
As the egg develops, groups of genes turn on and off in response to chemical signals produced by other genes, and the first-stage larva is eventually formed. It grows and molts, becoming a second-stage larva. Then, after a second molt, the instructions that assemble larvae shut down, and those for making a pupa become active. While a larva is growing, it develops little patches of cells called imaginal discs, shown at left. These remain dormant until instructed to grow in the pupal stage, when they begin to develop into adult structures. In the laboratory, this entire cycle takes only 10–14 days from start to finish.
A Look at the Basic Ingredients
Let’s take a closer look at part of the assembly process. The road to adulthood begins when the single fertilized nucleus in the egg forms a cluster of nuclei that subsequently migrate to the inner surface of the egg. Two basic types of cells form around these naked nuclei. One type consists of a single layer of cells that forms around the periphery of the egg. These will become body cells. The other group of cells, called pole cells, forms at one end of the egg. Pole cells are destined to become the cells that will pass on instructions to the next generation. Genetic changes (mutations) that occur in these cells will become part of the next generation’s set of instructions — changing the recipe. If the change is advantageous to the offspring, the process of evolution will tend to keep the revised recipe in the cookbook. If the change is detrimental, as changes most often are, the offspring of the adult formed from this egg will not survive or will not reproduce as well as other individuals. The change will be lost over time. That particular version of the recipe will go out of print.
Find the fruitfly
This	is the actual size of an adult fruitfly. You can imagine how small its egg is! Yet that egg contains all the instructions needed to make not only several larval stages and a pupa but also the adult’s eyes, mouthparts, wings, antennae, reproductive organs, and hundreds of other parts.
The fertilized nucleus
The egg cell’s nucleus contains one set of genes from each parent — two copies of the same recipe. In biology, as in other things, variety is the spice of life, and biological variety arises in part from the fact that no two recipes are exactly the same. The overall instructions give similar results, but one recipe may yield a fly with red eyes and another a fly with white eyes. Differences in instructions are worked out during development. Variety allows evolution to test new genetic “ideas.”
Nuclear migration
Nuclei migrate to the periphery and are surrounded either by pole cells or by the single layer of cells that will develop into the fruitfly’s body parts.
(A)	Stage 1 Newly laid fertilized egg (0-15 min)
(B)	Stage 2 Early cleavage (15–80 min)
(C)	Stage 3 Pole-cell formation (80–90 min)
(D)	Stage 4 (90–150 min)
(E)	Stage 5 Cellularization (150–180 min)
4.5	Nucleotides — Letters on a Backbone
Chemical Units of Information
Like the letters in the words of this paragraph, the four nucleotides of DNA comprise the letters of its language — the language of heredity. Each of the four nucleotides consists of a base, a sugar, and a phosphate.The base is either adenine (A), thymine (T), cytosine (C), or guanine (G) — each one a unique arrangement of carbon, nitrogen, oxygen, and hydrogen atoms.The base is bonded to a deoxyribose sugar, shown in all illustrations as a white cylinder, and to a phosphate. Like beads strung in a necklace, the repeating phosphate-sugar parts of the nucleotides link to each other in a continuous backbone that holds the sequence in order.
From Nucleotide to Genome — A Hierarchy of Packaging
A nucleotide
Smallest informational unit, which, by itself, conveys no message
A letter
A triplet
3 nucleotides that specify one amino acid (also called a codon)
A word
A string of letters that conveys a unit of meaning
A gene
A string of triplets that specifies a protein
A paragraph
A string of words that conveys an idea
Like the letters in the words of this paragraph, the four nucleotides of DNA comprise the letters of its language — the language of heredity. Each of the four nucleotides consists of a base, a sugar, and a phosphate. The base is either adenine (A), thymine (T), cytosine (C), or guanine (G) — each one a unique arrangement of carbon, nitrogen, oxygen, and hydrogen atoms. The base is bonded to a deoxyribose sugar, shown in all illustrations as a white cylinder, and to a phosphate. Like beads strung in a necklace, the repeating phosphate-sugar parts of the nucleotides link to each other in a continuous backbone that holds the sequence in order.
A chromosome
A spooled-up string of genes (about 3000) packaged in a single unit
One volume
A genome
All of the chromosomes of a single organism — usually collected in the nucleus of each of its cells
A set of volumes
DOING Science
A Chemical Can Genetically Change Cells
It took many years of laborious chemical analysis and the painstaking development of methods for purifying and testing cell components before Oswald Avery, Colin MacLeod, and Maclyn McCarty at the Rockefeller Institute in New York announced, in 1944, that the transforming agent was DNA (until this time, protein was thought to be the hereditary material). Their work confirmed that DNA is the genetic molecule; genes are made of DNA.
In 1928, Frederick Griffith, a London medical officer, made a momentous discovery. At that time, the major cause of death worldwide was lobar pneumonia, caused by the pneumococcus bacterium. Scientists knew that certain mutant forms of these bacteria were benign; i.e., they didn’t cause disease. Griffith discovered that if he mixed these living harmless pneumococci with dead disease-causing pneumococci and
injected the mixture into mice, the mice all died of pneumonia. Moreover, their bodies were teeming with living, multiplying killer pneumococci! Something had been released from the dead killer cells and got inside the living benign cells and changed their inheritance; harmless cells had been permanently transformed into killer cells by engulfing the DNA of the dead killer cells. What was this transforming substance? Griffith was never to know — he died in the bombing of London in 1941.
1.	The nucleotides adenine and thymine...
2.	...go together in a perfect fit.
4.6	DNA — Base Pairs and Weak Bonds
Nucleotide Pairs — A Key to Structure and Function
DNA is always found as a double chain, one lineup of different nucleotides paired with another. As you can see in the illustrations, the base parts of the four nucleotides (marked A,T, G, and C) match up in pairs. Their shapes and chemical make-up are such that A fits only with T and G fits only with C. These pairs, when fitted together, have exactly the same width (the distance from sugar to sugar). So the sequence of nucleotides in one chain of DNA will exactly match a complementary sequence in the other chain — and the backbones of the two chains will always be exactly the same distance apart. For example, if the sequence of nucleotides on one side is G-T-A-C-C, the sequence on the other side is C-A-T-G-G.
DOING Science
Moving In on the Structure of DNA
James Watson and Francis Crick, who began to work together in Cambridge, England, in 1951, believed that if they could visualize the form of a DNA molecule, they might see how it carried information and how it made copies of itself. They already knew a lot about DNA’s chemistry timeline. DNA was first discovered by Johann Miescher in Switzerland back in 1869, and, over the years, many chemists had identified its four nucleotides and found out how they were linked in a chain. Furthermore, in 1949, Irwin Chargaff, a	pairs of nucleotides showed this conchemist at Columbia University in	sistent relationship. What structure New York, had shown that while	could account for this property? samples of DNA taken from different organisms — animals, plants, yeast, or bacteria — contained different amounts of the four nucleotides, the amount of adenine in each sample always equaled the amount of thymine, and the amount of guanine always equaled the amount of cytosine.At the time, no one knew why the quantities of these
3.	The nucleotides guanine and cytosine...
One chain is a counterpart, or complement, of the other. Note, too, that because of the way A and T or G and C must match up, the two chains must have opposite chemical directions — indicated at right by the opposing arrows.
Nucleotide pairing enables the two chains of DNA to fit together perfectly.
Hydrogen Bond
Things come together easily..4.
...also go together in a perfect fit.
...and break away easily.
Weak Bonds
Weak bonds make it possible for big molecules to change shape or come apart and rejoin. Twenty times weaker than the covalent bonds that hold atoms together in molecules, these weak attractions between positive and negative charges can form only at very close range. Such weak bonds hold A to T and G to C in DNA and allow the two chains to separate readily, which they must do to replicate themselves.
4.7	DNA — The Double Helix
Information with a Twist
DNA resembles a spindly ladder that has been twisted so that its sides form spirals. Its exceeding thinness means it can easily be packed into small places. Its doubleness ensures that it won’t get tangled up in itself; and it also protects the precious inward-facing nucleotide sequence — DNA’s letters — from damage. And, as we shall see, this doubleness is what allows DNA to be copied.
Bacteria carry their DNA in one long double helix. In our cells, the DNA resides within the nucleus in 46 chromosomes — 46 double-stranded helices. The chains are stupefyingly long: If we think of the links in each DNA chain as letters, bacterial DNA represents about 60 average novels; human DNA about 1500! If all of the DNA in one of our cells was laid out end to end, it would be about 2 yards long. For a double chain that long to fit into a space as small as a cell nucleus, it must be incredibly thin and thus capable of folding and wrapping its strands up into dense, small structures. Since we have about 5 trillion cells, the total length of DNA in each of us would reach the 93 million miles from here to the Sun 30 times.
DOING Science
Watson and Crick Discover the Structure of DNA
In London in 1952, Maurice Wilkins	and	Rosalind Franklin were using a process called X-ray diffraction (see page 13) to examine the shape of DNA. They shone X-ray beams through DNA and recorded on photographic film the pattern of scattering caused by the DNA molecules. Their work suggested that DNA was in the form of two or three chains whose bases somehow stacked near one another.
At Cambridge, Watson and Crick made cardboard and then sheet metal cut-outs of the nucleotides, based in part on knowledge obtained by Rosalind Franklin and Maurice Wilkins. This model-building approach was a key to their ultimate success.
A big eye-opener came when Watson and Crick learned that the molecular shapes of DNA’s nucleotides were such that adenine fit only with thymine, and guanine fit only with cytosine. This made sense of Chargaff’s discoveries (page 154). WhenWatson and Crick “mated” these base pairs inside DNA’s sugar-phosphate backbones in a double helix, everything fit beautifully.
Watson and Crick triumphantly presented their model to the scientific world in 1953. Its acceptance was immediate, not only because of its intrinsic elegance but because it at once suggested how DNA could replicate itself: One strand was a complementary copy of the other; if the two strands were separated, new nucleotides could be laid down along each to form new strands (see page 159).

4.8	DNA — Creating Its Own Future
Doubling of Information
Before a cell divides to become two, its DNA must be doubled so that each daughter cell will receive a perfect copy. This means the strands of DNA must first be separated, then com- plementary nucleotides must be linked along each of the separated strands.
DNA Replication — The Basic Idea
A double strand of DNA...
...“unzips” like a zipper, making its nucleotide bases accessible.
Free-floating nucleotides (made in other parts of the cell match with their complements...
...and link up, the original strand serving as a template (pattern) for the new.
Thus, a new strand is formed along each of the open strands. In this way, a single DNA molecule becomes two.
4.9	How Enzymes Copy DNA
The “Initiator”	The “Unzipper”	The “Builders”	The “Eraser”	The “Untwister”	The “Straighteners” The “Stitcher” (initiator protein)	(helicase)	(polymerases)	(repair nuclease)	(topoisomerase)	(single-strand DNA-	(ligase) binding proteins)
A Cast of Ingenious Characters
The sequence at the left oversimplifies. DNA doesn’t copy itself any more than a recipe bakes a cake. DNA passively stores information. The team of proteins (enzymes) shown above and found in all self- replicating organisms does the actual copying, or replication. They do it with an accuracy of only one mistake in every hundred thousand or so nucleotides!
DNA Replication — The Details
1. The initiator finds the place to begin copying and guides the unzipper to the correct position.
2. The unzipper separates the DNA strands by breaking the weak bonds between the nucleotides.
3. Then the builders arrive to assemble a new DNA strand along each of the exposed strands.
4. They build by joining individual nucleotides to their matching complements on the old strand.
5. Free-floating nucleotides bring their own energy.
6. As each new nucleotide is added to the growing chain, its phosphate bond energy goes into making the new bond.
7. The upper builder follows behind the unzipper, but the lower strand runs the opposite way.
8. Yet the lower builder must build in the same chemical direction. She solves this by making a loop...
9. ...and building along the bottom half of it.
10. When she finishes a length, she lets go of the completed end...
11. ...grabs a new loop, and continues linking nucleotides along a new stretch.
12. So, while the top new strand is built continuously, the bottom new strand is assembled in short lengths…
13. ...which are then spliced together by the stitcher. This reaction requires energy, supplied by ATP.
14. The straighteners keep the single DNA strands from getting tangled.
15. And the untwister unwinds the double helix in advance of the unzipper.
16. The initiator (1), the unzipper (2), the builders (3), the stitcher (4), the untwister (5), and the straighteners (6) work together in tight coordination, making near-perfect copies at the rate of fifty nucleotides per second!
4.10 Genomes
It has become increasingly clear that full disclosure of the language genes speak — the sequence of their nucleotide paragraphs — is essential to clarifying how their protein and RNA products interact in health and disease. We can now envision the eventual successful prevention or treat- ment of large numbers of purely genetic diseases, as well as major illness like cancer, cardiovascular disease, diabetes, multiple sclerosis, and Alzheimer’s. And gene sequencing can be expec- ted to improve the nutritional value and disease resistance of crops. From a more basic research perspective, gene sequencing will continue to probe deeper into the evolutionary and present relationships of humans to all other living creatures and into how we grow, develop, and function. With the advent of tech- niques to be described in the following pages, and with ever increasing computer capacity,scientists have come to realize it would actually be possible to determine the full sequence of letters in the human genome — all three billion of them. It has long be recognized that each species has its own unique sequence of genes. Between any two humans, for example, there are many differences within their genes but there is only one order of genes common to all — only one “human genome.”
The completion of the sequencing of the human genome is only the beginning. For once we know all the letters in the paragraphs and books, we must still find out what they mean — what are the protein products of those genes, how do they inter- act with and control each other, and how does their failure to function compromise our health.
Right now, we don’t even know how many genes are in the human genome. Estimates range from 40 thousand to 120 thousand, and we’re a long way from knowing what their functions are. Furthermore, only about 5% of our genome is genes. The function of the other 95% of our DNA is unknown.
Identifying DNA’s Uniqueness
Simple viral genomes were the first to be sequenced. Then, in 1996, a yeast, Saccharomyces cerevisiae, which has fewer than 7000 genes (about 13 million nucleotides) was sequenced. In 1997, researchers announced that the sequence of the common intestinal bacterium Escherichia coli, which has about 4300 genes (more than 4 million nucleotides). Less than two years later, scientists reported that the first animal genome had been sequenced. Caenorhabditis elegans, a millimeter-long nematode (worm) that has nearly 1000 cells as an adult, (see the illustration, top right) and some 20,000 genes (97 million nucleotides). Researchers are currently working on the genomes of a number of other organisms.
C. elegans
(magnified 130 times)
This minuscule worm’s genome prescribes the types and arrangements of its thousand or so cells into all the body parts you see here.
Success in moving on will continue to come from the study of simple models — simpler organisms. In the case of C. elegans, researchers have identified functions for less than half of the nearly 20,000 genes. They plan to selectively inactivate by muta- tion each of the remaining genes in an attempt to determine what it does. And sequencing of the mouse genome is nearing completion, which should speed up annotation of the human genome. Not only do the mouse genome and the human genome has approximately the same number of nucleotides (about 3 billion), but mouse genet- ics has been studied extensively for years and the functions of many genes have already been described.
Nearly every great scientific or technolog- ical advance carries the potential for both great good and great harm; genetic engineering, a tool already widely used in pharmaceutical manufacturing and plant science, is no excep- tion. Critics worry, however, that genetically engineered organisms will have unforeseen effects on other organisms and the environ- ment. And the potential for deliberate intro- duction of genetically engineered super- pathogens can’t be dismissed lightly. Genetic engineering isn’t going to go away, however; in fact, its potential has only begun to be tapped.
Reading Genomes — The Technology: 1
A length of DNA from any chosen source can be inserted into the DNA of liv- ing bacteria and copied repeatedly as the bacteria multiply. The discovery of this technique, called recombinant DNA technology, opened the door in the mid-1970s to the modern era of genetic engineering. In practice, the subject DNA is first spliced into the DNA of a plasmid — a wandering virus-like piece of DNA that enters bacterial cells and replicates in synchrony with them (see pages 324–325). In a couple of days, millions of bacteria will have accumulated and their millions of copies of passenger DNA can be extracted and studied.
A new technique now in widespread use because it is faster and readily automa- ted is PCR — polymerase chain reaction. It makes use of DNA polymerase*, the enzyme in all living cells that makes DNA. It will copy as little as a single molecule of DNA from any source: such as body tissues and fluids, disinterred bodies, pre- served prehistoric specimens, etc. The process involves the following steps:
1.	The subject DNA to be copied (up to some 5000 nucleotides in length) is heated to separate the two strands.
2.	Short stretches of RNA (5–20 nucleotides in length) called primers** syn- thesized to be complementary to short DNA stretches at either end of the subject DNA, are added.
3.	Polymerase and lots of the four nucleoside triphosphates complete the mix.
4.	Synthesis of new DNA proceeds to completion along each of the separated subject strands, starting from the primers at either end. This results in two double strands. The cycle is repeated: reheating to separate the strands and adding more nucleoside triphosphates (free nucleotides) and primers.
So we start with a test tube containing the four kinds of nucleotides, a couple of primers, some Taq polymerase, and a sample of DNA, and we subject it to several dozen PCR cycles. What have we got? We have millions of copies of the targeted section of the sample DNA.The targeted section could be a gene or part of a gene, a mutation or infective viral or bacterial material. All nontargeted parts of the original DNA are essentially invisible after such extensive amplification. PCR is so sensitive that it can make copies from degraded DNA of miniscule cell fragments.
PCR has been used to study the DNA of mummies, extinct animals, and even an amber-encased termite from 3 million years ago. Researchers managed to extract some DNA from Neandertal bones, amplify it with PCR, and compare it with the DNA of modern humans.Their conclusion? Neandertals were not our ancestors; they diverged genetically from our ancestors 500,000 to 600,000 years ago. PCR is now used every day for many other laboratory applications, including, for example, routine forensic investigations, HIV detection when infection levels are very low, and amplification of unexpressed DNA molecules for cloning or genetic engineering.
**RNA primers are essential for DNA synthesis by DNA polymerase in nature and in the test tube. An enzyme called RAN polymerase first builds a short primer complementary RNA onto a chain to be copied. The DNA polymerase then initiates synthesis from the primer. The primer is later removed and replaced with DNA nucleotides. This step was omitted for simplification from the description of DNA synthesis on pages 158–161. The need for primers poses a limitation to PCR. To make them, the chemist must know the sequence of bases at either end of the subject DNA.
DNA Fingerprinting — The Technology: 2
All living creatures, and even members of the same species, have their own, unique, DNA text. Identifying an individual’s DNA depends on demonstrating differences in nucleotide sequences. Fingerprinting human DNA focuses on stretches of nucleotides that are particularly variable from one person to another — called VNTRs: variable numbers of tandem repeats. (Five to ten percent of the human genome consists of these stretches of as few as two to as many as several thousand nucleotide sequences repeated over and over. Their function is unknown.)
VNTRs are snipped into smaller pieces by restriction enzymes. These are enzymes from bacteria that cut DNA double strands at particular short sequences of nucleotides — each enzyme recognizing and cutting at one and only one short sequence.
If several restriction enzymes are used to snip DNA in several different locations, a number of fragments will be produced of varying lengths. The number and lengths of the fragments depend on which restriction enzymes are used.
The fragments need next to be separated and visualized. This is done by gel electrophoresis. The chopped-up DNA samples are placed on the top of a gel — a sheet of jello-like material through which the fragments migrate. (Movement of the frag- ments, which are negatively changed, is in response to an electrical field through the gel — positive at the bottom.) The shorter the fragments, the faster and farther they move.
The gel sheet with the fragments now separated is treated to convert the fragments’ double strands to single. It is then pressed against — blotted onto — a sheet of nylon to which the single strands stick. The fragments are made visible by annealing them with single-strand radioactive DNA fragments (called DNA probes). These bind to their complements on the nylon sheet and, when the sheet is laid onto photographic film, show up on the film as dark bands.
The human genome yields, by both these methods, distinctive patterns of bands — distinctive fingerprints.
The apparatus
The gel acts a bit like a fine sieve. It’s easier for small frag- ments to move through the sieve than it is for large ones, so the larger DNA fragments lag behind smaller ones as they progress through the gel.
The outcome track
The dye binds to the DNA fragments, whose sizes are then measured by their positions along the gel track. Fragments of the same DNA line up with one another; fragments of differing DNA line up differently.
Using DNA Fingerprinting
Aside from its obvious uses in forensic analysis and legal proceedings, DNA finger- printing is used to determine parentage (of animals and plants, as well as humans), to assess donor-recipient compatibility, and to optimize mate selection for captive endan- gered species. Patent cases involving genetically engineered or selectively bred organ- isms have been settled by DNA fingerprinting. The technique has also been used to track the source of Caspian caviar in an effort to protect nearly extinct species of stur- geon, and to identify the origin of hides, tusks, and meat in cases of suspected poaching. DNA from ancient plant, animal, and human remains has been analyzed for informa- tion on species and population evolution.
In December 1999, French scientists began DNA testing on the preserved heart of the presumed Dauphin Louis XVII of France, whose parents (the king and queen, Louis XVI and Marie-Antoinette) were guillotined in 1793 at the height of the French
Revolution. The child was reported to have died in prison two years after his parents were executed, but numerous rumors of his escape surfaced over the years, and a number of persons claimed to be him or one of his descendants. The heart of the boy who died in prison, which had been removed and pre- served at autopsy, changed hands a number of times but ended up at the royal crypt of the Saint-Denis cathedral outside Paris. DNA from Marie-Antoinette’s hair follicle cells and from those of two of her sisters were compared with DNA from the pre- served heart and from two of the sisters’ known living descendants. The comparison confirmed that the heart was indeed that of the unlucky ten-year-old.
Comparing the “fingerprints”
Here you see DNA fragments from one person compared to those from another. Column V shows the DNA of a stabbing victim. Column D shows the DNA of a suspect in the stab- bing. The columns labeled “jeans” and “shirt” are DNA from blood cells found on the suspect’s clothing. What can you infer from this compari- son?
The discoveries of Science, the works of art, are explorations — more, are explosions, of a hidden likeness. Jacob Bronowski, Science and Human Values, 1956
Reading a Gene Sequence — The Technology: 3
Here is one way DNA sequencing is performed.
DNA is cut into lengths of a few hundred nucleotides by restriction enzymes. These are separated into single strands. Four reaction tubes are set up by containing:
1.	The single-strand DNA.
2.	The four nucleotides ATP, GTP, CTP, and TTP.
3.	A primer complementary to the first few nucleotides of the DNA. This is made radioactive so that the sequence of nucleotides added to it may be detected at the end of the reaction.
4.	The enzyme DNA polymerase.
5.	And, in each tube, a small amount of a chemically altered form of either
ATP or GTP or CTP orTTP. These are chain stoppers. DNA synthesis proceeds. The enzymes add nucleotides, one by one, starting from the primer, each new nucleotide complementary to a nucleotide on the DNA strand being copied. Whenever one of the chain-stopper nucleotides enters the chain synthesis stops. This produces newly made single strands whose lengths depend on how many nucleotides got into the chain before lengthening stopped. The lengths of chains is determined by gel electrophoresis as in fingerprinting. This method is so exquisitely sensitive it can separate sequences of 100 or more nucleotides that differ in length by only one nucleotide. For example, using a primer of 10 nucleotides, in the tube containing chain-stop-per GTP, sequences of length 11, 14, 17, and 19 are found. We conclude that the new sequence added to the 10 nucleotide primer had G in positions 1, 4, 7, and 9. In the tube containing chain-stopper CTP, sequences of length 13, 15, and 18 are found. This means C must occupy positions 3, 5, and 8. Similarly, the tubes containing chain stoppers ATP and TTP show A to be in position 2 and 10 and T to be in position 6.
We conclude that the sequence of the copy made in this run is: GACGCTGCGA.
Once this sequence is revealed, the complementary sequence of the input DNA is known.
There are now ways to automate this whole process so that thousands of nucleotides can be sequenced daily!
4.11	DNA Repair
1. The eraser finds and then chews out the defective nucleotide.
2. The builder then replaces it with an energized nucleotide.
This forms a bond on one side but leaves a gap on the other.
A Precise, Self-Correcting System
Although the system for copying DNA is extremely accurate, mistakes do hap- pen; sometimes these mistakes can be devastating. Other threats to the integrity of DNA, which regularly damage nucleotides, include chemical events inside cells and ultraviolet light. The cell recruits an army of repair enzymes to handle these prob- lems. Three kinds of repair enzymes regularly patrol DNA and repair any errors they find. First, erasers find poorly matching or damaged nucleotides and snip them out. Second, builders follow close behind to fill the gaps, using the other strand as a guide. Finally, stitchers restore the continuity of the backbone of the repaired strand.
Cells have evolved repair enzymes to help them survive those natural processes that regularly damage DNA. These enzymes continuously scan DNA and replace miscopied or damaged nucleotides.
3. The stitcher closes the gap using ATP for energy.
4.12	Permanent Changes in DNA
DNA has its own efficient repair mechanisms; however, sometimes even those mechanics can't do the job. The result is a mutation — a permanent change in the genetic material. Mutations can range from inconsequential to advantageous, inconvenient to fatal. The type of cell affected (germ cells, like eggs or sperm, versus all other somatic cells), the stage of development, and the recessiveness or dominance of the mutated gene are the determining factors.
Some mutations are spontaneous (which means they generally have unknown causes, but are often the result of replication errors during cell division); others are induced by exposure to some agent (such as cer- tain chemicals and types of radiation) known to be a mutagen — a “hacker” that inserts, deletes, or rearranges a section of DNA code. If this occurs in a gene (instead of in the long “junk” sequences between genes), the substitution of even a single base pair can have serious consequences; sickle-cell ane- mia is a classic example (see page 51). You'll recall that each gene is the recipe for a specific protein. Proteins are made up of amino acids, and each of the 20 amino acids is specified by three nucleotides. In effect, a series of three-letter words (codons) makes up the paragraph that is the recipe for a particular pro- tein.	An insertion or a deletion, unless it is a multiple of three nucleotides, changes every codon from that point on to the end of the gene. Fortunately, the ratio of “junk” to protein-coding DNA segments is very large, about 95 to 1 in mammals, and most mutations have no detectable effects.
Mutations, as you recall from Chapter 2, play both advantageous and damaging roles, depending on their environment (Life Creates With Mistakes, see pages 47–49). An example given there is of various snow-dwelling species whose protective white coloration is a mutation that provides an advantage in a snowy landscape.
Spontaneous mutations are at the root of much of the selective breeding done by animal (and plant) fanciers. Witness the many breeds of domestic dogs — all belong to the same species (Canis familiaris), but they vary amazingly in size, shape, color, and coat. Some of this variability is just part of the genome, of course. But over the years, certain mutations popped up (an unusual color, perhaps, or a longer or shorter coat) and were selectively bred for.
Standing out
You might wonder why this penguin, white among his darker brethren, stands alone on the Antarctic ice. Shouldn't his white coloration protect him and show up in many of his descendants? Alas, no. Antarctic penguins have no predators on land, where this one blends into the background. Underwater, though, he stands out like a McDonald’s sign for the whales, sharks, and seals looking for fast food.
Life's few really bad mistakes tend not to live at all, or to die very soon, and thus don't get incorporated into the organism’s gene pool. Somatic mutations although they can seriously affect an individual organism, don't ever make it into the gene pool (except through cloning). Germ-cell mutations are the ones that are passed along to the next generation. In cells that have DNA from two parents, a mutated gene can be either dominant or recessive. Dominant genes are always expressed whether the parental genes are the same or dif- ferent, but recessive genes are expressed only when genes from both parents are the same. Many inherited diseases — cystic fibrosis is one — are due to mutated recessive genes that can be passed along for generations with no expression. Only when a carrier of such a gene mates with another carrier of that gene does the possibility for expression of disease exist, and even then an individual offspring has only a one in four chance of inheriting the recessive gene from both parents.
Just such a chance occurrence provided a means for studying immune system biology. In 1980, four laboratory mice came to the attention of an immunologist when their blood tests suggested that they had no immune reactions. As a result of a spontaneous muta- tion in one of their parents,the four littermates lacked the ability to makeT and B cells, the white blood cells that fight disease and reject transplants. Today, the scid (severe combined immunodeficiency) mouse is essential to AIDS studies and donor/host tissue rejection research. The scid mouse can be implanted with human tissue, and thus human diseases, and will not reject the implants. Researchers can then experiment with various drug regimens and even gene therapy.
Like mice, fruitflies have been used for years in laboratory research. One of the first species to have its embryonic genes manipulated extensively, the fruitfly was mutated in the lab to produce, for example, myriad eye and wing variations as well as body part rearrangements. But the fruitfly is an invertebrate. The new kid on the block, a vertebrate, is the zebrafish (Danio rerio).
The field is developmental biology, and the goal is to find the genes responsible for building the vertebrate embryo. A freshwater aquarium fish, the zebrafish (see page 257) is very hardy and has a 3-month life span. Its embryo is transparent, which allows researchers to observe every step of embryogenesis (which takes only 5 days), including nervous system development. Mutations are easily induced by exposing breeding adults to chemicals, viruses, or radia- tion. Many of these mimic human diseases and defects. Locating the precise gene affected, then cloning it, is the next step. One researcher, Nancy Hopkins at MIT, discovered that using viruses to induce mutations provided a ready-made label on the mutated gene. The potential benefits of fully under- standing how vertebrate embryos develop are not lost on biotechnology firms, which are vying to fund zebrafish research.
Sensitive cats
Siamese cats, bred for their coloration, have a “conditional mutation”; its expression depends on temperature. The enzyme responsible for black coloration is tempera- ture-sensitive and inactive at normal body temperature. Black pigment is deposited in the hairs only on the cooler regions of the body: face, ears, paws, and tail. The mutation gave rise to the breed.
Doing Science
A single gene can have a much larger effect than you might think, when you’re told that all a gene does is to make a protein — as this study shows.
Ferguson, J. N., Young, L. J., Hearn, E. F., Marzuk, M. M., Insel, T. R., and Winslow, J. T. 2000. Social amnesia in mice lacking the oxytocin gene. Nature Genetics, 25.
For mice and other rodents, smell is the primary “social sense.” Unlike humans, for whom visual cues are primary guides in social behavior, mice depend on olfactory cues to tell them whether other mice are familiar to them, inter- ested in them, or hostile to them. This paper studies the effect of a single gene, the one that makes the brain pro- tein oxytocin, on the social memory of mice.
Mice without the oxytocin gene are perfectly capable of responding to nonsocial olfactory stimuli, such as the smell of food or of a familiar place, but they don’t respond to familiar mice. They suffer from social amnesia. When these mutant, oxytocin-deficient mice were treated with oxytocin, their social memory was “rescued,” and when normal mice were treated with a substance that inhibited the action of oxytocin, they developed social amnesia.

4.13	DNA to RNA: Copying Genes into Messengers
Transcription: Preparing the Daily Work Orders
While replication of DNA is the grand event preceding a cell’s division into two, DNA also regularly participates in the daily business of living. As in our imaginary self-assembling computer, DNA’s software provides the instructions to its hardware. These instructions get sent out from DNA’s central storehouse in the cell nucleus to the protein-making assembly plants in the cell’s cytoplasm (see Chapter 5, Machinery), in the form of gene messengers, short stretches of information copied off the DNA. Messengers are made of a sort of throw-away version of DNA — good for limited work but not for long-term storage. Imagine going into a vault, taking out a set of precious instructions written on fine parchment, carefully copying the part you need on ordinary paper, returning the parchment to the vault, and then carrying the copy to the factory floor.
This process, called transcription, represents only the first stage of a larger operation dedicated to making proteins. You might notice (on the right-hand page) that transcription shares some of the mechanics of replication: DNA’s double helix gets opened up, and a new nucleotide chain is built along a pre-existing strand that acts as a guide, or template. But the two processes differ. Transcription involves copying only one or a few genes at a time, not thousands. And the new, throw-away molecule that is produced is mRNA (ribonucleic acid), a close cousin to DNA.
In the large cells of eukaryotes, the precious DNA is kept safe within the nucleus.
Rather than risk moving its DNA, the cell makes a disposable copy of the pertinent gene(s) — a messenger RNA — which it then dispatches to the protein assembly site.
But to make proteins, DNA’s instructions must reach the factories out in the cell’s cytoplasm.
Making a Messenger — The Basic Idea
First, a small section of DNA is opened up.
One strand conveys the actual message of the gene.
The other strand acts as a template on which the messenger is made.
The messenger is made of nucleotides, similar to how DNA is built.
As the messenger is assembled, it separates from the template strand.
And when the entire gene is copied, the DNA releases the messenger.
Messenger-building requires the work of a single versatile enzyme.
It finds the starting point along DNA...
...copies the gene...
...and then closes the double helix.
The egg contains all the information needed to.....make a new chicken…
4.14	The Chicken/Egg Problem
A New Way to Look at an Old Paradox
Untangling the chicken/egg problem (“Which came first?”) produces some real insight into the way life works. The paradox plays a trick by seeming to ask a single question when in fact it asks two very different questions at the same time. The first deals with cycles, the second with evolution. We need to separate these two.
We begin with the simple observation that any true loop has no beginning and no end. Chicken produces egg, egg produces chicken — in an endlessly repeating cycle. So the answer to “Which came first?” must be “neither.” If you want to understand the underlying mechanism, however, try looking at the chicken as machinery and the egg as information. Machinery makes information, which instructs machinery, etc. But this, too, oversimplifies. While it’s true that the egg has all the information needed to make the chicken, information by itself cannot do anything without some decoding machinery, i.e., the proteins required to “unpack” that information.
This DNA contains all the information needed to...
...which grows up and...
...make all the proteins for an individual chicken.
...makes a new egg...
...and so on.
“A hen is only an egg’s way of making another egg.”
—SAMUEL BUTLER
So we can say with more accuracy that the egg has all of the information plus just enough machinery to turn that information into living substance. In other words, every egg needs a little bit of chicken to go with it. The adult chicken, on the other hand, carries 100 percent of the information plus 100 percent of the machinery (that is, a complete chicken body); so producing a new egg is no problem.
The second question of the paradox might be rephrased as “Where did the chicken/egg cycle come from?” If we traced the ancestry of chicken and egg (both relatively recent “inventions”) all the way back through billions of years, what would we find at the starting point? We can’t be sure of the answer, but it may have been molecules that could function as both information and machinery (see page 292). From this beginning, chicken-ness would have arisen in steps, mostly tiny and gradual, over vast stretches of time.
Some of these proteins make more DNA... ...and so on.
4.15	DNA Packaging Blowing in the Wind
DNA has found a wealth of ingenious ways to package itself; to create carriers that ensure that its message will get to the next generation: pollen, nuts, seeds, spores, sperm, egg, etc. These vehicles often carry food with them to sustain the early phases of new lives. They also contain enough of the necessary machinery for DNA to get a new foothold — to express itself in the form of the next generation’s protein molecules.
Most of these vehicles for DNA will get lost before they find the proper environment in which to develop. Their substance will be broken down into simple molecules, and their message lost. To ensure that this won’t be the fate of all, life, profligate with energy and materials, makes millions of DNA carriers so that a few will succeed in getting their message through. However, sometimes even large numbers aren’t enough to get the job done. Over eons of trial and error, the DNA of some kinds of organisms has found ways of using other kinds of organisms to help it pass its message down the generations. A plant’s DNA, for example, instructs the plant’s flower to produce nectar to attract bees or birds, which, in the process of nourishing themselves, not only ensure the survival of their own DNA but also pick up the flower’s DNA-containing pollen and carry it to new locations. Think of the DNA of one kind of organism, then, as having the power to enlist the help of the DNA of another kind of organism to accomplish the crucial job of re-creating itself in the next generation.
Some of the Things You Learned About in Chapter 4
amino acids 148 base pairs 154 bases 152 chromosomes	145, 153 controlled biological experiments 141–143 deoxyribose 152
DNA	156, 170 DNA fingerprinting 166 factors 144 gene sequencing 168–169 genes 145 genomes	152, 164 germ theory 143 hereditarydiseases 145,172–173
information 147 inheritance 144 messenger RNA 174 mutations 172 nucleotides 152–155 one gene/one protein 149 PCR 164–165 recombinant DNA 164 replication 158–161 spontaneous generation 141–143 transcription 174
weak bonds 155 X and Y chromosomes 144
Questions About the Ideas in Chapter 4
1.	Information theorists tell us that all information, no matter what kind, depends on one simple feature. What is that feature?
2.	People refer to genes for eye color, for height, and even for certain kinds of behaviors. But literally speaking, genes have only one function. What is it?
3.	You may have heard DNA characterized as the blueprint for life. Why is this metaphor inaccurate? What’s a better one?
4.	The DNA in every cell copies itself before division. True or false?
5.	Which came first, the chicken or the egg? Explain your answer.
6.	Identify an everyday example where the shape, sequence, or arrangement of symbols transmits information for dynamic events or processes.
7.	What might be the advantage of having complementary base sequences in the two strands of a DNA molecule?
8.	If you were making a piece of furniture, you might want specific tools for each step of the job (i.e., a saw, hammer, drill press, mitre box, and router) rather than just one small, all-purpose hand tool. What is the advantage of having “dedicated” tools for a job? What are the “dedicated” tools of DNA replication?
9.	If all life comes from life (there is no spontaneous generation) and the cell is the basic unit of life, then how could the first cell have arisen?
References and Great Reading
Beadle, G.W. and E. L.Tatum,1941. Genetic control of biochemical reactions in Neurospora. Proc. Nat. Acad. Sci. 27: 499-506.
Dawkins, R. 1990. The Selfish Gene. Oxford: Oxford University Press. Hartl, D. and Jones, E. 2001. Genetics:Analysis of Genes and Genomes. 5E.
Sudbury, MA: Jones and Bartlett Publishers. Krings, M.,A. Stone, R.W. Schmitz, H. Krainitzki, M. Stoneking, and S. Paabo, 1997. Neandertal DNA
sequences and the origin of modern humans. Cell 90:19. Mullis, K.B. 1990. The unusual origin of the polymerase chain reaction. Scientific American 262(4):56-61,
64-65. Pasteur, L. 1878. The Germ Theory and Its Applications to Medicine and Surgery. Comptes rendus de
l'Academie des Sciences, lxxxvi, pp. 1037-43. Watson, J. D. and F. H. C. Crick, 1953. Genetical implications of the structure of deoxyribonucleic acid.
Nature. 171: 964-967.
Watson, J. D. and F. H. C. Crick, 1953 Molecular structure of nucleic acids – a structure for deoxyribose nucleic acids. Nature. 171: 737-738.
“The red fox can run far.” Like nucleotide codons, the three-letter words in this sentence convey information. Describe the effect on information content of each of the following actions: (1) Delete a single letter from the first word and shift the following letters over by one so that the words continue to have three letters. (2) Delete a single letter from the last word and shift the remaining letters of the following words over by one so that the words continue to have three letters. (3) Substitute the letter m for the letter r. (4) Add the letter m to the start of the second word and shift the following letters over by one so that the remaining words continue to have three letters.
Question.
How does deleting letters or changing the groupings of the letters in this sentence (while keeping them in the same order) change the information content of the sentence? What does this have to do with DNA base sequences and the function of proteins?
Answer...
Changing the grouping of letters as well as the kinds and numbers of letters alters the amount of information transmitted. This is equally true for words in a sentence and for DNA base sequences. Altering the genetic code changes the kinds of proteins made and may alter or destroy protein function.
1. Her edf oxc anr unf ar. No information remains because the words are not understandable after the deletion.
2. The red fox can run fr. Most information is preserved up to the point of the deletion, so the sentence makes some sense even though it is incomplete.
3. The med fox can mun fam. A few words are understandable, but the entire sentence is not.
4. The mre dfo xca nru nfa r. No information is conveyed.
WEB Connection
For more questions and links to web resources, go to
www.jbpub.com/connections
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