CfE Higher Biology Pupil Course Notes Unit 1: DNA and the Genome Sub-topic 6: Mutation Page 1 of 24 CfE Higher Biology Pupil Course Notes On completion of this topic I will be able to state that: mutations are random changes in the genome, causing no protein or an altered protein to be produced mutation frequency is low but can be induced by mutagenic agents mutations can be classified as either chromosome or gene mutations mutations are important in the evolutionary pathway of organisms and can offer a selective advantage or disadvantage to the organism single gene mutation results from a change in the DNA nucleotide sequence single nucleotide substitutions include neutral, missense, nonsense and splice site mutations insertion and deletion gene mutation results in frame-shift mutation or expansion of a nucleotide sequence repeat regulatory sequence mutations can alter gene expression splice sites mutations can alter the mRNA mature transcript produced by affecting the splicing of introns mutations can cause abnormal replication of repeat sequences which can result in disease (such as Huntington’s disease) different chromosome structure mutations are; duplication, deletion, translocation and inversion non-disjunction during the separation of chromosomes during cell division can result in cells with extra chromosomes or whole genome duplications polyploidy has a beneficial impact on plants especially crops. Prior Learning for this Topic. Unit 1.5 Proteins and Enzymes The variety of protein shapes and different functionality arise from their specific sequence of amino acids. Unit 3.4 Adaption, natural selection and the evolution of species a mutation is a random change to genetic material mutations can be neutral, or confer an advantage or a disadvantage on an organism mutations are spontaneous and the only source of new alleles environmental factors, such as radiation can increase the rate of mutation. Page 2 of 24 CfE Higher Biology Pupil Course Notes The Genome and Mutations The genome of an organism is its genetic information encoded in DNA. When irreversible changes occur to the genome this changes the genetic code which changes the protein it encodes. Mutations are changes in the genome that can result in no protein or an altered protein being expressed. Mutations can occur randomly or be induced and can alter alleles, genes, gene expression or the number or structure of the chromosomes. Living cells undergo frequent chemical change especially during replication. Most of these changes are quickly repaired by the cell’s DNA machinery. Those that are not result in mutation. When a change in the organism’s genotype causes a change to the phenotype the individual affected is called a mutant. Changes in the genetic code due to mutation can lead to genetic variation and are therefore the driving force of evolution. Without mutation there would be no variation, without variation there would be no evolution. Some mutations however have the potential to develop disease. Mutations could result from: a change in the genes or change in the chromosomes Chromosome mutation Gene mutation Although mutations can occur naturally they can also be induced by mutagenic agents such as; radiation: ganmma rays, X rays, UV rays high temperatures chemicals such as colchicine. Page 3 of 24 CfE Higher Biology Pupil Course Notes Gene Mutations Single Gene Mutation Single gene mutations involve the alteration of a DNA nucleotide sequence as a result of the substitution, insertion or deletion of nucleotides. The mutation could occur within the protein coding region of a gene causing an alteration in the type of amino acid coded for, or in one of the DNA sequences elsewhere on the chromosome that is involved in the regulation of the gene. A gene mutation at a regulatory gene site could therefore alter the expression of the gene by resulting in the absence or over production of a protein. For a protein to function properly it is essential that it has the correct amino acids. If the nucleotide base sequence is changed, it could change the amino acid coded for and therefore affect the structure and functionality of the protein produced. During protein synthesis, DNA is transcribed into mRNA and then translated into proteins. Any alteration to the nucleotide base sequence most often results in a different protein or non-functioning protein being synthesised. If the mutation occurs at a point that affects the regulation of the gene then no protein is synthesised and this would alter the phenotype. This is outlined in the diagram below. Diagram Page 4 of 24 CfE Higher Biology Pupil Course Notes Single Gene Mutations There are different categories of substitution and their names describe the affect they each have on the protein synthesised. If the substitution mutation has no effect on the protein produced it is said to be neutral, whereas others such as; missense, nonsense and splice- site can have a significant impact on the protein manufactured. Substitution Mutations Substitution mutation occurs when one nucleotide base pair is replaced for another. This affects only one codon. Sickle cell anaemia is a disease that is caused by a substitution mutation and it’s affect is shown below. Normal haemoglobin DNA Mutant haemoglobin DNA Normal haemoglobin Sickle cell haemoglobin Describe how the type of mutation shown above arises and its effect on the protein produced: ____________________________________________________________________ ____________________________________________________________________ Page 5 of 24 CfE Higher Biology Pupil Course Notes Generally, substitution causes only a minor alteration to the protein as it only affects one codon therefore one amino acid. However, if this occurs at a critical point in the protein then it could cause a major defect. e.g. sickle cell anaemia. (1) Missense mutation Missense mutation alters the nucleotide sequence by changing a base pair. This means that the codon is on the mature transcript is changed and now codes for a different amino acid. The change may not affect the protein, may be beneficial to protein function, or may be dangerous e.g. If the codon for leucine CUU is changed to CCU, the amino acid proline will be produced instead of leucine. Missense DNA strand DNA strand mRNA UUUCUUACAAAU mutation UUUCCUACAAAU amino acid phe leu thr aspn phe pro thr aspn Why is this type of point mutation called missense? _________________________________________________________________________ _________________________________________________________________________ (2) Nonsense mutation This type of mutation alters the nucleotide sequence so that a stop codon is coded for in place of an amino acid. A stop codon signals the end of the translation process and stops protein production. If this process is ended too soon, the amino acid sequence is cut short and the resulting protein is shorter than it should be. As a result of the missing amino acids the protein is most often non-functional. Page 6 of 24 CfE Higher Biology Pupil Course Notes Nonsense DNA strand DNA strand mRNA CGUAGUUAUGGC mutation CGUAGUUAAGGC amino acid gly ser tyr gly gly ser STOP Explain why this term is used to describe a nonsense mutation? ____________________________________________________________________ ____________________________________________________________________ _________________________________________________________________________ How does it affect the protein made? ____________________________________________________________________ (3) Splice- site mutation From Unit 1.3 you learned that non coding regions of DNA called introns are cut from the primary transcript of mRNA and the exons are spliced together during transcription. This forms a continuous mRNA coding sequence of nucleotides in the mature mRNA transcript. This ensures that the correct amino acids are coded for and in their correct order to produce the desired protein. If a mutation occurs at a splice site one or more introns may be left in the mature mRNA transcript. The altered mRNA code could translate into an altered protein which is non-functional or doesn’t function correctly. Thalassemia (type of anaemia) results from a mutation at a splice- site which causes a defect in the manufacture of the protein haemoglobin. Explain how a mutation in a splice- site could affect the protein produced. ____________________________________________________________________ ____________________________________________________________________ Page 7 of 24 CfE Higher Biology Pupil Course Notes Frame-shift Mutations Nucleotide insertions and deletions result in the frame -shift mutations or an expansion of the nucleotide sequence repeat. Since the nucleotide sequences are read in groups of three bases (a codon), any addition or deletion of a base pair will cause a shift in the whole 'reading frame' of the mature mRNA transcript i.e. every amino acid coded for after the site of the mutation will be altered. Insertion and deletion both lead to major change in the protein since each causes a large proportion of the mRNA to be misread. The protein structure will contain many different amino acids and it is usually rendered non- functional. For example, if the original transcribed DNA sequence is CGA CCA ACG GCG ..., if base G is inserted between the first and second groupings, the reading frame will be shifted as shown below. Original sequence: C G A C C A A C G G C G Amino acids produced: Arginine Proline Theonine Alanine Base G inserted: C G A G C C A A