DNA mutations

• 🗸 alterations in the sequence of nucleotides within a DNA molecule.

  🗸 mutations can occur in various ways, and their consequences can range from negligible to severe, depending on factors such as the location and nature of the mutation.

  DNA Mutation
• 🗸 agents that can induce genetic mutations by altering the DNA sequence.

  🗸 can be natural or artificial substances that cause changes in the genetic material of an organism.

  🗸 can interact with DNA in various ways, leading to errors in replication, transcription, or repair processes.

  Mutagens
• 3 Types of Mutagens

  1. Chemical mutagens
  2. Physical mutagens
  3. Biological mutagens
• What are substances that directly interact with DNA molecules, causing changes in the nucleotide sequence?

  Chemical mutagens
• Alkylating agents:

  These chemicals add alkyl groups to DNA bases, leading to base modifications and DNA strand breaks.

  Examples include ethylmethanesulfonate (EMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
• Base analogs:

  These compounds resemble normal DNA bases but have different hydrogen-bonding properties, leading to base-pairing errors during replication.

  Examples include 5-bromouracil and 2-aminopurine.
• Polycyclic aromatic hydrocarbons (PAHs):

  Found in tobacco smoke, charred foods, and environmental pollutants, PAHs can bind to DNA and form bulky adducts, causing DNA damage.
• Produced by certain molds, aflatoxins can form DNA adducts and cause mutations, increasing the risk of liver cancer.

  Aflatoxins
• Example of Chemical mutagens

  • Alkylating agents
  • Base analogs
  • Polycyclic aromatic hydrocarbons (PAHs)
  • Aflatoxins
• agents that cause DNA damage through physical means, such as radiation.

  Physical mutagens
• 🗸 agents of biological origin that can induce mutations

  Biological mutagens
• UV light can induce the formation of thymine dimers in DNA, where adjacent thymine bases become covalently linked, leading to replication errors and mutations.

  Ultraviolet (UV) radiation
• Ionizing radiation


  X-rays and gamma rays can cause DNA strand breaks, base modifications, and chromosomal rearrangements, leading to mutations and genetic instability.
• Some viruses, such as retroviruses, integrate their genetic material into the host cell's genome, potentially disrupting gene function and causing mutations.
• Transposable elements:

  These DNA sequences, also known as "jumping genes," can move within the genome and insert themselves into new locations, potentially disrupting gene function or causing chromosomal rearrangements.
• ✪ CAUSES OF MUTATION

  ● Spontaneous Mutations

  ● Replication Errors

  ● Environmental Factors

  ● DNA Repair Mechanisms

  ● Transposons

  ● Viral Integration

  ● Recombination Errors
• SPONTANEOUS MUTATIONS


  
  

  🗸These mutations arise naturally due to errors in DNA replication, repair, or recombination processes.

  🗸 During DNA replication, the enzyme responsible for copying DNA, DNA polymerase, occasionally inserts an incorrect nucleotide, leading to a mismatched base pair.

  🗸 Similarly, exposure to environmental factors such as radiation or chemical mutagens can induce changes in DNA structure, leading to mutations.
• REPLICATION ERRORS


  � DNA replication is a highly accurate process, but it's not perfect.

  🗸 Occasionally, DNA polymerase may make errors while copying the DNA sequence.

  🗸 These errors can result in base substitutions (replacing one nucleotide with another), insertions (adding extra nucleotides), or deletions (removing nucleotides).

  🗸 Such mistakes can occur randomly or due to the influence of external factors
• ENVIRONMENTAL FACTORS


  🗸 Exposure to certain environmental agents can increase the likelihood of DNA mutations.

  🗸 These agents, known as mutagens, include ionizing radiation (such as X-rays and gamma rays), ultraviolet (UV) radiation from the sun, certain chemicals (like those found in tobacco smoke or industrial pollutants), and some viruses.

  🗸 Mutagens can directly damage DNA or interfere with its replication and repair mechanisms, leading to mutations.
• DNA REPAIR MECHANISMS


  🗸 Cells have sophisticated DNA repair mechanisms to fix errors that occur during DNA replication or damage caused by environmental factors.

  🗸 However, these repair systems can sometimes introduce mutations themselves. For instance, if a repair enzyme makes an error while fixing damaged DNA, it can lead to a mutation.
• TRANSPOSONS


  🗸 also known as "jumping genes"

  🗸 DNA sequences that can move from one location in the genome to another.

  🗸 When transposons move, they can disrupt the normal DNA sequence, leading to mutations.

  🗸 Additionally, transposons can sometimes carry other genetic material with them, further altering the DNA sequence at their insertion site.
• VIRAL INTEGRATION


  🗸 Some viruses, such as retroviruses, integrate their genetic material into the host cell's genome as part of their replication cycle.

  🗸 This integration can disrupt normal gene function or regulation, potentially leading to mutations or other genetic changes.
• DNA RECOMBINATION ERRORS


  🗸 During meiosis, the process of cell division that produces gametes (sperm and egg cells), DNA recombination occurs, where segments of DNA from two homologous chromosomes are exchanged.

  🗸 Errors in this process can lead to the insertion, deletion, or rearrangement of DNA segments, resulting in mutations.
• ● Entire sections of chromosomes can be rearranged or lost.

  ● One or more genes may be swapped or deleted.
• ✪ TYPES OF MUTATIONS

  • POINT MUTATIONS
  • FRAMESHIFT MUTATIONS
  • SILENT MUTATIONS
  • MISSENSE MUTATIONS
  • NONSENSE MUTATIONS
  • INSERTION AND DELETION MUTATIONS
  • REPEAT EXPANSIONS
• How many daughter cells does Meiosis have?

  Four daughter cells
• POINT MUTATIONS

  🗸 Involve changes to a single nucleotide base in the DNA sequence. They can occur through several mechanisms:

  ● Substitution

  ● Insertion

  ● Deletion
• ○ One nucleotide is replaced by another.

  ○ For example, adenine (A) may be replaced by guanine (G), resulting in an Ato-G substitution mutation

  Substitution
• ● Insertion


  ○ One or more nucleotides are added to the DNA sequence.

  ○ This can lead to a shift in the reading frame, altering the subsequent amino acid sequence.
• ● Deletion


  One or more nucleotides are removed from the DNA sequence, which can also cause a shift in the reading frame and affect the resulting protein.
• FRAMESHIFT MUTATIONS


  🗸 Occur when the addition or deletion of nucleotides causes a shift in the reading frame of the genetic code.

  🗸 This alteration can lead to a completely different amino acid sequence downstream of the mutation site.

  🗸 Often have more severe consequences than point mutations because they can drastically alter the structure and function of the resulting protein.
• SILENT MUTATIONS


  🗸 Are point mutations that do not result in any change to the amino acid sequence of the protein.

  🗸 This occurs when the altered codon still codes for the same amino acid due to the redundancy of the genetic code.

  🗸 Typically have no detectable effect on the phenotype.
• MISSENSE MUTATIONS


  🗸 Are point mutations that change a single nucleotide in a way that leads to the substitution of one amino acid for another in the protein sequence.

  🗸 Depending on the specific amino acid change and its location within the protein, missense mutations can have varying effects on protein function.
• NONSENSE MUTATIONS


  🗸 are point mutations that introduce a premature stop codon into the mRNA sequence, leading to the premature termination of protein synthesis. 🗸 As a result, the resulting protein is often truncated and nonfunctional.
• INSERTION AND DELETION MUTATIONS


  🗸 Involve the addition or removal of one or more nucleotides from the DNA sequence.

  🗸 These mutations can disrupt the reading frame, leading to frameshift mutations, or they can occur in multiples of three nucleotides, which may not cause a frameshift but can still alter the amino acid sequence of the resulting protein.
• REPEAT EXPANSIONS


  🗸 Involve the abnormal increase in the number of repeated sequences of nucleotides within a gene.

  🗸 These expansions can occur in coding or non-coding regions of the DNA and are associated with several genetic disorders, including Huntington's disease and Fragile X syndrome.

  🗸 These are some of the main types of DNA mutations, each with its own specific consequences for gene expression, protein function, and ultimately, the phenotype of an organism.