Gc Cg

In eukaryotic cells, methylation is often related to gene expression. Sequences that are methylated typically show low levels of transcription while sequences lacking methylation are actively being transcribed (see Chapter 16). Methylation can also affect the three-dimensional structure of the DNA molecule.

Concepts]"

Methyl groups may be added to certain bases in DNA, depending on their positions in the molecule. Both prokaryotic and eukaryotic DNA can be methylated. In eukaryotes, cytosine bases are most often methylated to form 5-methylcytosine, and methylation is often related to gene expression.

www.whfreeman.com/pierce The latest on DNA methylation, at the Web site of the DNA Methylation Society

Bends in DNA

Some specific base sequences—such as a series of four or more adenine - thymine base pairs — cause the DNA double helix to bend. Bending affects how the DNA binds to certain proteins and may be important in controlling the transcription of some genes.

The DNA helix can also be made to bend by the binding of proteins to specific DNA sequences ( FIGURE 10.19). The SRY protein, which is encoded by a Y-linked gene and is responsible for sex determination in mammals (see Chapter 4), binds to certain DNA sequences (along the minor groove) and activates nearby genes that encode male traits. When the SRY protein grips the DNA, it bends the molecule about 80 degrees. This distortion of the DNA helix apparently facilitates the binding of other proteins that activate the transcription of genes that encode male characteristics.

10.19 The DNA helix can be bent by the binding of proteins to the DNA molecule.

Connecting Concepts Across Chapters]

This chapter has shifted the focus of our study to molecular genetics. The first nine chapters of this book examined various aspects of transmission genetics. In these chapters, the focus was on the individual: which phenotype was produced by an individual genotype, how the genes of an individual were transmitted to the next generation, and what types of offspring were produced when two individuals were crossed. In molecular genetics, our focus now shifts to genes: how they are encoded in DNA, how they are replicated, and how they are expressed.

Much of what follows in this book will depend on your knowledge of DNA. An understanding of all the major processes of information transfer — replication, transcription, and translation — requires an understanding of nucleic acid structure; discussions of recombinant DNA, mutation, gene expression, cancer genetics, and even population genetics are based on the assumption that you understand the basic structure and function of DNA. Thus the information in this chapter provides a critical foundation for much of the remainder of the book.

In this chapter, the history of how DNA's structure and function were unraveled has been strongly emphasized, because the DNA story illustrates how pivotal scientific discoveries are often made. No one scientist discovered the structure of DNA; rather, numerous persons, over a long period of time, made important contributions to our understanding of its structure. Watson and Crick's proposal for DNA's double-helical structure stands out as a singularly important contribution, because it combined many known facts about the structure into a new model that allowed important inferences about the fundamental nature of genes. The DNA story also illustrates the important lesson that science is a human enterprise, influenced by personalities, relations, and motivation.

CONCEPTS SUMMARY]_

• Genetic material must contain complex information, be replicated accurately, and have the capacity to be translated into the phenotype.

• Evidence that DNA is the source of genetic information came from the finding by Avery, MacLeod, and McCarty that transformation — the genetic alteration of bacteria—was dependent on DNA and from the demonstration by Hershey and Chase that viral DNA is passed on to progeny phages. The results of experiments with tobacco mosaic virus showed that RNA carries genetic information in some viruses.

• James Watson and Francis Crick proposed a new model for the three-dimensional structure of DNA in 1953.

• A DNA nucleotide consists of a deoxyribose sugar, a phosphate group, and a nitrogenous base. RNA consists of a ribose sugar, a phosphate group, and a nitrogenous base.

• The bases of a DNA nucleotide are of two types: purines (adenine and guanine) and pyrimidines (cytosine and thymine). RNA contains the pyrimidine uracil instead of thymine.

• Nucleotides are joined by phosphodiester linkages in a polynucleotide strand. Each polynucleotide strand has a 5' end with a phosphate and a 3' end with a hydroxyl group.

• DNA consists of two nucleotide strands that wind around each other to form a double helix. The sugars and phosphates lie on the outside of the helix, and the bases are stacked in the interior. Bases from the two strands are joined by hydrogen bonding. The two strands are antiparallel and complementary.

DNA molecules can form a number of different secondary structures, depending on the conditions in which the DNA is placed and on its base sequence. B-DNA, which consists of a right-handed helix with approximately 10 bases per turn, is the most common form of DNA in cells.

The structure of DNA has several important genetic implications. Genetic information resides in the base sequence of DNA, which ultimately specifies the amino acid sequence of proteins. Complementarity of the bases on DNA's two strands allows genetic information to be replicated.

Important pathways by which information passes from DNA to other molecules include: (1) replication, in which one molecule of DNA serves as a template for the synthesis of two new DNA molecules; (2) transcription, in which DNA

serves as a template for the synthesis of an RNA molecule; and (3) translation, in which RNA codes for protein.

The central dogma of molecular biology proposes that information flows in a one-way direction, from DNA to RNA to protein. Clear exceptions to the central dogma are not known.

Pairing between bases on the same nucleotide strand can lead to hairpins and other secondary structures. Inverted repeats are sequences on the same strand that are inverted and complementary; they can lead to cruciform structures. DNA methylation is the addition of methyl groups to the nucleotide bases. In bacteria, adenine and cytosine are commonly methylated. Among eukaryotes, cytosine bases are most commonly methylated to form 5-methylcytosine. Some sequences, such as a series of four or more adenine - thymine base pairs, can cause DNA to bend, which may affect gene expression.

(important terms nucleotide (p. 000) Chargaff's rules (p. 000) transforming principle (p. 000) isotopes (p. 000) X-ray diffraction (p. 000) ribose (p. 000) deoxyribose (p. 000) nitrogenous base (p. 000) purine (p. 000) pyrimidine (p. 000) adenine (A) (p. 000)

guanine (G) (p. 000) cytosine (C) (p. 000) thymine (t) (p. 000) uracil (U) (p. 000) nucleoside (p. 000) phosphate group (p. 000) deoxyribonucleotide (p. 000) ribonucleotide (p. 000) phosphodiester linkage (p. 000) polynucleotide strand (p. 000) 5' end (p. 000)

3' end (p. 000) antiparallel (p. 000) complementary (p. 000) B-DNA (p. 000) A-DNA (p. 000) Z-DNA (p. 000) local variation (p. 000) transcription (p. 000) translation (p. 000) replication (p. 000) central dogma (p. 000)

reverse transcription (p. 000) RNA replication (p. 000) hairpin (p. 000) inverted repeats (p. 000) palindrome (p. 000) cruciform (p. 000) DNA methylation (p. 000) 5-methylcytosine (p. 000)

Worked Problems

1. The percentage of cytosine in a double-stranded DNA molecule is 40%. What is the percentage of thymine?

In double-stranded DNA, A pairs with T, whereas G pairs with C; so the percentage of A equals the percentage of T, and the percentage of G equals the percentage of C. If C = 40%, then G also must be 40%. The total percentage of C + G is therefore 40% + 40% = 80%. All the remaining bases must be either A or T; so the total percentage of A + T = 100% - 80% = 20%; because the percentage of A equals the percentage of T, the percentage of T is 20%/2 = 10%.

2. Which of the following relations will be true for the percentage of bases in double-stranded DNA?

An easy way to determine whether the relations are true is to arbitrarily assign percentages to the bases, remembering that, in double-stranded DNA, A = T and G = C. For example, if the percentages of A and T are each 30%, then the percentages of G and C are each 20%. We can substitute these values into the equations to see if the relations are true.

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