Genetics and Evolution

Molecular Basis of Inheritance - Deamination

  • DNA undergoes various types of chemical modifications
  • One such modification is called deamination
    • Deamination is the removal of an amino group from a molecule
    • In the case of DNA, deamination occurs in nitrogenous bases
  • Deamination can lead to the formation of different nucleotides and thus affect genetic information

Deamination in Cytosine

  • Cytosine is one of the four nitrogenous bases present in DNA
  • When cytosine undergoes deamination, it converts into uracil
  • Uracil is normally found in RNA, but not in DNA
  • The presence of uracil in DNA can lead to errors during DNA replication and transcription

Example:

  • If a cytosine base undergoes deamination and turns into uracil
  • During replication, instead of pairing with guanine, uracil pairs with adenine
  • This leads to the substitution of a cytosine with a thymine in the newly synthesized DNA strand

Deamination in Adenine

  • Adenine, another nitrogenous base in DNA, can also undergo deamination
  • Deamination of adenine converts it into hypoxanthine
  • Hypoxanthine is not normally found in DNA, but it is found in RNA

Example:

  • If an adenine base undergoes deamination and turns into hypoxanthine
  • During replication, instead of pairing with thymine, hypoxanthine pairs with cytosine
  • This leads to the substitution of an adenine with a guanine in the newly synthesized DNA strand

Consequences of Deamination

  • Deamination can cause permanent changes in the DNA sequence, leading to mutations
  • Mutations are important drivers of evolutionary change
  • Deamination can also be repaired by DNA repair mechanisms in the cell

Equations:

  1. Cytosine (C) -> Uracil (U)
  1. Adenine (A) -> Hypoxanthine

Summary:

  • Deamination is the removal of an amino group from a molecule
  • Cytosine can convert into uracil through deamination
  • Adenine can convert into hypoxanthine through deamination
  • Deamination can lead to DNA mutations and evolutionary changes

Slide 11

  • DNA undergoes various types of chemical modifications
  • One such modification is called deamination
  • Deamination is the removal of an amino group from a molecule
  • Deamination can lead to the formation of different nucleotides
  • These nucleotides can affect genetic information

Slide 12

  • Cytosine is one of the four nitrogenous bases present in DNA
  • Deamination of cytosine converts it into uracil
  • Uracil is normally found in RNA, not in DNA
  • The presence of uracil in DNA can lead to errors during replication and transcription
  • During replication, uracil pairs with adenine instead of guanine

Slide 13

  • Adenine is another nitrogenous base found in DNA
  • Deamination of adenine converts it into hypoxanthine
  • Hypoxanthine is not normally found in DNA, but in RNA
  • During replication, hypoxanthine pairs with cytosine instead of thymine
  • This leads to the substitution of adenine with guanine in the DNA strand

Slide 14

  • Deamination can cause permanent changes in the DNA sequence
  • These changes are called mutations
  • Mutations are important drivers of evolutionary change
  • They can lead to new traits or variations in a population
  • Natural selection acts on these variations to shape evolutionary processes

Slide 15

  • Deamination can be repaired by DNA repair mechanisms in the cell
  • One such mechanism is the Base Excision Repair (BER) pathway
  • BER recognizes and removes the damaged base (e.g., uracil)
  • The gap is then filled with the correct nucleotide by DNA polymerase
  • Other repair mechanisms include Mismatch Repair and Nucleotide Excision Repair

Slide 16

  • Deamination can also be induced by environmental factors
  • Exposure to certain chemicals, radiation, or metabolic processes can cause deamination
  • Example: Nitrous acid, a common mutagen, can cause deamination of cytosine to uracil
  • Environmental factors can increase the rate of mutations and affect genetic diversity
  • This plays a role in evolution and adaptation to changing environments

Slide 17

  • Deamination is not limited to DNA alone
  • RNA also undergoes deamination, leading to changes in genetic information
  • Example: Deamination of adenosine (A) in RNA converts it into inosine (I)
  • Inosine can pair with cytosine (C), uracil (U), or adenine (A) during RNA synthesis
  • This flexibility allows for alternative base pairings and increased diversity in RNA molecules

Slide 18

  • Deamination can have both positive and negative effects on organisms
  • Positive effects: Deamination can contribute to genetic diversity and adaptation
  • Negative effects: Deamination can lead to DNA mutations and genetic disorders
  • Understanding the impact of deamination is crucial in fields like medicine and evolutionary biology

Slide 19

  • Equations:
    1. Cytosine (C) -> Uracil (U)
    2. Adenine (A) -> Hypoxanthine
    3. Adenosine (A) -> Inosine (I)

Slide 20

  • Summary:
    • Deamination is the removal of an amino group from a molecule
    • Cytosine can convert into uracil through deamination
    • Adenine can convert into hypoxanthine through deamination
    • Deamination can lead to DNA mutations and evolutionary changes
    • Repair mechanisms exist to fix deamination-induced damage in DNA and RNA

Slide 21

  • Importance of studying deamination:
    • Understanding deamination helps in understanding the molecular basis of genetic diseases
    • It provides insights into how mutations occur and their impact on organisms
    • Deamination also plays a role in the evolution and adaptation of species

Slide 22

  • Factors influencing deamination:
    • Environmental factors: Exposure to mutagens such as radiation or certain chemicals
    • Metabolic processes: Natural processes in the body that can cause deamination
    • DNA repair mechanisms: The efficiency of repair mechanisms can influence the extent of deamination-induced damage

Slide 23

  • Examples of genetic diseases caused by deamination:
    • AICAR Transformylase/IMP Cyclohydrolase Deficiency (ATIC): Caused by a mutation that impairs the conversion of AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) to IMP (inosine monophosphate)
    • MTHFR (Methylenetetrahydrofolate Reductase) Deficiency: Mutations in the MTHFR gene affect the metabolism of folate, leading to various health problems
    • PKU (Phenylketonuria): Caused by a mutation in the phenylalanine hydroxylase gene, resulting in the accumulation of phenylalanine

Slide 24

  • Examples of adaptive deamination:
    • Saltation: Rapid adaptive evolution that occurs due to the accumulation of deamination-induced mutations in a population over a short period
    • Somatic hypermutation: A natural process in immune cells where deamination-induced mutations increase the diversity of antibodies
    • Evolution of Antarctic fish: The presence of antifreeze glycoproteins in some Antarctic fish is believed to be a result of adaptive deamination

Slide 25

  • Common methods to study deamination:
    • DNA sequencing: Identifying specific changes in the DNA sequence caused by deamination
    • Polymerase Chain Reaction (PCR): Amplifying specific regions of DNA for further analysis
    • Gel electrophoresis: Separating DNA fragments based on their size, allowing for the detection of mutations caused by deamination
    • Computational analysis: Using bioinformatics tools to analyze large-scale genomic data for deamination patterns

Slide 26

  • Equations:
    1. Cytosine (C) -> Uracil (U)
    2. Adenine (A) -> Hypoxanthine
    3. Adenosine (A) -> Inosine (I)
    4. AICAR -> IMP

Slide 27

  • Applications of deamination in research and medicine:
    • Forensic DNA analysis: Studying deamination patterns in DNA samples can help in identifying individuals
    • Cancer research: Mutations caused by deamination can be associated with certain types of cancers and aid in understanding their development
    • Drug development: Understanding deamination mechanisms can help in designing therapeutic strategies targeting specific mutations

Slide 28

  • Summary:
    • Deamination is a chemical modification of DNA bases that can lead to mutations
    • Cytosine can convert into uracil and adenine can convert into hypoxanthine through deamination
    • Deamination has important implications in genetic diseases, evolution, and adaptation
    • Repair mechanisms can mitigate the effects of deamination, but some mutations may persist
    • Studying deamination helps in understanding the molecular basis of genetic disorders and has various applications in research and medicine

Slide 29

  • References:
    • Watson JD, et al. (2007). Molecular Biology of the Gene. 6th edition.
    • Nelson DL, et al. (2019). Lehninger Principles of Biochemistry. 7th edition.
    • Alberts B, et al. (2017). Molecular Biology of the Cell. 6th edition.

Slide 30

  • Questions for discussion:
    1. What are the consequences of deamination in DNA?
    2. How can deamination lead to genetic disorders?
    3. Explain the role of repair mechanisms in mitigating deamination-induced damage.
    4. Provide an example of adaptive deamination in evolution.
    5. How can deamination be studied in a laboratory setting?