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AS Level Biology 9700

6. Nucleic acids and protein synthesis

Written by: Rhia Sakthivel
Formatted by: Pranav I

Index

6.1 The molecule of life
6.2 The structure of DNA and RNA
6.3 DNA replication 
6.4 The genetic code
6.5 Protein synthesis
6.6 Gene mutations

6.1 The molecule of life

  • The genetic material in living things must have:
    • The ability to store information → set of instructions to control cell behavior
    • The ability to copy itself accurately → no information can be lost

6.2 The structure of DNA and RNA

  • Nucleic acids are macromolecules
    • Nucleic acid is a polymer formed of many repeating nucleotide monomers
  • There are 2 types of nucleic acids:
    • DNA (double stand) → deoxyribonucleic acids
    • RNA (single stand) → ribonucleic acids

Nucleotide structure

Fig 6.1 The general structure of a nucleotide

Nitrogenous bases

  • 4 bases found in DNA
    • Adenine (A)
    • Guanine (G)
    • Thymine (T)
    • Cytosine (C)
  • In RNA, instead of thymine, we have uracil (U)
  • Adenine and guanine are purines with a double-ring structure
  • Cytosine, thymine, and uracil are pyrimidines with a single-ring structure

Pentose sugar

  • Pentose sugar has 5 carbon atoms
  • The pentose sugar determines the type of nucleotide
    • Ribose sugar → ribonucleotide
    • Deoxyribose sugar → deoxyribonucleotide
  • The difference is that deoxyribose has one less oxygen atom in the molecule

Phosphate group

  • Makes the nucleic acid molecule acidic in nature

ATP structure

  • Adenosine triphosphate (ATP) is NOT a part of DNA or RNA
  • However, it is a nucleotide

\[
\text{Adenine} + \text{Ribose} \rightarrow \text{Adenosine}
\]

\[
\text{Adenosine} + \text{Phosphate group (P)} \rightarrow \text{Adenosine monophosphate (AMP)}
\]

\[
\text{Adenosine monophosphate (AMP)} + \text{2 Phosphate groups (2P)} \rightarrow \text{Adenosine triphosphate (ATP)}
\]

  • Role of ATP:
    • Provide energy for the cell
    • E.g. active transport, endocytosis, exocytosis

Structure of a DNA molecule

  • One DNA molecule consists of two polynucleotide chains
  • The bases in one chain are attracted to the bases of the other chain by hydrogen bonding between the bases
    • This holds the chains together.
  • The two chains coil around each other to form a double helix
  • The strands run in opposite directions → antiparallel
  • Each strand has a sugar-phosphate backbone with phosphodiester bonds 
  • A = T and G ≡ C → complementary base pairing, meaning the 2 strands are complementary as well
    • A links with T by two hydrogen bonds; G links with C by three hydrogen bonds
  • A purine always pairs with a pyrimidine
    • The distance between the two backbones is therefore constant and always three rings wide
  • A complete turn of the double helix takes place every 10 base pairs
Fig 6.2 The structure of a DNA molecule

Store of information

  • The information is the sequence of bases → represented by the four letters, A, G, T, and C
  • Any sequence is possible within one strand, but the other strand MUST be complementary
  • The sequence acts as a coded message

Structure of an RNA molecule

  • RNA is a single polynucleotide strand
  • Three types of RNA are involved in protein synthesis:
    • Messenger RNA (mRNA)
    • Transfer RNA (tRNA)
    • Ribosomal RNA (rRNA)
  • tRNA and rRNA fold into complex structures, while mRNA remains as an unfolded strand

6.3 DNA replication

  • Multiple enzymes control replication (you have to know 2 in depth)
  • Step 1: unzipping
    • DNA helicase enzyme separates the two strands of DNA by the breaking of hydrogen bonds

DNA polymerase

  • DNA polymerase is used for the copying process
  • DNA polymerase attaches to EACH of the single strands
  • It adds one new nucleotide at a time → held by hydrogen bonding to the strand being copied
  • DNA polymerase can only copy in the 5′ to 3′ direction along each strand

Leading strand

  • One of the original strands is being copied in the same direction as the unwinding process
  • The DNA polymerase simply follows the unwinding process, copying the DNA

Lagging strand

  • However, in the other strand, the 5′ to 3′ direction of copying is in the opposite direction to the unwinding
  • The DNA polymerase has to copy an unwound piece of DNA and then go back and copy the next piece of unwound DNA
  • This creates short fragments of copied DNA called Okazaki fragments
Fig 6.3 The copying process with DNA polymerase

DNA ligase

  • DNA ligase connects neighboring nucleotides with phosphodiester bonds to form the sugar-phosphate backbone of the new strand
  • Finishes the lagging strand by connecting all the Okazaki fragments

Semi-conservative replication

  • This method of copying DNA is called semi-conservative replication
  • Each new DNA molecule retains half of the original molecule
    • 1 DNA molecule = 1 original strand + 1 newly replicated strand

🚨 DNA polymerase synthesizes new DNA strands, while DNA ligase joins DNA fragments together

6.4 The genetic code

  • The sequence of bases in the DNA of a cell is the code for all the proteins of that cell and organism.
  • Gene: a sequence of nucleotides that code for a polypeptide
  • There are 20 common amino acids found in proteins, and four different bases in DNA to code for them
  • The code for each amino acid is a triplet code → consists of three bases 
    • There are 64 different possibilities for a triplet code

Features of DNA genetic code

  • The code is universal
    • This means that each triplet codes for the same amino acid in all living things.
  • The code has punctuations
    • Three of the DNA triplets act as ‘full stops’ in the message
    • During protein synthesis, these stop triplets mark the end of a gene.
    • Some triplets can act as ‘start signals’, where the process of copying a gene starts
  • The code is described as redundant or degenerate
    • Some amino acids are coded for by more than one triplet (e.g. ACA & ACG both codes for cysteine)

6.5 Protein synthesis

  • DNA is found in the nucleus and proteins are made in ribosomes in the cytoplasm
  • mRNA acts as an intermediate molecule to carry information from the nucleus to ribosomes
  • “DNA makes RNA and RNA makes protein”
    • Transcription → DNA makes mRNA
    • Translation → mRNA is decoded to make protein

Transcription

  • Takes place in the nucleus where DNA is located
  • RNA polymerase is responsible for transcription
  • RNA polymerase attaches to the gene’s start point
  • DNA is unwound and hydrogen bonds between strands are broken, unzipping the DNA.
  • Two single strands are exposed:
    • Template strand (transcribed strand): used for RNA synthesis (complementary to RNA)
    • Non-transcribed strand: not copied
  • A complementary RNA copy of the template strand is made
  • RNA contains the base uracil instead of thymine
  • The DNA strand will contain START and STOP triplet codes to instruct what part of the DNA needs to be transcribed
Fig 6.3 Transcription of the DNA template strand

mRNA synthesis

  • mRNA is made from free nucleotides in the nucleus
  • RNA polymerase
    • Moves along the gene, pairing nucleotides with complementary DNA bases via hydrogen bonding
    • Joins adjacent nucleotides using phosphodiester bonds
  • Once a section is copied, hydrogen bonds between mRNA and DNA break
  • Transcription ends when a STOP triplet code is reached, releasing the completed mRNA
    • Leaves the nucleus through a nuclear pore in the nuclear envelope

Translation

  • mRNA is a complementary copy of the gene coding for the polypeptide
    • Triplet: DNA set of three bases coding for an amino acid
    • Codon: complementary set of three mRNA bases coding for an amino acid
  • Ribosomes facilitate translation and are composed of rRNA and protein, with small and large subunits
  • tRNA transfers amino acids to ribosomes for polypeptide synthesis
    • One end of tRNA carries a specific amino acid, and the other has an anticodon (three bases complementary to the mRNA codon)
    • Enzymes ensure each tRNA carries the correct amino acid
Fig 6.4 A tRNA molecule
  • Translation involves interactions between mRNA, tRNA, ribosomes, and enzymes
  • mRNA enters a groove between ribosome subunits, positioning itself to receive tRNA
  • First tRNA with an anticodon complementary to the first mRNA codon binds via hydrogen bonding
  • Ribosomes can accommodate two tRNAs at a time
    • The second tRNA anticodon binds to the next mRNA codon
  • Amino acids on adjacent tRNAs form a peptide bond
  • First tRNA exits, ribosome shifts one codon, and the next tRNA enters with a new amino acid
  • This repeats until a STOP codon (a codon that terminates translation) is reached
  • Completed polypeptide detaches, and folds into secondary and tertiary structures
    • Folding is aided by specialized proteins
    • Polypeptide may enter the ER for transport within the cell

6.6 Gene mutations

  • Gene mutation: a change in the nucleotide sequence of a DNA molecule causing altered mRNA, and a change in the primary structure of proteins
  • Chromosome mutation: a random and unpredictable change in the structure or number of chromosomes in a cell
  • Mutations occur due to:
    • Errors during DNA replication (copying errors)
    • DNA damage from factors like radiation and other mutagens
  • A change in the DNA base sequence may alter the amino acid sequence of the polypeptide it codes for
  • Gene mutations are random events and are typically harmful because:
    • They may disrupt the polypeptide’s amino acid sequence (primary structure)
    • This can alter how the polypeptide folds, changing its tertiary structure and effectiveness
    • Mutations in certain genes can lead to cancers

Types of mutations

  • Three of the most common gene mutations are:
    • Substitution → a base is replaced by a different base
    • Deletion → a base is lost and not replaced
    • Insertion → a base is added

Substitution

  • A substitution mutation occurs when one base in the DNA sequence is replaced by another
  • Substitution may or may not affect the amino acid sequence coded by the DNA
    • Example of substitution causing a change
      • Normal sequence: CAA|TTT|GAA|CCC → valine | lysine | leucine | glycine
      • Substituted sequence: CAA|TAT|GAA|CCC → valine | isoleucine | leucine | glycine
      • Result: Lysine is replaced by isoleucine
    • Example of substitution causing no change
      • Normal sequence: CAA|TTT|GAA|CCC → valine | lysine | leucine | glycine
      • Substituted sequence: CAA|TTC|GAA|CCC → valine | lysine | leucine | glycine
      • Result: No change in the amino acid sequence because both TTT and TTC code for lysine
  • The genetic code is degenerate, meaning multiple triplets can code for the same amino acid

Deletion and insertion

  • Deletions and insertions are much more likely to be serious than substitutions because they cause frame-shift mutations
  • Frame-shift mutations: is a gene mutation caused by the insertion or deletion of nucleotides, which shifts how the genetic code is read, leading to incorrect grouping of triplets
  • This shifts the reading frame, altering all triplets (codons) from the mutation point onward
  • The resulting sequence codes for incorrect amino acids, making the protein or polypeptide likely non-functional
  • For example:
    • Normal sequence: TAG|TAG|TAG|TAG|TAG|TAG|TAG|TAG|TAG|TAG|TAG
    • Insertion of a base (e.g. C): TAG|TAG|TAG|TAG|CTA|GTA|GTA|GTA|GTA|GTA|GTA
    • Deletion of a base: TAG|TAG|TAG|TAG|AGT|AGT|AGT|AGT|AGT|AGT
  • Both mutations cause the rest of the sequence to be altered, affecting the entire protein structure and function
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