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Gene Regulation in Bacteria: Lac and Trp Operons

  • Overview of Gene Regulation in Bacteria
    • Bacterial genetics often involves operons, which are clusters of genes regulated together.
    • Key examples include the lac operon and trp operon.
  • Lactose (Lac) Operon
    • The lac operon is a model for understanding gene regulation in bacteria.
    • Components of the lac operon:
    • Regulatory region: Contains the lacI gene coding for the lac repressor which binds to the operator.
    • Structural genes: Includes lacZ (beta-galactosidase), lacY (lactose permease), and lacA (transacetylase).
    • Functionality:
    • Lac operon is responsible for lactose metabolism.
    • It operates as a polycistronic unit, producing a single mRNA that codes for multiple proteins.
  • Regulation Mechanisms
    • Default state: Lac operon is usually off due to the repressor binding to the operator.
    • Presence of lactose: When lactose is present, it binds to the repressor, changing its shape and allowing RNA polymerase to transcribe the operon, leading to the production of enzymes for lactose metabolism.
    • Absence of lactose: In the absence of lactose, the repressor remains bound, preventing transcription.
    • Constitutive mutations:
    • I- (mutant repressor) leads to constitutive expression of the operon regardless of lactose presence.
  • Glucose Impact on Lac Operon
    • Effect of glucose:
    • When glucose is present, the lac operon is inhibited due to catabolite repression.
    • High glucose levels lead to low cAMP, preventing CAP (Catabolite Activator Protein) from facilitating RNA polymerase binding.
    • Maximum transcription: Achievable with high lactose and low glucose conditions.
    • Scavenging mechanism: In the presence of glucose, low levels of transcription may still occur with lactose present.
  • Human Lactose Metabolism
    • Genetic variations lead to differences in lactose tolerance (lactase persistence) among populations.
    • Lactase persistence refers to continued production of lactase in adulthood, a result of mutations primarily in the MCM6 gene, influencing lactase gene expression.
    • Genetic adaptations: Mutations that favor lactose digestion were historically selected for in pastoralist societies.
  • Tryptophan (Trp) Operon
    • The trp operon functions differently from the lac operon.
    • Default state: The trp operon is typically on, allowing tryptophan biosynthesis.
    • Repression: Activated when intracellular tryptophan levels are high, reducing further production.
    • Attenuation: Involves a leader sequence and a regulator that can form different secondary structures in RNA, depending on charged tRNA availability, determining whether transcription continues or terminates.
  • Important Terms and Concepts
    • Cis vs. Trans:
    • Cis elements are those that are physically connected (like promoters).
    • Trans elements can act at a distance (such as diffusible proteins like repressors or activators).
    • Polycistronic mRNA: Allows for coordinated expression of genes with related functions.
    • Scavenging: Refers to low-level expression in absence of a direct signal, ensuring readiness for sudden availability of the substrate.