Regulation and Mutations Notes

Regulation and Mutations

Learning Objectives

  • Regulation of Gene Expression in Prokaryotes
  • Regulation of Gene Expression in Eukaryotes
  • Gene Expression Helps Cells Specialize
  • Mutations Overview

Gene Expression and Phenotype

  • An organism's phenotype is determined by the genes expressed and their levels.
  • Regulation of gene expression is crucial for an organism's phenotype.
  • Genes are regulated by regulatory proteins interacting with regulatory sequences.
  • Mutations can affect gene expression.

Regulation of Gene Expression in Prokaryotes

  • Prokaryotes use operons to regulate gene expression.
  • An operon is a cluster of genes with a common function under a common promoter.
    • Regulatory sequences
    • Genes for regulatory proteins
    • Genes for structural proteins
  • Promoters: Binding sites for RNA polymerase.
  • Operators: Binding sites for repressor proteins.
  • Structural genes: Coding sequences for proteins that perform the operon's function.
  • Two types of prokaryotic operons:
    • Inducible operons
    • Repressible operons

Inducible Operons

  • Usually have a catabolic function (digesting molecules).
  • Turned off unless the appropriate inducer molecule is present.
  • Repressor protein binds to the operator sequence, blocking transcription.
  • Inducer molecule binds to the repressor protein, changing its shape and preventing it from binding to the operator.
  • Example: lac operon
    • Function: produce proteins to digest lactose.
    • lac repressor protein binds to the operator when no lactose is present.
    • Lactose acts as the inducer molecule.
Positive Regulation of lac Operon
  • cAMP and CAP interaction.
  • Low glucose levels increase cAMP levels.
  • cAMP binds to CAP, stimulating CAP to bind near the promoter.
  • Increases RNA polymerase affinity, stimulating transcription.

Repressible Operons

  • Usually have an anabolic function (synthesizing molecules).
  • Turned on unless the product is abundant.
  • Example: trp operon
    • Function: produce enzymes to synthesize tryptophan.
    • Tryptophan acts as a corepressor.
    • The trp repressor protein must be bound to tryptophan to bind to the operator.
    • If no tryptophan is present, the trp repressor will not bind, and RNA polymerase can transcribe the operon.

Key Differences Between Inducible and Repressible Operons

  • Function (catabolic vs. anabolic)
  • Whether the repressor protein requires a corepressor to bind to the operator

Regulation of Gene Expression in Eukaryotes

  • Eukaryotes use interactions between regulatory sequences and regulatory proteins.
    • Promoters: Binding sites for RNA polymerase.
    • Regulatory switches
      • Enhancers: Activator proteins or transcription factors bind.
      • Silencers: Repressor proteins bind.
    • Regulatory proteins
      • Repressors: Turn off gene expression by binding to regulatory switches.
      • Activators: Upregulate gene expression by binding to regulatory switches.
      • Transcription factors: Help RNA polymerase bind to the promoter and start transcription.
      • Mediators: Connect other regulatory proteins.

Epigenetic Changes

  • Reversible modifications to DNA nucleotides, such as methylation (adding a methyl group).
    • Methylated nucleotides are less likely to be transcribed.
  • Histone proteins can be modified by acetylation (adding acetyl groups).
    • Acetylation makes DNA more loosely wound, accessible, and likely to be expressed.

Chromatin Structure

  • Euchromatin: Loosely wound DNA, more accessible to RNA polymerase, more gene expression.
  • Heterochromatin: Tightly wound DNA, less accessible to RNA polymerase, reduced gene expression.

Small Interfering RNA (siRNA)

  • siRNA binds to complementary mRNA molecules, forming double-stranded RNA (dRNA).
  • Enzymes destroy dRNA, reducing gene expression.

Gene Expression and Cell Specialization

  • Differential gene expression: different genes are expressed in different cells.
  • Influences cell function and organism phenotype.
  • Different tissue types express different genes, leading to cell differentiation.
  • Timing of transcription factor expression is critical.
  • Hox genes: Code for transcription factors; mutations or mis-expression can cause body plan errors.

Mutations

  • Changes in the genetic material of an organism.
  • Can change the organism's phenotype.
  • Provide genetic variation in populations.
  • Can be beneficial, harmful, or have no effect, depending on the environment.
  • Caused by environmental factors, errors in DNA replication, or DNA repair mechanisms.

Aneuploidy

  • Failure of homologous chromosomes to separate during meiosis.
  • Results in an atypical number of chromosomes.
  • Examples
    • Down Syndrome (Trisomy 21): Individuals have three copies of chromosome 21.
    • Klinefelter syndrome: Individuals have three sex chromosomes: two X and one Y.

Horizontal Transmission of Genetic Information

  • Transformation: Uptake of naked foreign DNA.
  • Transduction: DNA transfer by viruses.
  • Conjugation: DNA transfer through cell-to-cell contact via a pilus.
  • Transposition: Movement of DNA between chromosomes or within a chromosome ("jumping genes").