Unit 1: DNA and the Genome Sub-topic 6: Mutation

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1 Unit 1: DNA and the Genome Sub-topic 6: Mutation Page 1 of 24

2 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

The Genome and Mutations The genome of an organism is its genetic information encoded in DNA.

Mutations are changes in the genome that can result in no protein or an altered protein being expressed.

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.

3 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

4 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

Single Gene Mutations There are different categories of substitution and their names describe the affect they each have on the protein synthesised.

5 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

6 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

7 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

8 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 nonfunctional. 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: Amino acids produced: Base G inserted: Amino acids produced: C G A C C A A C G G C G Arginine Proline Theonine Alanine C G A G C C A A C G G C G Arginine Alanine Asparagine Glycine site of mutation Every codon is altered after the point of the mutation which could result in many amino acids being changed in the resultant protein. This alters both the structure and function of the protein. Page 8 of 24

9 Identify the types of frame-shift mutations shown below: Normal Mutation type 1 Mutation type 2 Describe how mutations Describe how mutations 1 and 2 arise and their effect on the protein produced: Mutation 1 Mutation 2 Page 9 of 24

10 Activity: Reading the frame. The exercise below uses the analogy of simple text to demonstrate the impact of different point mutations on the protein produced. Each word represents a triplet of bases or codon which codes for a particular amino acid. To help you visualise the protein coding sequence the "codons" have been placed in a "reading frame". For each example below circle where the mutation has occurred and state the type of mutation above each example. Example 1: Original the old man ran for the red bus Mutation the olb dma nra nfo rth ere dbus Example 2: Original the old man ran for the red bus Mutation the old man ran for her edb us Example 3: Original the old man ran for the red bus Mutation the old nan ran for the red bus Answer the following questions: Q1) Which type of mutation has the least effect on the meaning of the sentence i.e. if this was mrna which example would have the least effect on the final protein sequence? Give a reason for your answer. Page 10 of 24

11 Q2) Which of the examples of mutations given are frame-shift mutations? Give a reason for your answer. Q3) The table below shows some data on mutation in corn. Calculate the average number of mutations per million. Gene Number of gametes tested Number of mutations Rr 554, Ii 265, Susu 1,678,736 4 Shsh 2,469,285 3 Average number of mutations per million gamete Why is it necessary to convert to per million? From this information, what can you say about mutation frequency? Page 11 of 24

12 Mutation and Disease According to the 'National Human Genome Institute', most diseases have some sort of genetic factor. These disorders can be caused by a mutation in a single gene, multiple gene mutations, combined gene mutation and environmental factors, or by chromosome mutation or damage. DNA Repeat Sequences Nucleotide sequences can be repeated a number of times in a row in the DNA sequence. However, insertion could cause an abnormal number of these repeat sequences to occur. Repeat expansion disorders are a group of human diseases that are caused by the abnormal elongation of a DNA repeat sequence. See the diagram below showing a trinucleotide repeat which is made up of repeating 3 base pair sequences. This type of mutation increases the number of times that the short DNA sequence is repeated and can cause the resulting protein to function improperly. An example of a disease caused by this type of mutation is Huntington s disease. Gene mutations have been identified as the cause of many disorders including; Sickle Cell Anaemia, Cystic Fibrosis, Tay-Sachs disease, Huntington s disease, Haemophilia, and some Cancers. Activity: Using web sites such as; and classroom resources, make notes on a few of the genetic diseases mentioned above. Include; what type of mutation has caused it? what is the frequency of occurrence? is the mutation confined to a specific area or ethnic race? what are the symptoms associated with each mutation? are any of the mutations beneficial or are they detrimental? Page 12 of 24

13 Disease 1: Disease 2: Diseases caused by mutation Disease 3: Disease 4: Page 13 of 24

There are 2 types of chromosome mutation: changes in the chromosome structure changes in the chromosome number Chromosome structure mutations

14 Chromosome Mutations During gamete formation (meiosis) the homologous (matching) pairs of chromosomes line up at the equator of the cell. This is the stage where mutations involving changes to the chromosome structure can occur. There are 2 types of chromosome mutation: changes in the chromosome structure changes in the chromosome number Chromosome structure mutations are; Duplication Inversion Deletion Translocation Memory Aid: DID T Changes in Chromosome Structure Write a statement describing each chromosome mutation shown below; a. Translocation b. Inversion Page 14 of 24

15 c. Deletion d. Duplication The four diagrams below show different chromosome mutations that can affect a chromosome. Write the name of each mutation shown in the correct box. a) b) c) d) Page 15 of 24

16 Change in Chromosome Number Mutation can cause the chromosome number to be changed e.g. whole extra sets of chromosomes in the gamete. Most chromosome mutations are harmful; however, some provide advantages to the organism. Polyploidy Mutation and Evolution Most organisms have two sets of chromosomes in their body cells. They are diploid (2n). When an organism has cells with more than two sets of chromosomes it is referred to as polyploidy (multiple sets of 3n or above). Polyploidy is rare in animals but common in plants. Mutations and gene duplication are important in evolution as they result in polyploidy. During gamete formation (meiosis) the homologous pairs (matching parental pairs) of chromosomes line up at the equator of the cell. It is at this point where mutations involving changes to the chromosome number can occur. Errors during the separation of chromosomes during cell division can result in cells with whole genome duplications. If the spindle fibres fail to pull the chromosomes apart, they remain together and move as one into the new gamete. Spindle fibre failure is known as non-disjunction. This can happen to whole sets of chromosomes if all the spindle fibres fail as shown in the diagram below. This is called complete non-disjunction. Diagram All spindle fibres fail. All chromosomes move together into a gamete. Page 16 of 24

Polyploidy is responsible for the evolution of many of the 'modern and improved' food crops we see today. Polyploidy can be induced in plants using mutatgenic agents such as colchicines.

17 Polyploidy is responsible for the evolution of many of the 'modern and improved' food crops we see today. Polyploidy can be induced in plants using mutatgenic agents such as colchicines. The diagram below outlines how polyploidy can occur in plants. Plant Variety A Plant Variety B P 2n 2n Gametes nn - n n Gametes n n - n n nn nnn nnn F1 possibilities nnn nnn The brassica family is shown in the diagram below. Each of the examples has been produced as a result of polyploidy naturally in nature. Scientists have used this ability to produce the many variations of different brassica we have today. This type of mutation provides crop plants with a variety of different advantages which are of economic importance. Page 17 of 24

18 Polyploidy can be extremely useful to both the plants but also commercially as these plants have many desirable characteristics. Read Torrance p 72 Economic Importance of polyploidy and list some of these advantages below. When polyploidy plants are produced by crossing different varieties the resulting hybrid often shows the enhanced characteristics; improved growth, increased fertility or resistance to disease. This we call hybrid vigour. Many plants are polyploid e.g. Durum wheat used to make pasta is tetraploid while White bread wheat is hexaploid. How many sets of chromosomes does each of the wheat examples possess? Durum wheat = White bread wheat = Page 18 of 24

19 The diagram below shows stages in the evolution of a species of modern wheat (Triticum vulgare) through polyploidy. Page 19 of 24

20 Decide if each of the following statements is true or false and give an explanation for your decision below: 1. Hybrid A is sterile as it is unable to form homologous pairs in meiosis. True False Explanation: 2. The chromosome number of hybrid B is 21. True False Explanation: 3. The doubling of the chromosome number is due to fusion of gametes at fertilisation. True False Explanation: 4. Two species that are fertile polyploids are T. durum and T. vulgare True False Explanation: Page 20 of 24

21 Activity 1: Task A: Research polyploidy in plants and the importance in the evolution of modern crop species. Choose two to plants from the following polyploids; banana, potato, swede/turnip, oil seed rape, wheat, strawberry. Task B: Read Torrance p 73 and make notes of the rarity of polyploidy in animals using the Viscacha rat. Record your research notes below Page 21 of 24

22 Activity2: Collect a copy of the Polyploidy and Evolution work booklet and answer the questions. Page 22 of 24

23 Mutations Summary Gene Mutation Chromosome Mutation Replacement of one base pair for another. Addition or removal of a base pair Change in the number of chromosomes Change in the structure of the chromosome S I P D D I D T The different effects that a single gene mutation has on the protein can be described as: i) ii) iii) iv) v) Description Effect Splice site mutation Regulatory site mutation Could prevent a splice site or produce an additional splice causing introns to be left in the mature transcript. Can result in the absence or excess of the protein expressed. Page 23 of 24

24 1.6 Mutations How well do you rate your knowledge and understanding? Complete: Row 1 before your Unit assessment Row 2 before your Prelim Row 3 before your May exam A mutation is a random change in the genome, causing no protein or an altered protein to be produced. Mutation is random and the frequency is low but can be induced by mutagenic agents. Mutations can be classified as either chromosome or gene. 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 or a single base pair. Substitution, deletion and insertion are single gene point mutations which can result in missense, nonsense, neutral or splice site mutations (altering post-transcriptional processing). Insertions and deletions result in frame-shift mutations or expansion of a nucleotide sequence repeat. Regulatory sequence mutations can alter gene expression. Mutations at splice sites can alter the mrna mature transcript produced affecting the splicing of introns. Mutations can cause abnormal replication of repeat sequences which can result in 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 whole genome duplications. Polyploidy has a beneficial impact on plants, especially crops. Page 24 of 24

Genes and Proteins in Health. and Disease

Genes and Proteins in Health. and Disease Genes and Health and I can describe the structure of proteins All proteins contain the chemical elements Carbon, Hydrogen, Oxygen and Nitrogen. Some also contain sulphur. Proteins are built from subunits