The Molecular Basis of Heredity: Structure and Function of Genetic Material

The Molecular Basis of Heredity, Variation, and Evolution

Criteria for Genetic Material

The genetic material of a cell must fulfill several essential criteria to ensure proper inheritance and function:

• Information: Must contain all instructions necessary to build and maintain an organism.

• Transmission: Must be reliably passed from parent to offspring.

• Replication: Must be capable of accurate copying for inheritance.

• Variation: Must allow for changes to account for phenotypic diversity within species.

Historical Determination of Genetic Material

For many years, the identity of the genetic material was unknown. Candidates included lipids, carbohydrates, proteins, and nucleic acids. By the early 1900s, inheritance was linked to chromosomes, which are composed of DNA and protein. Classic experiments established DNA as the genetic material.

Transmission Genetics: Classic Experiments

Griffith's Transformation Experiment

Frederick Griffith studied Streptococcus pneumoniae and discovered transformation, a process where genetic material from dead cells could change the phenotype of living cells.

• R strain: No capsule, rough colonies, not protected from immune system.

• S strain: Capsule, smooth colonies, protected from immune system.

• Key finding: Something from heat-killed S cells transformed R cells into S cells.

Avery, MacLeod, and McCarty Experiment

These scientists fractionated S strain cells into macromolecules and found that only DNA could transform R cells into S cells, confirming DNA as the genetic material.

• DNA extract: Transformed R cells.

• DNase treatment: Prevented transformation, confirming DNA's role.

Hershey and Chase Experiment

Studied bacteriophage T2, composed of DNA and protein, to determine which component was the genetic material. Radioactive labeling with 32P (DNA) and 35S (protein) showed that DNA entered the bacterial cell during infection.

• Result: Most 32P remained with cells, most 35S was found in the supernatant.

• Conclusion: DNA is the genetic material injected into cells.

RNA as Genetic Material in Some Viruses

In 1956, Gierer and Schramm showed that RNA from tobacco mosaic virus (TMV) could cause infection, establishing RNA as the genetic material in some viruses. Many viruses with RNA genomes have since been discovered.

Structure of Nucleic Acids

Levels of Nucleic Acid Structure

DNA and RNA are large macromolecules with several levels of structural complexity:

• Nucleotides: The monomeric units.

• Strand: Nucleotides linked together.

• Double Helix: Two DNA strands interact.

• Chromosome: 3D folding and interaction with proteins.

Nucleotide Structure

Nucleotides are composed of a phosphate group, a pentose sugar (deoxyribose in DNA, ribose in RNA), and a nitrogenous base (purine or pyrimidine).

• Purines: Adenine (A), Guanine (G) – double ring structure.

• Pyrimidines: Cytosine (C), Thymine (T, in DNA), Uracil (U, in RNA) – single ring structure.

Nucleosides and Nucleotides

A nucleoside consists of a base and a sugar. A nucleotide is a nucleoside with one or more phosphate groups.

• Adenosine: Adenine + ribose.

• Deoxyadenosine: Adenine + deoxyribose.

• AMP, ADP, ATP: Adenosine mono-, di-, and triphosphate.

Formation of Nucleic Acid Strands

Nucleotides are covalently linked by phosphodiester bonds, connecting the 5' carbon of one nucleotide to the 3' carbon of another. This gives the strand directionality (5' to 3').

Discovery and Structure of DNA

Scientific Framework for DNA Structure

Many scientists contributed to the discovery of DNA's structure:

• Linus Pauling: Proposed alpha-helical structure.

• Rosalind Franklin & Maurice Wilkins: Provided x-ray diffraction data.

• Erwin Chargaff: Described base pairing rules (A=T, G=C).

• Watson & Crick: Compiled data into the double helix model.

Chargaff's Rules

Chargaff found that the amount of adenine equals thymine, and guanine equals cytosine in DNA, supporting the base pairing model.

Watson and Crick Model of DNA

DNA consists of two polynucleotide strands held together by hydrogen bonds between bases:

• A-T: 2 hydrogen bonds.

• G-C: 3 hydrogen bonds.

• Bases: Located on the interior, stacked like plates.

• Sugar-phosphate backbone: On the exterior.

Key Features of DNA Double Helix

• Antiparallel strands: One runs 5' to 3', the other 3' to 5'.

• Right-handed helix: Spirals clockwise.

• 10 bases per turn: Each complete twist is 3.4 nm.

Major and Minor Grooves

DNA has two asymmetrical grooves on its surface: the major and minor grooves. Proteins often bind to the major groove, which can be sequence-specific.

Alternative DNA Structures

DNA can adopt different secondary structures:

• B-DNA: Predominant form in cells.

• A-DNA: Found in vitro under low humidity, 11 bp per turn.

• Z-DNA: Left-handed helix, favored by GG-rich sequences and high salt; may play roles in transcription and recombination.

Triplex DNA

Triplex DNA can form when a synthetic strand binds to the major groove of double-stranded DNA. This structure is sequence-specific and can affect replication, transcription, and recombination.

RNA Structure

Primary and Secondary Structure of RNA

RNA is usually single-stranded but can form short double-stranded regions through complementary base pairing (A-U, C-G). RNA double helices are right-handed and typically have the A form with 11-12 base pairs per turn.

• Secondary structures: Hairpins, bulge loops, internal loops, multibranched junctions.

• Factors influencing structure: Base pairing, base stacking, interactions with ions, small molecules, and proteins.

Transfer RNA (tRNA) Structure

tRNAs fold into a characteristic shape, carrying amino acids at the 3' end and exposing the anticodon region for interaction with mRNA during translation.

Summary Table: DNA vs. RNA

Feature	DNA	RNA
Sugar	Deoxyribose	Ribose
Base	A, T, G, C	A, U, G, C
Strandedness	Double-stranded	Single-stranded (usually)
Function	Genetic material	Protein synthesis, regulation, genetic material in some viruses

Additional info: The notes expand on brief points with academic context, definitions, and examples to ensure completeness and clarity for genetics students.