RVHS 11. DNA Mutations 9477

River Valley High School 1 2025 JC1 H2 Biology Lecture Topic 11: DNA Mutations River Valley High School 2025 JC1 H2 Biology Lecture Topic 11: DNA Mutations Name: ( ) Class: 25J____ Date: References Textbook Author Biology (9th Edition) Campbell and Reece Molecular Biology of The Cell (5th Edition) Alberts Johnson Lewis Raff Roberts Walter Genomes (2nd Edition) Brown Longman A-Level Course in Biology: Core Syllabus Volume 1 Hoh Biology: An Australian Focus (3rd Edition) Knox, Ladiges, Evans and Saint H2 Biology Syllabus 9477 (2025) Candidates should be able to use the knowledge gained in the following section(s) in new situations or to solve related problems. Related Topics Content Genetics and Inheritance Gene Expression Biological Evolution Natural Selection, Evolution and Biodiversity Learning Outcomes 2D. DNA Mutations a. Explain what is meant by the terms gene mutation and chromosome aberration. For gene mutation, knowledge of how substitution, addition and deletion could change the amino acid sequence (including frameshift) is required. For chromosomal aberration, knowledge of numerical ( including aneuploidy, as in the case of trisomy 21, i.e. Down syndrome) and structural aberration (including translocation, duplication, inversion, deletion) is required. b. Explain how gene mutations can result in diseases (including sickle cell anaemia). c. Discuss the bioethics of genetic maternal screening for mutations, including trisomy –21. Lecture Outline I. Introduction – DNA Mutations II. Point Mutations A. Types of Point Mutations B. Effects of Point Mutations C. Sickle Cell Anaemia III. Chromosomal Aberration A. Structural Alteration to Chromosomes B. Changes in Chromosome Number C. Diseases IV. Bioethical Issues of Genetic Maternal Screening A. Genetic Screening and Genetic Testing B. Maternal Genetic Screening C. Bioethical issues V. Mutagenesis

River Valley High School 2 2025 JC1 H2 Biology Lecture Topic 11: DNA Mutations Websites URL Description https://learn.concord.org/resources/779/mutations Interactive animation to explore how changing the DNA sequence can change the amino acid sequence of a protein. http://www.dnalc.org/resources/3d/17-sickle- cell.html A detailed 3D animation of how a single gene mutation can affect haemoglobin and result in sickle cell disease. https://learn.genetics.utah.edu/content/genetics/he moglobin Informative website detailing the sickle cell disease. https://www.nature.com/articles/s41431-021- 00970-2 Article on ethical landscapes of non -invasive prenatal testing

River Valley High School 3 2025 JC1 H2 Biology Lecture Topic 11: DNA Mutations I. Introduction – DNA Mutations • Genetic information is stored in linear sequences of base -pairs in DNA. Transcription and translation convert this genetic information into polypeptides, which become functional proteins. • These function as key intermediaries in the genetic control of phenotype. • A mutation is an inheritable change in the nucleotide base sequence of the DNA. This may result in an alteration to the organism’s phenotype (i.e. characteristic). • We can broadly classify DNA mutations into 2 categories: • DNA mutations can have numerous biological implications: o Mutations to proto -oncogenes and tumour suppressor genes can contribute to the onset of cancer (KIV: Cancer). o Mutations can also create new gene variants, or novel genes, contributing to the diversity of genes observed in a population. Genetic and phenotypic diversity allow for natural selection and evolution to take place (KIV: Biological Evolution) 1. 2. 3. Recall: Central Dogma of Molecular Biology What is the significance of a change in DNA structure and sequence? 4. Determines phenotype (Observable traits) Transcription Translation

River Valley High School 4 2025 JC1 H2 Biology Lecture Topic 11: DNA Mutations II. Point Mutations • When a DNA mutation results in only a single base-pair of a given gene being permanently changed, it is called a point mutation. • An alteration in the nucleotide sequence of a DNA will change the corresponding codon on the transcribed mRNA. o This may result in a change in the amino acid sequence of a polypeptide chain. o Which may change the 3 -D conformation of a protein, resulting in a change in its structure, properties, and function. o As a result, the phenotype of the organism may be altered. A. Types of Point Mutations o Base-pair Substitution This involves the replacement of one base pair with other nucleotides. o Base-pair Addition This involves the insertion of one base pair to a sequence of nucleotides. Such mutations can also be termed as base-pair insertions. o Base-pair Deletion This involves the removal of one base pair from a sequence of nucleotides.

River Valley High School 5 2025 JC1 H2 Biology Lecture Topic 11: DNA Mutations B. Effects of Point Mutations • The effect of a point mutation on the amino acid sequence depends on the type of gene mutation, and the number of affected nucleotide sequences. • When base-pair substitution of nucleotides is involved, it can result in the following effects: o Silent Mutations o Missense Mutations o Nonsense Mutations • Where base-pair addition or base-pair deletion of nucleotides is involved, it can result in a frameshift mutation. • Let us examine how different types of gene mutations to a given sequence of DNA can result in different effects of mutations. 1. Silent Mutations • A silent mutation occurs when the base-pair substitution of the nucleotide has no effect on the amino acid sequence. • In the above base-pair substitution, the codon “GGC” on the original mRNA molecule becomes “GGU”. However, both codons code for glycine. • This is due to the degenerate nature of the genetic code, where one single amino acid can be coded for by more than one codon. • As such, there is no change to the amino acid sequence , and no change to the properties of the R groups. • The interactions between R groups of the amino acid residue are the same, and the polypeptide chain bends and folds to produce the same, specific three-dimensional conformation. • This results in the formation of the same protein with the same properties and function. • The mutation is not observed at the phenotype level and therefore is described as silent. Original DNA sequence After base-pair substitution

River Valley High School 6 2025 JC1 H2 Biology Lecture Topic 11: DNA Mutations 2. Missense Mutations • Missense mutations occur when the base-pair substitution of nucleotides results in another amino acid being coded for. • Missense mutations can result in two different outcomes. A. Have little effect on the final protein B. Cause a major change to, the final protein. A. Little Effect on Protein • Missense mutations can have little effect on the final protein if the new amino acid: o has same or similar properties to those of the amino acid it replaces, ▪ E.g. Glycine to Alanine (Both are small and non-polar) o is in a region where the exact sequence of amino acids is not essential to the protein’s function. • The amino acid sequence is different, but the properties of the R groups are the same / similar. o E.g. mRNA codon is changed from “GAU” to “GAA” o Aspartic acid (GAU) is replaced by glutamic acid (GAA) o Both have negatively charged R groups, and can still form ionic bonds with another amino acid residue that has a positively charged (basic) R group. • The interactions between R groups of the amino acid residue are the same, and the polypeptide chain bends and folds to produce a protein with the same three-dimensional conformation as the original. • This results in