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

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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)
2. 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?