Gene Expression and Control

Mutations and SNPs

• Grandma's DNA mutation was the origin.
• Humans have dealt with DNA changes for thousands/millions of years.
• Mutations are old and cause benign differences.
• SNPs (single nucleotide polymorphisms) are single base pair changes within a population.
• SNPs differentiate individuals.
• Ancestry tests look for SNPs or patterns of SNPs.
• Many SNPs have little to no biological function.

Control of Gene Expression

• Each cell contains all genes but doesn't express them all.
• Example: Lung cells don't produce hair protein typically.
• Dermoid cysts are tumors where gene expression is disrupted, often in the ovary.
• Ovarian cells start producing incorrect proteins, leading to cyst formation.
• Dermoid cysts: Inappropriate gene expression.
• A dermoid cyst can contain hair, teeth, and other tissues.

Prokaryotic vs. Eukaryotic Gene Expression

• Gene expression control differs between prokaryotes and eukaryotes.
• Prokaryotic gene expression is controlled by operons.

Operons

• Operon: Multiple genes controlled by one promoter and one regulatory element involved in same biological process.
• E. coli in the gut consume leftover food, aiding natural flora.
• E. coli can consume lactose, a disaccharide of glucose and galactose.
• Lactose is milk sugar.
• Enzyme lactase breaks the bond in lactose.
• Most humans stop producing lactase after weaning.
• Undigested lactose feeds gut bacteria, causing lactose intolerance.
• Lactose intolerance: Bacteria consume lactose, produce gas, causing digestive distress.

Lactose Intolerance and Solutions

• Lactose intolerance occurs due to reduced lactase production after periods without milk consumption.
• Lactase supplements can aid lactose digestion by breaking it down before it reaches bacteria.
• Babies consume bacteria from mom when feeding.
• The smell is from the bacteria.
• Dairy allergies involve immune response to milk proteins, unlike lactose intolerance.
• Lactose intolerance is not life-threatening, unlike dairy allergies.

Regulation of Lactose Metabolism in Bacteria

• Bacteria produce lactase to digest lactose.
• Without lactose, bacteria conserve energy by not producing lactase.
• Bacteria can turn on/off lactase production based on environment.
• Lactose absent: Bacteria doesn't make proteins.
• Lactose present: Bacteria makes lactase and transporter.
• The lac operon controls lactose metabolism.

The Lac Operon

• The lac operon is a regulatory element that controls a set of genes involves in the metabolizing of lactose.
• Promoter: Where RNA polymerase binds to start transcription.
• Three genes downstream of promoter:
  • lac y
  • lac z
  • lac a
• LacZ makes lactase (hydrolyzes lactose).
• LacY makes lactose transporter protein.
  • LacA function is unknown.
• Operator: Specific region in the promoter, the control element.
• LacR gene: Located elsewhere, constitutively expressed (always on).
• LacR protein: Lac repressor, binds to operator.
• Lac repressor physically blocks RNA polymerase from transcribing genes, turning operon off when no lactose is present.

How Lactose Affects the Lac Operon

• Lactose enters bacteria, binds to allosteric site on lac repressor, changing its shape.
• Altered repressor detaches from operator.
• RNA polymerase can now transcribe genes.
• Lac operon is an inducible operon i.e. the lactose.

Tryptophan and the trp Operon

• Bacteria can synthesize tryptophan.
• If no tryptophan available, bacteria produce tryptophan-producing enzymes.
• If tryptophan is present, bacteria don't need to make it.

Repressible Operon (trp Operon)

• The trp operon functions oppositely to the lac operon.
• Components:
  • Promoter (with operator)
  • Genes for tryptophan-producing enzymes (trpA, trpB, trpC, trpD, trpE, etc.)
  • trpR gene (codes for TrpR repressor protein)
• Without tryptophan, the TrpR repressor is inactive.
• RNA polymerase binds to promoter, transcribes genes.
• Genes are on, operator is on, enzymes are produced.

Regulation of the trp Operon by Tryptophan

• Tryptophan from environment binds to allosteric site on TrpR repressor, activating it.
• Activated repressor binds to operator, blocking RNA polymerase.
• Transcription stops, and tryptophan-producing enzymes aren't made.
• The Tryptophan operon is repressible; adding the agent turns it off.

Deactivation of Operators

• Both tryptophan and lactose are constantly being turned over.
• Bacteria constantly use tryptophan to build it's own proteins.
• Bacteria dividing all the time uses tryptophan.
• When the concentration of tryptophan gets low, repressor is less adhere.
• For the lactose once the bacteria has eaten all the lactose concentration gets low enough that the lactose leaves the repressor.