Chapter 13: The Molecular Basis of Inheritance – DNA Structure, Replication, and Genetic Material

Chapter 13: The Molecular Basis of Inheritance

Key Terms

• Antiparallel

• Chargaff's rule

• Chromatin

• Chromosome

• Complementary

• DNA ligase

• DNA polymerase

• DNA template

• Double helix

• Elongation

• Euchromatin

• Helicase

• Heterochromatin

• Histones

• Lagging strand

• Leading strand

• Mismatch repair

• Nuclease

• Nucleoid

• Nucleosome

• Nucleotide excision repair

• Okazaki fragment

• Origin of replication

• Primase

• Primer

• Purine

• Pyrimidine

• Replication

• Replication fork

• RNA

• Rosalind Franklin

• Semiconservative replication

• Single-strand DNA binding proteins

• Telomere

• Telomerase

• Topoisomerase

• Watson and Crick

DNA as the Genetic Material

Historical Context and Scientific Inquiry

The identification of the molecules responsible for inheritance was a major challenge in early 20th-century biology. Genes were found to be located on chromosomes, which are composed of DNA and protein. Initially, proteins were considered stronger candidates for genetic material, but studies of bacteria and viruses shifted focus to DNA.

• T. H. Morgan's group established genes are on chromosomes.

• DNA and protein were both considered possible genetic materials.

• Role of DNA in heredity was elucidated through experiments with bacteria and viruses.

Evidence That DNA Can Transform Bacteria

Frederick Griffith's experiments in 1928 demonstrated that genetic traits could be transferred between bacterial strains, leading to the concept of transformation.

• Griffith used two strains of Streptococcus pneumoniae: one pathogenic (S) and one harmless (R).

• Mixing heat-killed pathogenic S strain with living R strain resulted in some R cells becoming pathogenic.

• Transformation: Change in genotype and phenotype due to assimilation of foreign DNA.

• Oswald Avery and colleagues later identified DNA as the transforming substance.

Evidence That Viral DNA Can Program Cells

Further evidence for DNA as genetic material came from studies of bacteriophages (phages), viruses that infect bacteria.

• Bacteriophage: Virus composed of DNA (or RNA) enclosed in a protein coat.

• Viruses must infect cells and use their metabolic machinery to reproduce.

• Hershey and Chase (1952) showed that only DNA, not protein, enters E. coli during phage infection, confirming DNA as the genetic material.

Chargaff's Rules and DNA Diversity

Erwin Chargaff discovered that DNA composition varies between species and established two key rules:

• The base composition of DNA varies between species.

• In any species, the percentage of adenine (A) equals thymine (T), and guanine (G) equals cytosine (C).

Structure of DNA

Building the Structural Model

Multiple researchers contributed to the discovery of DNA's structure. Maurice Wilkins and Rosalind Franklin used X-ray crystallography to study DNA, producing images that enabled Watson and Crick to deduce its double helical structure.

• Franklin's X-ray images revealed DNA is helical and consists of two strands.

• Watson and Crick built models showing two sugar-phosphate backbones with nitrogenous bases paired inside.

• The backbones are antiparallel (run in opposite directions).

Base Pairing and the Double Helix

Watson and Crick determined that base pairing is specific:

• Adenine (A) pairs only with Thymine (T).

• Guanine (G) pairs only with Cytosine (C).

• Pairing a purine (A or G) with a pyrimidine (T or C) results in a uniform width, consistent with X-ray data.

• Nitrogenous base pairs are held together by hydrogen bonds.

Chargaff's rules are explained by this base pairing: amount of A = T, and G = C.

DNA Replication and Repair

Base Pairing to a Template Strand

DNA replication relies on the complementary nature of the two strands. Each strand serves as a template for the synthesis of a new strand.

• Parent DNA unwinds; daughter strands are built using base-pairing rules.

Models of DNA Replication

• Semiconservative model: Each daughter DNA molecule has one old (parental) strand and one newly synthesized strand.

• Conservative model: Parental strands rejoin; daughter molecule is entirely new.

• Dispersive model: Each strand is a mix of old and new DNA.

Mechanism of DNA Replication

DNA replication is rapid and accurate, involving many enzymes and proteins. The process is similar in prokaryotes and eukaryotes.

• Replication begins at origins of replication, forming replication bubbles.

• At each bubble end is a replication fork, where DNA is unwound.

• Multiple replication bubbles in eukaryotes speed up DNA copying.

Proteins Involved in DNA Replication

• Helicases: Untwist the double helix at replication forks.

• Single-strand binding proteins: Stabilize single-stranded DNA.

• Topoisomerase: Relieves strain ahead of the replication fork by breaking, swiveling, and rejoining DNA strands.

Summary Table: Key Proteins in DNA Replication

Protein/Enzyme	Function
Helicase	Unwinds DNA at replication fork
Single-strand binding protein	Stabilizes unwound DNA
Topoisomerase	Relieves supercoiling ahead of fork
Primase	Synthesizes RNA primer
DNA polymerase	Adds nucleotides to growing DNA strand
DNA ligase	Joins Okazaki fragments

Example: DNA Replication in E. coli

Replication starts at a single origin, forming a bubble and two forks. Daughter DNA molecules are synthesized as the forks move outward.

Additional info:

• DNA replication is semiconservative, ensuring genetic continuity.

• Errors are rare due to proofreading and repair mechanisms.