The Genetic Material Must Exhibit Four Characteristics

• For a molecule to serve as the genetic material, it must be able to replicate, store information, express information, and allow variation by mutation.

• The central dogma of molecular genetics is that DNA makes RNA, which makes proteins (Figure 10.1).

• The genetic material is physically transmitted from parent to offspring. Proteins and nucleic acids were the major candidates for the genetic material.

• For a long time, protein was favored to be the genetic material. It is abundant in cells, it was the subject of the most active areas of genetic research, and DNA was thought to be too simple to be the genetic material, with only four types of nucleotides as compared to the 20 different amino acids of proteins.

• Griffith showed that avirulent strains of Diplococcus pneumoniae could be transformed to virulence (Figure 10.3). He speculated that the transforming principle could be part of the polysaccharide capsule or some compound required for capsule synthesis.

• Avery, MacLeod, and McCarty demonstrated that the transforming principle was DNA and not protein (Figure 10.4).

• Nucleotides are the building blocks of DNA. They consist of a nitrogenous base, a pentose sugar, and a phosphate group.

• The nitrogenous bases can be purines or pyrimidines. The purines are adenine (A) and guanine (G). The pyrimidines are cytosine (C), thymine (T), and uracil (U) (Figure 10.9).

• DNA and RNA both contain A, C, and G, but only DNA contains T and only RNA contains U.

• RNA contains ribose as its sugar; DNA contains deoxyribose (Figure 10.9).

• A nucleoside contains the nitrogenous base and the pentose sugar. A nucleotide is a nucleoside with a phosphate group added (Figure 10.10).

• Nucleotides are linked by a phosphodiester bond between the phosphate group at the C-5' position and the OH group on the C-3' position (Figure 10.12).

• Chargaff showed that the amount of A is proportional to T and the amount of C is proportional to G, but the percentage of C + G does not necessarily equal the percentage of A + T (Table 10.3).

• X-ray diffraction of DNA showed a 3.4 angstrom periodicity, characteristic of a helical structure (Figure 10.13).

• Watson and Crick proposed DNA is a right-handed double helix in which the two strands are antiparallel and the bases are stacked on one another. The two strands are connected by A-T and G-C base pairing and there are 10 base pairs per helix turn (Figure 10.14).

• The A-T and G-C base pairing provides complementarity of the two strands and chemical stability to the helix.

• A-T base pairs form two hydrogen bonds and G-C base pairs form three hydrogen bonds (Figure 10.16).

Viral and Bacterial Chromosomes Are Relatively Simple DNA Molecules

• Bacterial and viral chromosomes are usually a single nucleic acid molecule, are largely devoid of associated proteins, and are much smaller than eukaryotic chromosomes.

• Bacterial chromosomes are double-stranded DNA and are compacted into a nucleoid.

• DNA in bacteria may be associated with HU and H DNA-binding proteins.

Supercoiling Is Common in the DNA of Viral and Bacterial Chromosomes

• Supercoiling compacts DNA (Figure 12.4). Most closed circular DNA molecules in bacteria are slightly underwound and supercoiled.

• Topoisomerases cut one or both DNA strands and wind or unwind the helix before resealing the ends.

DNA Is Organized into Chromatin in Eukaryotes

• Eukaryotic chromosomes are complexed into a nucleoprotein structure called chromatin.

• Chromatin is bound up in nucleosomes with histones H2A, H2B, H3, and H4.

• Nucleosomes are condensed several times to form the intact chromatids (Figure 12.9).

• Chromatin remodeling must occur to allow the DNA to be accessed by DNA binding proteins.

• Euchromatin is uncoiled and active, whereas heterochromatin remains condensed and is inactive.

Chromosome Banding Differentiates Regions along the Mitotic Chromosome

• Mitotic chromosomes have a characteristic banding pattern. In C-banding, only the centromeres are stained (Figure 12.11). G-banding is due to differential staining along the length of each chromosome (Figure 12.12).

• The differential staining reactions reflect the heterogeneity and complexity of the chromosome.

Eukaryotic Chromosomes Demonstrate Complex Organization Characterized by Repetitive DNA

• Repetitive DNA sequences are repeated many times within eukaryotic chromosomes, and there are a number of categories of repetitive DNA (Figure 12.14).

• Satellite DNA is highly repetitive and consists of short repeated sequences..

• Centromeres are the primary constrictions along eukaryotic chromosomes and mediate chromosomal migration during mitosis and meiosis.

• There are two types of telomere sequences: telomeric DNA sequences and telomere-associated sequences. Both consist of repetitive sequences.

• Moderately repetitive DNA includes variable number tandem repeats (VNTRs), minisatellites, and microsatellites.

• Short interspersed elements (SINES), long interspersed elements (LINES), and transposable sequences are repetitive DNAs that are dispersed throughout the genome rather than tandemly repeated.

The Vast Majority of a Eukaryotic Genome Does Not Encode Functional Genes

• Highly repetitive and moderately repetitive DNA constitute up to 40% of the human genome. There are also a large number of single-copy noncoding regions, some of which are pseudogenes.