Chapter 19

• Mutation

  change in the sequence of bases in DNA
• Protein synthesis might be disrupted if mutation occurs within a gene 
• How are changes in sequence of bases in DNA caused

  • by substitution, insertion & deletion
• What is substitution?

  • when one nucleotide is swapped for another
• Substation having an effect on protein

  • Change of one nucleotide may change codon in which it is found which would change the primary structure of the protein 
• Substation having no effect on protein

  • Degenerate nature of genetic code may mean new codon still codes for same amino acid leading to no change in the protein synthesised 
• Effects of insertion and deletion

  • Leads to a frameshift mutations 
  • Genetic code is read in non-overlapping groups of 3 bases - each 3 bases corresponds to one specific amino acid 
  • Addition or deletion of a nucleotide moves or shifts the reading frame of the sequence of bases - this will change every successive codon from the point of mutation 
  • Biggest impact on cell 
• Effect of different point mutations on codons and sequence of codons

  
• What effect will changed protein primary structure have?

  • Position and involvement of R-group will determine the interactions/ chemical bonds it can form - this impacts upon the secondary & tertiary structure of the protein
  • E.g. if protein is in enzyme even smallest alteration in tertiary structure may mean substrate won't be able to bind to active site making it non-functional
• 3 effects of different mutation

  • no effect
  • damaging
  • beneficial
• No-effect mutations

  • no effect on phenotype as normal functioning proteins are still synthesised
  • known as silent or neutral mutations & sometimes conservative missense mutations (incorporation of a similar amino acid won't affect function)
• Damaging mutations

  • phenotype affected in negative way because proteins are no longer synthesised or proteins synthesised are non-functional
  • can interfere with essential processes
  • 2 types: nonsense mutations & non-conservative missense mutations
• Nonsense mutations 


  cause one codon to become a stop codon so protein produced is much shorter & therefore non-functional
• Non-conservative missense mutations 


  • cause addition of an incorrect amino acid into primary structure of protein
  • this amino acid does not have the same properties as the original one so protein had a different non-functional structure
• Beneficial mutations 


  • very rarely a protein synthesised results in a new & useful characteristic in the phenotype
  • e.g. mutation protein present in cell surface membranes of human cells mean HIV can't bind & enter these cells - makes people w this mutation immune to HIV infection
• Cause of mutations


  • occur spontaneously, often during DNA replication
  • rate of mutation increased by mutagens - chemical, physical or biological agents which cause mutations
  • loss of a purine base of pyrimidine base occurs spontaneously - absence of a base can lead to insertion of an incorrect base through complementary base pairing during DNA replication
  • free radicals can affect structures of nucleotides & also disrupt base baring during DNA replication
• Chromosome mutations


  • chromosome mutations affect a whole chromosome or a number of chromosomes within a cell rather than single genes or sections of DNA
  • caused by mutagens & occur during meiosis
  • mutations can be silent but do often lead to developmental difficulties
• Changes in chromosome structure

  • deletion - section of chromosome breaks off & is lost within cell
  • duplication - sections on chromosome get duplicated
  • translocation - section of one chromosome breaks off & joins another non-homologous chromosome
  • inversion - section of chromosome breaks off, is reversed & joins back onto chromosome
• Examples of mutagens


  • ionising radiations e.g. x-rays
  • deaminating agents
  • alkylating agents
  • base analogs
  • viruses
• Why do genes need regulation?

  • the entire genome of an organism is present in every prokaryotic or eukaryotic cell that contains a nucleus
  • this includes genes which are not needed, or those needed only some of time
  • therefore genes need to be turned on & off & rate of protein synthesis increase or decreased dependent upon need of each cell
• The 4 ways genes are regulated

  • transcriptional control
  • post-transcriptional control
  • translational control
  • post-translational control
• Defin exon

  coding region of DNA
• Define intron

  non-coding region of DNA
• Transcription factor

  protein or short non-coding RNA that can combine w a specific site on a length of DNA & inhibit or activate transcription of the gene
• Acetylation

  addition of acetyl or phosphate groups
• Methylation

  addition of a methyl group
• Transcriptional control includes

  • chromatin remodelling
  • histone modification
  • lac operon
  • cyclic AMP
• Chromatin remodelling

  • when chromatin is tightly wound (heterochromatin) around the histone proteins (as it is during cell division) transcription is physically impossible as RNA polymerase cannot access genes
  • when chromatin is loosely wound (euchromatin) transcription is possible - so protein synthesis only possible during interphase when cell is NOT dividing
• Histone modification

  • DNA coils around histones because they are positively charged & DNA is negatively charged
  • histones can be modified to increase/ decrease the degree of packing
• How are histones modified when less transcription is required?

  • addition of methyl groups (methylation)
  • makes histones more positive so DNA coils more tightly & less transcription occurs
• How are histones modified when more transcription is required?

  • addition of acetyl groups (acetylation) or phosphate groups
  • makes histones more negative so DNA coils less tightly & more transcription occurs
• Operon

  a group of genes that are under control of the same regulatory mechanism & are expressed at the same time
• 3 genes in lac operon

  • lacZ, lacY & lacA
  • they are structural genes as they code for enzymes: B-galactosidase, lactose permeate & transacetylase - and are transcribed onto a single long molecule of mRNA
  • involved in metabolism of lactose - synthesised by E.coli
• Function of E.coli

  • respire glucose & lactose - synthesises 3 inducible enzymes (lacZ, lacY, lacA) to metabolise lactose
• Function of lacZ (beta galactosidase)

  breaks down lactose into glucose & galactose
• Function of lacY (lactose permeate)

  increases uptake of lactose
• Function of lacA (transacetylase)

  transfers an acetyl group from acetyl-coA to B-galactosides
• Regions in lac operon

  • promoter region
  • operator region
  • regulatory gene
• Promoter region (lac operon)

  • where RNA polymerase attaches to DNA to start transcription
  • if partly covered by repressor protein, RNA polymerase cannot attach - transcription is prevented & mRNA can't be produced for protein synthesis
• Operator region

  • site where repressor protein binds
  • controls transcription of structural genes
  • if repressor protein bound to operator site it prevents transcription, & translation genes won't occur