Epigenetics, Gene Regulation, and DNA Replication

Grooming and Epigenetics

• Grooming behaviors in mice influence gene expression through a process called methylation.
  • Mice lick their pups, which leads to changes in the glucocorticoid receptor gene.
  • This receptor is crucial for stress regulation:
  • Active receptor → reduced stress → healthier pups.
  • Inactive receptor → increased stress.
• This illustrates how environmental factors (like licking) can influence genetic expression, showcasing epigenetics.

Agouti Gene Example

• The Agouti gene affects mouse characteristics:
  • Causes obesity and diabetes.
  • Alters fur color, leading to visual changes.
• Feeding mice vitamin B12 and folic acid can change the methylation state of the Agouti gene, turning it off and minimizing health impacts.

Temperature Effects on Genes

• Environmental temperature impacts gene expression:
  • At temperatures below 28 degrees, certain pathogenic genes are activated in fleas, making them more aggressive in feeding on hosts, thus facilitating disease transmission.
  • When fleas bite mammals, those pathogenic genes are turned off due to the higher internal body temperature (37 degrees).

Importance of Gene Regulation

• Understanding gene regulation is essential for developing targets for modifying diseases.
• Various examples demonstrate how regulation impacts health and disease outcomes. Memorization of these examples may be suggested by the instructor for the test.

DNA Replication Overview

• DNA replication relies heavily on base pairing.
  • Key base pair rules in DNA:
  • Adenine (A) pairs with Thymine (T)
  • Guanine (G) pairs with Cytosine (C)
• Accurate base pairing is crucial to ensure functional DNA replication.
• Enzymes play fundamental roles in unwinding DNA and facilitating base pairing during replication.

Importance of Accuracy in DNA Replication

• The accuracy of DNA replication is critical:
  • Errors in replication can lead to dysfunctional proteins or diseases.
  • Enzymes have very low error rates, approximately 1 error per 10^8 base pairs added.
• While it may seem beneficial to have perfect replication, a certain level of mistakes can facilitate adaptation in rapidly changing environments, e.g., exposing bacteria to antibiotics.

Evolution and Antibiotic Resistance

• Bacteria find mutations that confer an advantage in survival against antibiotics.
  • Adaptive mutations are random—most bacteria will die, but rare mutants survive and flourish.
• Evolution relies on genetic variations that allow organisms to adapt and thrive in changing conditions, leading to faster replacement of ineffective strains.

Polymerases and Functionality

• DNA polymerases are crucial for connecting bases during DNA strand elongation.
• The functionality of polymerases affects the organism's viability:
  • Faulty polymerases may lead to fatal genes not being expressed correctly, critically impacting survival.

HIV Lifecycle

• Understanding HIV lifecycle is essential in targeting viral replication:
  • Reverse transcriptase converts viral RNA into DNA, an important step for viral replication.
  • Antiviral treatments (e.g., Acyclovir - ACT) target these crucial processes to inhibit further disease spread.
• HIV uses protease to process viral proteins, which can also be inhibited as part of therapy, emphasizing the multiple points of intervention possible based on basic biological principles.

Epidemiology Example

• Analyzing outbreaks can reveal connections between patients and sources of infection, e.g., organ transplant-related transmissions of viruses.
• Tracking pathogen transmission routes showcases the need for comprehensive testing and coordination among health officials to prevent outbreaks from escalating.
• Immunocompromised individuals are at a heightened risk due to their vulnerable health status.

Conclusion

• Overall, the intricate relationships between DNA replication, gene expression, and environmental impacts illustrate the complexity of genetics.
• There is a balance between genetic stability for function and flexibility for adaptation, crucial for survival and evolution in varying environments.