IQ1: Mutations

• • All genetic variation between species and between individuals of the same species is a result of mutation
• Mutations can be beneficial or harmful. They can occur randomly as errors during cell replication and can affect a single gene, multiple genes or may involve entire chromosomes 
• • Environmental agents that cause mutations are known as mutagens.
• • Many mutagens are carcinogenic (cancer causing), causing changes in the cell cycle, resulting in increased cell division and masses of cells (tumours) 
• • Chemicals that can cause mutations if cells are exposed to them at high frequencies or for prolonged periods of time. 
  • Chemical mutagens cause a change in DNA that alters the function of proteins and, as a result, cellular processes and impaired.
• Examples of chemical mutagens include:

  • Ingested chemicals including alcohol, tar in tobacco smoke, some medications and chemicals in food e.g. food additives and preservatives (nitrites)
  • Environmental irritants and poisons such as organic solvents (e.g. benzene), cleaning produces, asbestos, pesticides, some hair dyes 
• Chemical mutations affect DNA in different ways

  • Interact with DNA to to produce mutagenic

    compounds 

  • Cause incorrect pairings of base pairs during 

  DNA replication

  • Some chemicals insert themselves into DNA 

  and change the shape of the molecule and its 

  chemical properties
• Naturally occurring mutagens are present at normal levels within natural environments and can be classified as:

  • Biological mutagens e.g. viruses, bacteria, fungi and their products 
  • Non-biological mutagens e.g. metals such as mercury and cadmium 
• Naturally occruing mutagens: Biolofical Mutagens

  • Microbes include viruses (e.g. Hep B, HIV, Rubella) and bacteria (Helicobacter). They are able to insert their own base sequences into DNA and in this way change the functioning of genes and trigger cancers. 
  • End products of metabolism- nitrosamines (nitrous acid/nitrite + amines)
• • Physical mutagens include particle radiation and electromagnetic radiation.
• Radiation is the emission or movement of energy through space or materials. In some cases, this energy can interrupt cellular processes and ionise molecules, damaging DNA; however, not all radiation is strong enough to do this. It can be divided into:

  • Ionising radiation
  • Non ionising radiation
• • Particle radiation:
  • Particles that have mass and energy, and may or may not have an electric charge e.g. alpha particles, protons, beta particles and neutrons. 
  • Radiation produced by nuclear fusion/nuclear fission
  • Occurs in nuclear power plants/nuclear weapons,
  • Extremely powerful mutagen
• • Electromagnetic radiation:
  • Radiation that does not have a mass or a charge e.g. visible light, UV light, x-rays and gamma rays. 
  • Radiant energy emitted by the electromagnetic field and exists on a spectrum as shown on the right.
  • Emitted by electrical devices of all kinds and is usually encountered into low levels
  • Divided into low frequency and high frequency radiation
• Physical mutagens - Ionising radiation

  • Includes both particle radiation and high frequency electromagnetic radiation (X-rays, gamma rays, high frequency end of the UV light spectrum (UVB, UVC))
  • Repeated long term exposure to ionising radiation can cause cancer. 
• Physical mutagens: Non-ionising radiation

  • Exists at the low frequency end of the EMS- infrared, microwaves, radio waves, visible light and UV (180-315 nm) 
  • Not associated with damage to DNA.
• Point mutations: A mutation that alters, adds or removes only ONE or VERY FEW nucleotides from a sequences of DNA or RNA is called a point mutation. 
• Types of Point Mutation:

  1. Substitution mutations

  • Silent mutations 
  • Neutral mutations 
  • Missense mutations 
  • Nonsense mutations 

  1. Frameshift mutations

  • Insertion
  • Deletion 
• Substitution mutations: one nucleotide is replaced by another
• Frameshift mutations: one or two nucleotides being either added or removed from the nucleotide sequence from the point onwards.
• • A silent mutation occurs when a substitution results in a new codon that still codes for the same amino acid therefore it will have no effect on the final polypeptide chain and no effect on the protein made
• Neutral mutations are changes in DNA that result in an amino acid of the same type as the original and so the change does not significant affect the structure of the protein.
• • Missense mutations are point mutations that result in an amino acid change. 
  • The functionality of the resulting protein is determined by whether or not the replacement amino acid is the same type as the original. 
• • Sickle cell anaemia occurs due to a missense mutation where the amino acid glutamic acid (Glu) is replaced by valine (Val) in the beta chain of the haemoglobin protein. 
• • Nonsense mutations change an amino acid to a stop codon. 
  • Stop codons signal translation to stop, resulting in the termination of protein synthesis.
• • Stop codons are an important part of protein synthesis but if it appears too early in an amino acid sequence, it can have severe effects. 
• • A nucleotide insertion adds one or two new nucleotides into the sequence and pushes the rest of the nucleotides back one or two places. This causes a significant effect on the polypeptide because as every codon is altered, so too is every amino acid they code for after the point of mutation → results in loss of functional protein
• A nucleotide deletion removes one or two nucleotides and pulls all the following nucleotides forwards by one or two places → causing a significant effect on the polypeptide because as every codon is altered, so too is every amino acid they code for after the point of mutation → results in loss of functional protein
• Chromosomal mutation: Mutations that affect large sections of a chromosome, typically multiple genes, are called chromosomal mutations.
• Types of chromosomal mutations: duplication, inversion, deletion, insertion, translocation
• Transposon: DNA segments that can move from one position to another in the chromosome
• Chromosomal mutations can be caused by transposons
• Inversion mutations involves a section of the sequence breaking off the chromosome, rotating 180 degrees and reattaching the same chromosome. Inversions may involve as few as two bases or they may involve several genes.
• Duplication mutations involve the replication of a section of chromosome that results in multiple copies of the same genes on that chromosome. This often increases gene expression, which can be harmful or beneficial depending on the gene involved.
• Deletion mutations remove sections of a chromosome. Deletions lead to disrupted or missing genes, which can have serious effects on growth and development. Chromosomal deletions are often fatal.
• Insertion mutations occurs when a section of one chromosome breaks off and attaches to a different chromosome. In eukaryotes, the effects of this type of mutation depends on whether the cell retains two copies of every gene. Other gametes may be missing the genes entirely.
• Translocation mutations is when a whole chromosome or a segment of a chromosome becomes attached to or exchanged with another chromosome or segment.
• Chromosomal abnormalities: Aneuploidy and polyploidy
• Aneuploidy occurs when one or more extra copies of an entire chromosome are made or an entire chromosome is missing, leading to an abnormal number of chromosomes in the cell. For e.g. down syndrome
• Polyploidy- organisms that contain more than two full sets of chromosomes. Errors during meiosis can result in diploid gametes. If one of these gametes is fertilised, it will result in a zygote with more than the usual two sets of chromosomes. In humans, polyploid zygotes don’t survive, however, it’s common in plants
• Mutations exert their effects at cellular, individual and population levels.