Molecular Biology: DNA Structure and Function

Molecular Genetics (BHS016-1)

• Course delivered by Dr Taiwo Shittu
• Course code: BHS016-1

Nucleic Acids (BHS016-1 Topic 1)

• Learning Outcomes:
  • Students should be able to recall the chemical structure and key components of nucleotides.
  • Explain the formation of nucleic acids from individual nucleotides.
  • Describe the 3D structure of DNA.
  • Understand the various functions of nucleic acids and nucleotides.

What Is Genetics?

• Genetics is the study of heredity.
• Heredity is controlled by genes.
• Genes are units of biological information.
• Genes are units of inheritance.

Why Is Genetics Important?

• Genetics plays a role in various fields:
  • Biomedical science (e.g., heart damage from faulty genes).
  • Biological science (e.g., extracting genetic information from ancient rhino teeth).
  • Forensic science (e.g., genetic evidence in unsolved rape cases).

Basic Structure Of The DNA Molecule (Page 6)

• This section likely describes the fundamental composition of the DNA molecule.

How To Identify Genetic Material? (Page 7)

• Genetic material was unknown prior to 1950s.
  • Genetic material must contain complex information.
  • Genetic material must replicate faithfully.
  • Genetic material must encode the phenotype.
• Definition: Phenotype

How Do We Know It Is DNA? (Page 8)

• Nucleic acids were discovered in the nucleus (1869).
• Histone proteins were discovered in the nucleus (1884).
• The nucleus was shown to carry genetic material (1887).
• Questions about the genetic material in chromatin (i.e., whether DNA or proteins).
• Tetranucleotide theory misled the conclusion (Levene 1910).
• Truth was realised in 1944 (Avery et al.).
• Definition: Chromatin

Timeline Of DNA As Genetic Code (Page 9)

• Presents a timeline of significant discoveries related to DNA's role as the genetic code.
  • Includes dates and researchers/experiments associated with key stages in DNA research.

How Do We Know It Is DNA? (Page 10)

• Avery et al. worked with two types of Streptococcus pneumoniae bacteria—S and R strains
• S strain: virulent (caused disease in mice).
• R strain : non-virulent (did not cause disease in mice).
• Heating and killing the S strain of bacteria meant they couldn't cause disease anymore
• Combining dead S strain with living R strain transformed living R strain into virulent S strain

1944 – Avery, Macleod, And McCarty (Page 12, 13)

• Experiment aimed at identifying the chemical nature of the transforming substance, which was found to be DNA
  • Different enzymes such as RNase, Protease, and DNase were used during different stages of the transformation process to determine chemical components responsible for the transformation.
• Conclusion: DNase alone destroyed the transformation substance, suggesting that DNA was the transforming substance.

How Can DNA Carry Information? (Page 14, 15, 16, 17, 18)

• 1800s—Kossel showed DNA contained four nitrogenous bases.
• Definition: Purine, Pyrimidine.

How Can DNA Carry Information? (Page 17)

• 1948 – Chargaff demonstrated DNA contained fixed ratios of nucleotides.
  • Different organisms had different ratios. -(A+G) = (T+C) for all DNA samples

How Can DNA Carry Information? (Page 19)

• 1953 – Watson and Crick discovered DNA is a double helix.
• Human chromosomes are linear, with two complementary and antiparallel strands forming a helical shape

Primary Structure of DNA (Pages 20, 21, 22, 23)

• Nucleotides join to form polymers by phosphodiester bonds.
  • Phosphodiester bond forms between the 5' phosphate group of one nucleotide to the 3' hydroxyl group of another nucleotide
• Covalent bonding of nucleotides produces a sugar-phosphate backbone
• Definition: Covalent, 5' prime, 3' prime.

Secondary Structure of DNA (Page 24, 25, 26)

• Chargaff's rules: base pairing
  • Bases pair by hydrogen bonding—A with T, G with C
    • Two H-bonds link A to T.
    • Three H-bonds link G to C.
  • Definition: H-bond.
  • Linear polynucleotide strands pair to form a double stranded molecule.
  • Complementary base pairing

Summary of Basic DNA Structure (Page 27)

• DNA consists of two polynucleotide strands
  • Each strand: sugar-phosphate backbone.
  • Nitrogenous bases on the inside.
  • Hydrogen bonds join bases of two strands.
  • A-T, G-C pairing.
  • Two polynucleotide strands are complementary and antiparallel.

How Can DNA Carry Information? (Page 28)

• Genetic material must contain complex information.
  • Extremely long sequences of nucleotide
• Genetic material must replicate faithfully.
  • Complementary base pairing means each strand serves as template for the production of a new strand.
• Genetic material must encode the phenotype.

Tertiary Structure of DNA (Page 29)

• This section likely deals with the 3D arrangement of a DNA molecule.

DNA is a Double Helix (Page 31)

• 5'-3' phosphodiester bonds cause torsional force that twists the double stranded DNA molecule.
• Forms an alpha helix
• DNA has two anti-parallel chains
  • Right-handed helix
  • Major and minor grooves

B-DNA Structure (Page 32)

• The DNA backbone is formed from deoxyribose sugars linked by phosphates.
• Key structural features include the major and minor grooves.
• Specific dimensions of the double helix are described (e.g., diameter, distance between base pairs).

DNA Requires Further Packing (Page 33)

• In cells: each double-stranded DNA molecule forms a structure called a chromosome.
• Bacterial chromosome (E. coli) is 4.6 million base pairs long (1000x longer than the bacterial cell)
• Human nuclei contain 3.2 billion base pairs (3230 Mbp) (14000 x longer than the nucleus)

Prokaryote DNA Simple Structure (Page 34)

• Prokaryotes (bacteria) typically have a single chromosome with a simple structure.
  • DNA is mostly folded into long loops, held in place by structural proteins.

Bacterial DNA Folded In Twisted Loops (Page 35)

• Visual representation of bacterial DNA folding and looping

Eukaryotic DNA Shows Complex Packing (Page 36)

• Eukaryotic DNA displays a more complex packing structure compared to prokaryotic DNA
• DNA packing involves several hierarchical levels, starting from the double helix to the chromosome.
  • Dimensions at each level of packing are shown

Double Helix Packed Into Nucleosomes (Page 37)

• 160-200 base pairs of DNA are wrapped around eight core histone proteins.
• Nucleosomes are linked together by linker histone, H1.

Nucleosomes Packed Into 30 nm Fibre (Page 38)

• Nucleosomes are further organized into a 30 nm fiber ("beads on a string").
• This section depicts the structure

30 nm Fibre Packed Into Larger Coils (Page 39)

• 30nm fiber further coils into larger structures like 300nm, then 700nm fibres
• Scaffold proteins are likely involved in the organization of these higher-order coils

700 nm Coiled Coil Forms Chromosome (Page 40)

• This describes further coiling of the 700nm filament into the structure of a chromosome.

Eukaryotic DNA Shows Complex Packing (Page 41)

• DNA is wound around histone proteins to form nucleosomes, which lead to a 30nm fiber
• Packing results in the 700nm coiled coil that forms a chromosome.

DNA Packing Alters During Cell Cycle (Pages 42, 43)

• During interphase: chromatin regions are loosely packed (euchromatin).
  • Transcriptionally active regions (codes for proteins & RNAs)
• During M-phase: chromatin is tightly packed (heterochromatin).
  • Includes centromeres & telomeres.

Functions of DNA and Nucleotides (Pages 44, 45, 46, 47, 48)

• DNA functions include:
  • Provide instructions for building proteins (e.g. genes).
  • Control protein expression using regulatory regions.
  • Includes non-coding DNA whose function is still unknown.
• Other DNA types (e.g. mitochondrial, chloroplast) and their specific functions are described.
• Nucleotide functions described
  • Cyclic Nucleotide Monophosphates (signaling molecules like cAMP)
  • Coenzymes
  • Nucleotide Triphosphates provide energy (e.g., ATP, GTP) and participate in enzymatic phosphorylation.

Summary (Page 49)

• Provides a summary of the key concepts presented in the lecture.

To-Do List (Page 50)

• Tasks for students to complete before the next lecture.
  • Review DNA structures.
  • Define key terms.
  • Draw diagrams and other illustrations.

Before Next Week's Lecture (Page 51)

• For next lecture: read relevant textbook pages for information on chromosome structure.