Information of Life

Nucleic Acids - The Key to Life

• Nucleic acids carry the genetic code that determines the order of amino acids in proteins
• Genetic material stores information, can be replicated, and undergoes mutations
• Differ from proteins as it has phosphorus and NO sulphur
• Made up of several chains of nucleotides
• DNA and RNA are types of nucleic acids

Nucleotide

• Sugar-phosphate backbone (ensures stability of the molecule)
  • Pentose sugar
    • Deoxyribose in DNA
    • Ribose in RNA
  • Phosphate group
• Organic bases
  • Purines (double rings of C and N - bigger)
    • Adenine
    • Guanine
  • Pyrimidines (single ring of C and N - smaller)
    • Thymine in DNA only
    • Uracil in RNA only
    • Cytosine

Deoxyribonucleic Acid (DNA)

• Made up of 2 separate chains of nucleotides hold together by base pairing
  • Connected by weak hydrogen bonds
  • Can easily be opened for replication
  • Adenine-Thymine has 2 H-bonds
  • Cytosine-Guanine has 3 H-bonds
• DNA normally twist into a helix (coil) / forms a double helix
  • Makes the molecule compact (store a lot in small space)
  • Protects from damage as base pairs are facing inwards
• Both chains of DNA are
  • Directional → according to the attachment between sugars and phosphate group
  • Antiparallel → essential for gene coding and replication

Semi-Conservative Replication of DNA

• Semi-conservative replication: each DNA strand acts as a template for the formation of a new strand
• Happens during interphase S of the cell cycle
• Unwinding
  • Enzyme DNA helicase separates 2 strands of DNA by breaking hydrogen bonds
  • Strands are separated a little at a time (not all at once!)
  • This creates a replication fork which moves along the strand
• Free DNA molecules join up to exposed bases by complementary base pairing
  • Adenine with Thymine (A=T 2-H bonding)
  • Cytosine with Guanine (CΞG 3-H bonding)
• For the new 5' to 3' strand
  • Enzyme DNA polymerase catalyses the joining of the separate nucleotides
  • New strand is completed "all in one go"
• For the 3' to 5' strand
  • DNA polymerase produces short sections of strand
  • These sections have to be joined by DNA ligase to make the completed new strand
  • Specific base pairing ensures that two identical copies of the original DNA have been formed

Ribonucleic Acid (RNA)

• Ribose instead of deoxyribose
• Single chain (shorter than DNA)
  • Can pass through nucleus into cytoplasm
• Base difference
  • Uracil instead of thymine
  • Adenine, guanine, and cytosine are the same
• Messenger RNA (mRNA) carries the code from DNA that will be translated into an amino acid sequence
• Transfer RNA (tRNA) transfers amino acids to their correct position on the mRNA strand

Genetic Code

• DNA codes for assembly of amino acids / forms a polypeptide chain (proteins - enzymes)
• The code is read in a sequence of three bases called
  • Triplets on DNA (e.g. CAC TCA)
  • Codons on mRNA (e.g. GUG AGU)
  • Anticodons on tRNA (e.g. CAC UCA) - must be complementary to the codon of mRNA
• Each triplet codes for one amino acid
• Single amino acid may have up to 6 different triplets for it due to the redundancy of the code / some amino acids are coded by more than one codon (degenerate code)
• Same triplet code will give the same amino acid in all organisms (universal code)
• We have 64 possible combinations of the 4 bases in triplets, 43
• No base of one triplet contributes to part of the code next to it (non-overlapping)
• Few triplets code for START and STOP sequences for polypeptide chain formation
  • START: AUG
  • STOP: UAA, UAG, UGA

DNA and Inheritance

• Cell metabolism: reactions inside cells
• Metabolic pathway: sequence of chemical reactions
• Alleles: different forms of the same gene
• Gene: length of DNA that carries the code for a protein (enzyme)
  • Enzyme effect the cell's metabolism
  • Visible changes are described with the phenotype
  • The phenotype is influenced by the metabolic pathway
• Therefore
  • DNA controls enzyme production
  • Enzymes control metabolic pathways
  • Metabolic pathways influence the phenotype of an organism

Alleles and Genes

• Humans have 46 chromosomes
  • 22 of them are paired up as homologous chromosomes
  • Females have an additional homologous pair of sex chromosomes (XX)
  • Males have an X and Y sex chromosome
• Pair of homologous chromosomes
  • One of the pair is inherited from the mother, one from the father
  • Gene is a small section of DNA that codes for a specific characteristic
    • Hair colour,
    • Eye colour, ...
  • Found on both pairs of chromosomes at the same locus (position)
  • A gene can have different alleles (forms)
    • Brown eyes, blue eyes, ...
    • Black hair, brown hair, ...
  • This influences the phenotype
• Multiple alleles
  • Human ABO blood group is controlled by the gene called immunoglobulin I
  • The immunoglobulin gene has 3 alleles IA, IB, I0
  • These alleles code for antigen A, B, neither A/B, respectively
  • Only 2 alleles can be present → IAIB is codominant, I0 is recessive

Genes Control Phenotype

Mutation

• Change in one or more nucleotide bases in the DNA
• Change in the genotype (may be inherited)
• Deletion: reading frame shifts
• Substitution: one base replaced by another
• Duplication: repetition of part of the sequence
• Addition: addition of extra base

Cystic Fibrosis

• Revision from Unit 1 Section 3.1.3(c)
• Autosomal recessive disorder
• Mutation of the CFTR gene on chromosome 7
• Deletion of 3 bases / allele is missing 3 nucleotides
• Those nucleotides code for the amino acid phenylalanine
• Phenylalanine is missing from the CFTR protein
• Faulty CFTR protein cannot control the opening of chloride channels in the cell membrane

Phenylketonuria (PKU)

• Autosomal recessive disorder
• Gene mutation in DNA/gene coding for the enzyme phenylalanine hydroxylase
• Phenylalanine hydroxylase is not produced
• Amino acid phenylalanine cannot be converted to the amino acid tyrosine
• Tyrosine
  • Necessary to produce the pigment melanin
  • Patients are fair-haired, fair skinned and blue eyed (phenotype)
• Phenylalanine
  • Accumulates in the blood and causes irreversible brain damage
  • Found in most food that contains proteins
  • Treated by avoiding food that contains phenylalanine (diet low in protein)
  • Levels in blood are regularly measured by GP
• All babies are screened shortly after birth to prevent learning difficulties

Normal:

Defect (PKU):