ka6: mutations

• Mutations are changes in the DNA that can result in no protein or an altered protein being synthesised
• Single gene mutations involve the alteration of a DNA nucleotide sequence as a result of the substitution, insertion or deletion of nucleotides.
• Nucleotide substitutions — missense, nonsense and splice-site mutations
• • Missense mutations result in one amino acid being changed for another. This may result in a non-functional protein or have little effect on the protein.
• • Nonsense mutations result in a premature stop codon being produced which results in a shorter protein.
• • Splice-site mutations result in some introns being retained and/or some exons not being included in the mature transcript.
• Nucleotide insertions or deletions result in frame-shift mutations.
• Frame-shift mutations cause all of the codons and all of the amino acids after the mutation to be changed. This has a major effect on the structure of the protein produced.
• chromosome structure mutations — duplication, deletion, inversion and translocation.
• • Duplication is where a section of a chromosome is added from its homologous partner.
• Deletion is where a section of a chromosome is removed.
• Inversion is where a section of chromosome is reversed.
• Translocation is where a section of a chromosome is added to a chromosome, not its homologous partner.
• The substantial changes in chromosome mutations often make them lethal.
• Duplication allows potential beneficial mutations to occur in a duplicated gene whilst the original gene can still be expressed to produce its protein.
• Mutations are changes in the genome that can result in no protein or an altered protein being expressed.  When a change in the genomes produces a change in the phenotype the individual affected is called a mutant.

  Mutations arise spontaneously and at random but only occur rarely.
• These are alterations of the DNA base type or sequence of bases of a gene.  As a result, the sequence of amino acids in a protein is altered.  The altered protein is unable to carry out its normal function.
• Single gene mutations or point mutations; involve the alteration of a DNA nucleotide sequence as a result of the substitution, insertion or deletion of a nucleotide. This may occur in the protein-coding region or in one of the DNA sequences that regulates a gene. The latter can alter the expression of the gene rather than the protein formed
• Substitution – one nucleotide is replaced by another.

  
• Insertion – one nucleotide is added.

  
• Deletion – one nucleotide is lost.

  
• Substitutions only affect 1 triplet codon therefore only 1 amino acid in the protein is altered.  The resulting protein is slightly changed and its function is slightly altered.

  Single nucleotide substitutions can fall into 4 categories
• Substitutions only affect 1 triplet codon therefore only 1 amino acid in the protein is altered.  The resulting protein is slightly changed and its function is slightly altered.

  Single nucleotide substitutions can fall into 4 categories
• • Nonsense mutation – the altered codon no longer codes for an amino acid but is replaced with a stop codon.  It causes protein synthesis to be halted prematurely and results in a polypeptide chain shorter than normal.
• Splice-site mutation- result in some introns being retained and/or some exons not being included in the mature transcript.
• Insertion and deletion mutations result in a frame-shift in the triplet code.  Frame-shift mutations cause all of the codons and all of the amino acids after the mutation to be changed. This has a major effect on the structure of the protein produced.
• A mutation to a splice-site may alter the post-transcriptional processing of mRNA.

  A splice-site mutation occurs when a base is substituted, deleted or inserted at a site where introns are normally removed from the primary mRNA transcript.
• As a result introns may be left in the mRNA.  The altered mRNA may be translated into an altered protein which does not function properly.
• This type of mutation involves the breakage of one or more chromosomes and results in a change a section of a chromosome. 
• Inversion – a section of chromosome breaks free, rotates and rejoins

  
• Duplication – a section is added from the homologous partner.

  
• Deletion – a section of a chromosome is removed.

  
• Translocation – a section breaks free from 1 chromosome and becomes attached to another non-homologous chromosome.

  
• The substantial changes in chromosome mutations often make them lethal.
• Mutation is the only source of new variation.  Point mutations change DNA sequences of genes and are the means by which new alleles of genes arise.  Without mutations all organisms would be homozygous for all genes and no variation would exist.
• Most mutations are harmful or even lethal.  However, very rarely mutant alleles are formed that confer an advantage.  These new mutant alleles are the raw materials of evolution and are acted upon by natural selection.
• Gene duplication produces a second copy of a gene that is free from selection pressures.  Duplication allows potential beneficial mutations to occur in a duplicated gene whilst the original gene can still be expressed.  The mutations produce a new DNA sequence which can confer an advantage and in turn increase the organism’s survival chances.