Isoborneol -

3-Ketobutyryl-protein
PROBLEM Propose a mechanism for the biosynthesis of the sesquiterpenoid trichodiene from farnesyl 27-48 diphosphate. The process involves cyclization to give an intermediate secondary carbocation, followed by several carbocation rearrangements.
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Farnesyl diphosphate (FPP)
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Isoborneol -

Trichodiene


CHAPTER 28 -

Biomolecules: Nucleic Acids
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1013.jpg?height=1031&width=1879&top_left_y=357&top_left_x=242)


CHAPTER 28 -

FIGURE 28.1 If these Afghan hounds look similar, that's because they're identical-all cloned from somatic cells of the same donor. (credit: modification of work "Figure 1" in "Birth of clones of the world's first cloned dog" by Kim, M.J., Oh, H.J., Kim, G.A. et al./Sci Rep 7, 15235 (2017), CC BY 4.0)


CHAPTER CONTENTS -

28.1 Nucleotides and Nucleic Acids
28.2 Base Pairing in DNA
28.3 Replication of DNA
28.4 Transcription of DNA
28.5 Translation of RNA: Protein Biosynthesis
28.6 DNA Sequencing
28.7 DNA Synthesis
28.8 The Polymerase Chain Reaction


CHAPTER CONTENTS -

WHY THIS CHAPTER? Nucleic acids are the last of the four major classes of biomolecules we'll consider. So much has been written and spoken about DNA in the media that the basics of DNA replication and transcription are probably known to you. Thus, we'll move fairly quickly through the fundamentals and then look more closely at the chemical details of DNA sequencing, synthesis, and metabolism. This field is moving rapidly, and there's a lot you may not be familiar with.


CHAPTER CONTENTS -

The nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are the chemical carriers of a cell's genetic information. Coded in a cell's DNA is the information that determines the nature of the cell, controls its growth and division, and directs biosynthesis of the enzymes and other proteins required for cellular functions.


CHAPTER CONTENTS -

In addition to nucleic acids themselves, nucleic acid derivatives such as ATP are involved as phosphorylating agents in many biochemical pathways, and several important coenzymes, including NAD ${ }^{+}$, FAD, and coenzyme A, have nucleic acid components. See TABLE 26.3 for their structures.


CHAPTER CONTENTS - 28.1 Nucleotides and Nucleic Acids

Just as proteins are biopolymers made of amino acids, the nucleic acids are biopolymers made of nucleotides, joined together to form a long chain. Each nucleotide is composed of a nucleoside bonded to a phosphate group, and each nucleoside is composed of an aldopentose sugar linked through its anomeric carbon to the nitrogen atom of a heterocyclic purine or pyrimidine base.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1014.jpg?height=589&width=1465&top_left_y=622&top_left_x=327)


The sugar component in RNA is ribose, and the sugar in DNA is $2^{\prime}$-deoxyribose. (In naming and numbering nucleotides, numbers with a prime superscript refer to positions on the sugar and numbers without a prime superscript refer to positions on the heterocyclic base. Thus, the prefix $2^{\prime}$-deoxy indicates that oxygen is missing from C2' of ribose.) DNA contains four different amine bases: two substituted purines (A, adenine, and G, guanine) and two substituted pyrimidines ( $\mathbf{C}$, cytosine, and $\mathbf{T}$, thymine). Adenine, guanine, and cytosine also occur in RNA, but thymine is replaced in RNA by a closely related pyrimidine base called $\mathbf{U}$, uracil.
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Ribose
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1014.jpg?height=215&width=256&top_left_y=1492&top_left_x=802)


Uracil (U) RNA


The structures of the four deoxyribonucleotides and the four ribonucleotides are shown in FIGURE 28.2. Although similar chemically, DNA and RNA differ dramatically in size. Molecules of DNA are enormous, containing as many as 245 million nucleotides and having molecular weights as high as 75 billion. Molecules of RNA, by contrast, are much smaller, containing as few as 21 nucleotides and having molecular weights as low as 7000 .
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1015.jpg?height=353&width=461&top_left_y=203&top_left_x=672)


2'-Deoxyadenosine 5'-phosphate
Deoxyribonucleotides


C
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1015.jpg?height=359&width=427&top_left_y=661&top_left_x=681)


2'-Deoxycytidine 5'-phosphate

2'-Deoxyguanosine 5'-phosphate


T


Adenosine 5'-phosphate
Ribonucleotides
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1015.jpg?height=358&width=438&top_left_y=1656&top_left_x=670)


Guanosine 5'-phosphate


Uridine $5^{\prime}$-phosphate


FIGURE 28.2 Structures of the four deoxyribonucleotides and the four ribonucleotides.
Nucleotides are linked together in DNA and RNA by phosphodiester bonds [ $\mathrm{RO}-\left(\mathrm{PO}_{2}{ }^{-}\right)-\mathrm{OR}$ '] between phosphate, the $5^{\prime}$-hydroxyl group on one nucleoside, and the $3^{\prime}$-hydroxyl group on another nucleoside. One end of the nucleic acid polymer has a free hydroxyl at C3' (the $\mathbf{3}^{\prime}$ end), and the other end has a phosphate at $\mathbf{C 5}^{\prime}$ (the $\mathbf{5}^{\prime}$ end). The sequence of nucleotides in a chain is described by starting at the $5^{\prime}$ end and identifying the bases in order of occurrence, using the abbreviations G, C, A, T (or U in RNA). Thus, a typical DNA sequence might be written as TAGGCT.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1016.jpg?height=608&width=950&top_left_y=189&top_left_x=582)


PROBLEM Draw the full structure of the DNA dinucleotide AG. 28-1

PROBLEM Draw the full structure of the RNA dinucleotide UA.
28-2


CHAPTER CONTENTS - 28.2 Base Pairing in DNA

Samples of DNA isolated from different tissues of the same species have the same proportions of heterocyclic bases, but samples from different species often have greatly differing proportions of bases. Human DNA, for example, contains about $30 \%$ each of adenine and thymine and about $20 \%$ each of guanine and cytosine. The bacterium Clostridium perfringens, however, contains about $37 \%$ each of adenine and thymine and only $13 \%$ each of guanine and cytosine. Note that in both examples the bases occur in pairs. Adenine and thymine are present in equal amounts, as are cytosine and guanine. Why?


In 1953, Rosalind Franklin, Maurice Wilkins, James Watson, and Francis Crick published scientific reports describing the secondary structure of DNA. According to their model, DNA under physiological conditions consists of two polynucleotide strands, running in opposite directions and coiled around each other in a double helix like the handrails on a spiral staircase. The two strands are complementary rather than identical and are held together by hydrogen bonds between specific pairs of bases, A with $T$ and $C$ with $G$. That is, whenever an A base occurs in one strand, a T base occurs opposite it in the other strand; when a C base occurs in one, a G occurs in the other (FIGURE 28.3). This complementary base-pairing thus explains why A and $T$ are always found in equal amounts, as are $G$ and $C$.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1017.jpg?height=280&width=527&top_left_y=253&top_left_x=360)
A
T
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1017.jpg?height=370&width=765&top_left_y=216&top_left_x=973)
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1017.jpg?height=334&width=513&top_left_y=703&top_left_x=353)
G


FIGURE 28.3 Hydrogen-bonding between base pairs in the DNA double helix. Electrostatic potential maps show that the faces of the bases are relatively neutral, while the edges have positive and negative regions. Pairing $G$ with $C$ and $A$ with $T$ brings together oppositely charged regions.


A full turn of a DNA double helix is shown in FIGURE 28.4. The helix is $20 \AA$ wide, there are 10 base pairs per turn, and each turn is 34 Å in length. Notice in FIGURE 28.4 that the two strands of the double helix coil in such a way that two kinds of "grooves" result, a major groove $12 \AA$ wide and a minor groove $6 \AA$ wide. The major groove is slightly deeper than the minor groove, and both are lined by flat heterocyclic bases. As a result, a variety of other polycyclic aromatic molecules are able to slip sideways, or intercalate, between the stacked bases. Many cancer-causing and cancer-preventing agents function by interacting with DNA in this way.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1017.jpg?height=860&width=1294&top_left_y=1500&top_left_x=405)


FIGURE 28.4 A turn of the DNA double helix in both space-filling and wire-frame formats. The sugar-phosphate backbone runs along the outside of the helix, and the amine bases hydrogen bond to one another on the inside. Both major and minor grooves are visible.


An organism's genetic information is stored as a sequence of deoxyribonucleotides strung together in the DNA chain. For the information to be preserved and passed on to future generations, a mechanism must exist for
copying DNA. For the information to be used, a mechanism must exist for decoding the DNA message and implementing the instructions it contains.


What Crick called the "central dogma of molecular genetics" says that the function of DNA is to store information and pass it on to RNA. The function of RNA, in turn, is to read, decode, and use the information received from DNA to make proteins. This view is greatly oversimplified but is nevertheless a good place to start. Three fundamental processes take place.


- Replication is the process by which identical copies of DNA are made so that information can be preserved and handed down to offspring.
- Transcription is the process by which genetic messages are read and carried out of the cell nucleus to ribosomes, where protein synthesis occurs.
- Translation is the process by which the genetic messages are decoded and used to synthesize proteins.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1018.jpg?height=204&width=953&top_left_y=711&top_left_x=613)


WORKED EXAMPLE 28.1 -


Predicting the Complementary Base Sequence in Double-Stranded DNA -

What sequence of bases on one strand of DNA is complementary to the sequence TATGCAT on another strand?


Strategy -

Remember that A and G form complementary pairs with T and C , respectively, and then go through the sequence replacing A by T, G by C, T by A, and C by G. Remember also that the $5^{\prime}$ end is on the left and the $3^{\prime}$ end is on the right in the original strand.


Solution -

Original: (5') TATGCAT (3')
Complement: (3') ATACGTA (5') or (5') ATGCATA (3')


Solution -

PROBLEM What sequence of bases on one strand of DNA is complementary to the following sequence on 28-3 another strand?
(5') GGCTAATCCGT (3')


Solution - 28.3 Replication of DNA

DNA replication is an enzyme-catalyzed process that begins with a partial unwinding of the double helix at various points along the chain, brought about by enzymes called helicases. Hydrogen bonds are broken, the two strands separate to form a "bubble," and bases are exposed. New nucleotides then line up on each strand in a complementary manner, A to T and G to C , and two new strands begin to grow from the ends of the bubble, called the replication forks. Each new strand is complementary to its old template strand, so two identical DNA double helices are produced (FIGURE 28.5). Because each of the new DNA molecules contains one old strand and one new strand, the process is described as semiconservative replication.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1019.jpg?height=819&width=1308&top_left_y=176&top_left_x=403)

FIGURE 28.5 A representation of semiconservative DNA replication. The original double-stranded DNA partially unwinds, bases are exposed, nucleotides line up on each strand in a complementary manner, and two new strands begin to grow. Both strands are synthesized in the same $5^{\prime} \rightarrow 3^{\prime}$ direction, one continuously and one in fragments.


Solution - 28.3 Replication of DNA

Addition of nucleotides to the growing chain takes place in the $5^{\prime} \rightarrow 3^{\prime}$ direction and is catalyzed by the DNA polymerase enzyme. The key step is the addition of a nucleoside $5^{\prime}$-triphosphate to the free $3^{\prime}$-hydroxyl group of the growing chain with the loss of a diphosphate leaving group.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1019.jpg?height=739&width=1641&top_left_y=1254&top_left_x=242)


Solution - 28.3 Replication of DNA

Because both new DNA strands are synthesized in the $5^{\prime} \rightarrow 3^{\prime}$ direction, they can't be made in exactly the same way. One new strand must have its $3^{\prime}$ end nearer a replication fork, while the other new strand has its $5^{\prime}$ end nearer the replication fork. What happens is that the complement of the original $5^{\prime} \rightarrow 3^{\prime}$ strand is synthesized continuously in a single piece to give a newly synthesized copy called the leading strand, while the complement of the original $3^{\prime} \rightarrow 5^{\prime}$ strand is synthesized discontinuously in small pieces called Okazaki fragments (named for Tsuneko Okazaki, in recognition of her discovery of them) that are subsequently linked by DNA ligases to form the lagging strand.


Solution - 28.3 Replication of DNA

The magnitude of the replication process is staggering. The nucleus of every human cell contains 2 copies of 22 chromosomes plus an additional 2 sex chromosomes, for a total of 46 . Each chromosome consists of one very large DNA molecule, and the sum of the DNA in each of the two sets of chromosomes is estimated to be 3.0 billion base pairs, or 6.0 billion nucleotides. Despite the size of these enormous molecules, their base sequence
is faithfully copied during replication. The entire copying process takes only a few hours and, after proofreading and repair, an error gets through only about once per 10 to 100 billion bases. In fact, only about 60 of these random mutations are passed on from parent to child per human generation.


Solution - 28.4 Transcription of DNA

As noted previously, RNA is structurally similar to DNA but contains ribose rather than deoxyribose and uracil rather than thymine. RNA has three major types, each of which serves a specific purpose. In addition, there are a number of small RNAs that appear to control a wide variety of important cellular functions. All RNA molecules are much smaller than DNA, and all remain single-stranded rather than double-stranded.


Solution - 28.4 Transcription of DNA

- Messenger RNA (mRNA) carries genetic messages from DNA to ribosomes, small granular particles in the cytoplasm of a cell where protein synthesis takes place.
- Ribosomal RNA (rRNA) complexed with protein provides the physical makeup of the ribosomes.
- Transfer RNA (tRNA) transports amino acids to the ribosomes, where they are joined together to make proteins.
- Small RNAs, also called functional RNAs, have a variety of functions within the cell, including silencing transcription and catalyzing chemical modifications of other RNA molecules.


Solution - 28.4 Transcription of DNA

The genetic information in DNA is contained in segments called genes, each of which consists of a specific nucleotide sequence that encodes a specific protein. The conversion of that information from DNA into proteins begins in the nucleus of cells with the synthesis of mRNA by transcription of DNA. In bacteria, the process begins when RNA polymerase recognizes and binds to a promoter sequence on DNA, typically consisting of around 40 base pairs located upstream ( 5 ') of the transcription start site. Within the promoter are two hexameric consensus sequences, one located 10 base pairs upstream of the start and the second located 35 base pairs upstream.


Solution - 28.4 Transcription of DNA

Following formation of the polymerase-promoter complex, several turns of the DNA double helix untwist, forming a bubble and exposing 14 or so base pairs of the two strands. Appropriate ribonucleotides then line up by hydrogen-bonding to their complementary bases on DNA, bond formation occurs in the $5^{\prime} \rightarrow 3^{\prime}$ direction, the RNA polymerase moves along the DNA chain, and the growing RNA molecule unwinds from DNA (FIGURE 28.6). At any one time, about 12 base pairs of the growing RNA remain hydrogen-bonded to the DNA template.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1020.jpg?height=527&width=1606&top_left_y=1509&top_left_x=254)


Solution - 28.4 Transcription of DNA

FIGURE 28.6 Biosynthesis of RNA using a DNA segment as a template.
Unlike what happens in DNA replication, where both strands are copied, only one of the two DNA strands is transcribed into mRNA. The DNA strand that contains the gene is often called the sense strand, or coding strand, and the DNA strand that gets transcribed to give RNA is called the antisense strand, or noncoding strand. Because the sense strand and the antisense strand in DNA are complementary, and because the DNA antisense strand and the newly formed RNA strand are also complementary, the RNA molecule produced during transcription is a copy of the DNA sense strand. That is, the complement of the complement is the same as the original. The only difference is that the RNA molecule has a U everywhere that the DNA sense strand has a T.


Solution - 28.4 Transcription of DNA

Another part of the picture in vertebrates and flowering plants is that genes are often not continuous segments of the DNA chain. Instead, a gene will begin in one small section of DNA called an exon, then be interrupted
by a noncoding section called an intron, and then take up again farther down the chain in another exon. The final mRNA molecule results only after the noncoded sections are cut out of the transcribed mRNA and the remaining pieces are joined together by spliceosome enzymes. The gene for triose phosphate isomerase in maize, for instance, contains eight noncoding introns accounting for approximately $70 \%$ of the DNA base pairs and nine coding exons accounting for only $30 \%$ of the base pairs.


Solution - 28.4 Transcription of DNA

PROBLEM Show how uracil can form strong hydrogen bonds to adenine.
28-4
PROBLEM What RNA base sequence is complementary to the following DNA base sequence?
28-5
(5') GATTACCGTA (3')


Solution - 28.4 Transcription of DNA

PROBLEM From what DNA base sequence was the following RNA sequence transcribed?
28-6
(5') UUCGCAGAGU (3')


Solution - 28.5 Translation of RNA: Protein Biosynthesis

The primary cellular function of mRNA is to direct the biosynthesis of the thousands of diverse peptides and proteins required by an organism-as many as 150,000 in a human. The mechanics of protein biosynthesis take place on ribosomes, small granular particles in the cytoplasm of a cell that consist of about $60 \%$ ribosomal RNA and $40 \%$ protein.


The specific ribonucleotide sequence in mRNA forms a message that determines the order in which amino acid residues are to be joined. Each "word," or codon, along the mRNA chain consists of a sequence of three ribonucleotides that is specific for a given amino acid. For example, the series UUC on mRNA is a codon directing incorporation of the amino acid phenylalanine into the growing protein. Of the $4^{3}=64$ possible triplets of the four bases in RNA, 61 code for specific amino acids and 3 code for chain termination. TABLE 28.1 shows the meaning of each codon.


|  |  | Third base ( 3 ' end) |  |  |  |
| :---: | :---: | :---: | :---: | :---: | :---: |
| First base (5' end) | Second base | U | C | A | G |
| U | U | Phe | Phe | Leu | Leu |
|  | C | Ser | Ser | Ser | Ser |
|  | A | Tyr | Tyr | Stop | Stop |
|  | G | Cys | Cys | Stop | Trp |
| C | U | Leu | Leu | Leu | Leu |
|  | C | Pro | Pro | Pro | Pro |
|  | A | His | His | Gln | Gln |
|  | G | Arg | Arg | Arg | Arg |
| A | U | Ile | Ile | Ile | Met |
|  | C | Thr | Thr | Thr | Thr |


| TABLE 28.1 Codon Assignments of Base Triplets |  |  |  |  |  |  |  |
| :--- | :---: | :---: | :---: | :---: | :---: | :---: | :---: |
| Third base (3' end) |  |  |  |  |  |  |  |
| First base (5' end) | Second base | U | C | A | G |  |  |
|  | A | Asn | Asn | Lys | Lys |  |  |
|  | G | Ser | Ser | Arg | Arg |  |  |
| G | U | Val | Val | Val | Val |  |  |
|  | C | Ala | Ala | Ala | Ala |  |  |
|  | A | Asp | Asp | Glu | Glu |  |  |


The message embedded in mRNA is read by transfer RNA (tRNA) in a process called translation. There are 61 different tRNAs, one for each of the 61 codons that specify an amino acid. A typical tRNA is single-stranded and has roughly the shape of a cloverleaf, as shown in FIGURE 28.7. It consists of about 70 to 100 ribonucleotides and is bonded to a specific amino acid by an ester linkage through the $3^{\prime}$ hydroxyl on ribose at the $3^{\prime}$ end of the tRNA. Each tRNA also contains on its middle leaf a segment called an anticodon, a sequence of three ribonucleotides complementary to the codon sequence. For example, the codon sequence UUC present on mRNA is read by a phenylalanine-bearing tRNA having the complementary anticodon base sequence GAA. [Remember that nucleotide sequences are written in the $5^{\prime} \rightarrow 3^{\prime}$ direction, so the sequence in an anticodon must be reversed. That is, the complement to $\left(5^{\prime}\right)$-UUC- $\left(3^{\prime}\right)$ is ( $\left.3^{\prime}\right)$-AAG- $\left(5^{\prime}\right)$, which is written as $\left(5^{\prime}\right)$-GAA- $\left(3^{\prime}\right)$.]
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1022.jpg?height=1088&width=1448&top_left_y=1375&top_left_x=333)

FIGURE 28.7 Structure of a tRNA molecule. The tRNA is a roughly cloverleaf-shaped molecule containing an anticodon triplet on one "leaf" and an amino acid unit attached covalently at its $\mathbf{3 '}^{\prime}$ end. The example shown is a yeast tRNA that codes for phenylalanine. The
nucleotides not specifically identified are chemically modified analogs of the four common nucleotides.
As each successive codon on mRNA is read, different tRNAs bring the correct amino acids into position for enzyme-mediated transfer to the growing peptide. When synthesis of the proper protein is completed, a "stop" codon signals the end, and the protein is released from the ribosome. This process is illustrated in FIGURE 28.8.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1023.jpg?height=931&width=1305&top_left_y=394&top_left_x=402)


FIGURE 28.8 A representation of protein biosynthesis. The codon base sequences on mRNA are read by tRNAs containing complementary anticodon base sequences. Transfer RNAs assemble the proper amino acids into position for incorporation into the growing peptide.


WORKED EXAMPLE 28.2 -


Predicting the Amino Acid Sequence Transcribed from DNA -

What amino acid sequence is coded by the following segment of a DNA coding strand (sense strand)?
(5') CTA-ACT-AGC-GGG-TCG-CCG (3')


Strategy -

The mRNA produced during translation is a copy of the DNA coding strand, with each T replaced by U . Thus, the mRNA has the sequence
(5') CUA-ACU-AGC-GGG-UCG-CCG (3')
Each set of three bases forms a codon, whose meaning can be found in TABLE 28.1.


Solution -

Leu-Thr-Ser-Gly-Ser-Pro.


Solution -

PROBLEM List codon sequences for the following amino acids:
28-7 (a) Ala
(b) Phe
(c) Leu
(d) Tyr

PROBLEM List anticodon sequences on the tRNAs carrying the following amino acids.
28-8
(a) Ala
(b) Phe
(c) Leu
(d) Tyr


Solution -

PROBLEM What amino acid sequence is coded by the following mRNA base sequence?


CUU-AUG-GCU-UGG-CCC-UAA -

PROBLEM What is the base sequence in the original DNA strand on which the mRNA sequence in Problem 28-10 28-9 was made?


CUU-AUG-GCU-UGG-CCC-UAA - 28.6 DNA Sequencing

A scientific revolution is now under way in molecular biology, as scientists learn how to manipulate and harness the genetic machinery of organisms. None of the extraordinary advances of the past several decades would have been possible, however, were it not for the discovery in 1977 of methods for sequencing immense DNA chains.


The first step in DNA sequencing is to cleave the enormous chain at known points to produce smaller, more manageable pieces, a task accomplished by the use of restriction endonucleases, or restriction enzymes. Each different restriction enzyme, of which more than 4000 are known and approximately 600 are commercially available, cleaves a DNA molecule at a point in the chain where a specific base sequence occurs. For example, the restriction enzyme AluI cleaves between $G$ and $C$ in the four-base sequence AG-CT. Note that the sequence is a palindrome, meaning that the sequence ( $5^{\prime}$ )-AGCT-( $3^{\prime}$ ) is the same as its complement ( $3^{\prime}$ )-TCGA-( $5^{\prime}$ ) when both are read in the same $5^{\prime} \rightarrow 3^{\prime}$ direction. The same is true for other restriction endonucleases.


If the original DNA molecule is cut with another restriction enzyme having a different specificity for cleavage, still other segments are produced whose sequences partially overlap those produced by the first enzyme. Sequencing all the segments, followed by identification of the overlapping regions, allows for complete DNA sequencing.


A dozen or so different methods of DNA sequencing are now available, and many others are under development. The Sanger dideoxy method is among the most frequently used and was the method responsible for first sequencing the entire human genome of 3.0 billion base pairs. In commercial sequencing instruments, the dideoxy method begins with a mixture of the following:


- The restriction fragment to be sequenced
- A small piece of DNA called a primer, whose sequence is complementary to that on the $3^{\prime}$ end of the restriction fragment
- The four 2'-deoxyribonucleoside triphosphates (dNTPs)
- Very small amounts of the four $2^{\prime}, 3^{\prime}$-dideoxyribonucleoside triphosphates (ddNTPs), each of which is labeled with a fluorescent dye of a different color (A $2^{\prime}, 3^{\prime}$-dideoxyribonucleoside triphosphate is one in which both $2^{\prime}$ and $3^{\prime}-\mathrm{OH}$ groups are missing from ribose.)
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1024.jpg?height=326&width=394&top_left_y=1669&top_left_x=605)


A 2'-deoxyribonucleoside triphosphate (dNTP)
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1024.jpg?height=281&width=394&top_left_y=1670&top_left_x=1115)

A 2', 3'-dideoxyribonucleoside triphosphate (ddNTP)


DNA polymerase is added to the mixture, and a strand of DNA complementary to the restriction fragment begins to grow from the end of the primer. Most of the time, only normal deoxyribonucleotides are incorporated into the growing chain because of their much higher concentration in the mixture, but every so often, a dideoxyribonucleotide is incorporated. When that happens, DNA synthesis stops because the chain end no longer has a $3^{\prime}$-hydroxyl group for adding further nucleotides.


When reaction is complete, the product consists of a mixture of DNA fragments of all possible lengths, each terminated by one of the four dye-labeled dideoxyribonucleotides. This product mixture is then separated according to the size of the pieces by gel electrophoresis (Section 26.2), and the identity of the terminal dideoxyribonucleotide in each piece-and thus the sequence of the restriction fragment-is determined by
noting the color with which the attached dye fluoresces. FIGURE 28.9 shows a typical result.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1025.jpg?height=521&width=1641&top_left_y=260&top_left_x=242)

FIGURE 28.9 The sequence of a restriction fragment determined by the Sanger dideoxy method can be read simply by noting the colors of the dye attached to each of the various terminal nucleotides.


So efficient is the automated dideoxy method that sequences up to 1100 nucleotides in length, with a throughput of up to 19,000 bases per hour, can be sequenced with $98 \%$ accuracy. After a decade of work and a cost of about $\$ 500$ million, preliminary sequence information for the entire human genome of 3.0 billion base pairs was announced early in 2001 and complete information was released in 2003 . More recently, the genome sequencing of individuals, including that of James Watson, one of the discoverers of the double helix, has been accomplished. The sequencing price per genome is dropping rapidly and is currently less than $\$ 1,000$, meaning that the routine sequencing of individuals is within reach.


Remarkably, our genome appears to contain only about 21,000 genes, less than one-fourth the previously predicted number and only about twice the number found in the common roundworm. It's also interesting to note that the number of genes in a human $(21,000)$ is much smaller than the number of kinds of proteins (perhaps 500,000). This discrepancy arises because most proteins are modified in various ways after translation (posttranslational modifications), so a single gene can ultimately give many different proteins.


CUU-AUG-GCU-UGG-CCC-UAA - 28.7 DNA Synthesis

The ongoing revolution in molecular biology has brought with it an increased demand for the efficient chemical synthesis of short DNA segments, called oligonucleotides, or simply oligos. The problems of DNA synthesis are similar to those of peptide synthesis (Section 26.7) but are more difficult because of the complexity of the nucleotide monomers. Each nucleotide has multiple reactive sites that must be selectively protected and deprotected at specific times, and coupling of the four nucleotides must be carried out in the proper sequence. Automated DNA synthesizers are available, however, that allow the fast and reliable synthesis of DNA segments up to 200 nucleotides in length.


DNA synthesizers operate on a principle similar to that of the Merrifield solid-phase peptide synthesizer (Section 26.8). In essence, a protected nucleotide is covalently bonded to a solid support, and one nucleotide at a time is added to the growing chain by the use of a coupling reagent. After the final nucleotide has been added, all the protecting groups are removed and the synthetic DNA is cleaved from the solid support. Five steps are needed: