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Eukaryotic Gene Control. Developmental pathways of multicellular organisms:. All cells of a multicellular organism start with the same complement of DNA Multicellular organisms have developmental pathways from zygote to adult

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developmental pathways of multicellular organisms
Developmental pathways of multicellular organisms:
  • All cells of a multicellular organism start with the same complement of DNA
  • Multicellular organisms have developmental pathways from zygote to adult
    • Developmental sequences are predominately determined and programmed by differential gene expression.
differential gene expression on many levels
Differential gene expression on many levels:
  • 1. Pre Transcription
    • Chromatin
  • 2. Transcription
  • 2. Post Transcription
    • RNA processing, transport to cytoplasm, degradation of mRNA
  • 3. Translation
  • 4. Post Translation
    • Cleavage and chemical modification, degradation of protein
examples pre transcription
Examples: Pre-transcription
  • Histone Acetylation of chromatin:
    • Histones = group of 5 proteins associated with the coiling of DNA (positively charged regions)
    • Histone acetylation: acetyl group (-COCH3
      • Attached to positively charged regions
      • Neutralizes the histones
      • Causes DNA to become loser
      • Transcription proteins can access the DNA with greater ease
slide5

Deacetylation (removing of acetyl groups) creates a tighter, super coiled DNA structure

    • Difficult for transcription to proceed
dna demethylation
DNA demethylation:
  • Inactive Mammalian X chromosomes (Barr bodies):
    • Highly methylated (-CH3) bases, particularly cytosine
    • Removing of methyl groups can activate these genes
regulation of transcription initiation
Regulation of Transcription Initiation:
  • Typical Eukaryotic Gene
    • distal control elements(enhancers)
    • proximal control elements
    • promoter
    • RNA polymerase binding sequence
    • exons(coding regions)
    • intron(non coding regions)
transcription factors
Transcription Factors:
  • Proteins that assist RNA polymerase in initiating transcription
    • Transcription of particular genes at the appropriate time and place depends on the interaction of specific transcription factors
  • Example:
    • Activator: binds to an enhancer and stimulates transcription of a gene
    • Repressors: inhibit expression of a particular gene
post transcriptional regulation
Post Transcriptional Regulation:
  • Alternative RNA splicing:
    • Primary transcript produces different mRNA molecules
  • mRNA degradation:
    • Poly A tail and methyl G cap resist mRNA degradation in the cytoplasm until translation has occurred
    • Life span of mRA determines the pattern of protein synthesis in a cell.
    • Example: mRNA’s for the hemoglobin polypeptide are long lived and can translate repeatedly for red blood cells
genome evolution
Genome Evolution:
  • What drives genome evolution?
evolution of genes with novel functions
Evolution of genes with novel functions:
  • Polyploidy – extra set of chromosomes
    • One copy maintains original function
    • duplicate sets accumulate mutations and diverges from other set
      • Could develop novel phenotypes
    • Common in plants, not so much in mammals
    • Antifreeze gene in fish
duplication and divergence of dna segments
Duplication and divergence of DNA segments:
  • Genes can become duplicated from errors during meiosis I
    • Unequal crossing over (prophase I)
    • Results in deleted or duplicated regions of DNA
evolution of genes with related functions
Evolution of Genes with Related Functions:
  • Example of how a duplication can lead to gene evolution:
  • α- globin and β- globin gene families
    • Shared a common ancestral globin gene
    • Duplicated and Diverged about 450- 500 million years ago
    • Divergence continues as duplications add up within the gene families
    • Other families have emerged from the same ancestral globin gene
evolution of genes with novel function
Evolution of Genes with novel function:
  • Lysozymes and α- lactalbumin- very similar amino acid sequence ands three dimensional structure
    • Both found in mammals
    • Only lysozymes found in birds
rearrangements of parts of genes
Rearrangements of parts of genes:
  • Exon duplication and shuffling:
    • Presence of introns responsible for exon shuffling and duplication?
    • Leads to new proteins
exon duplication and deletion within a particular gene
Exon duplication and deletion within a particular gene:
  • Coding for a second copy of the protein
    • Could alter protein structure
    • Example: Collagen has a highly repetitive amino acid sequence which reflects the repetitive exons in the collagen gene
mixing and matching exons
Mixing and Matching Exons:
  • Could lead to new proteins with novel combinations and functions
  • Example: TPA- tissue plasminogen activator
    • Extracellular protein that limits blood clotting
    • Had four domains of three types
      • Each domain is coded by an exon(one codes twice)
    • Result of several instances of exon shuffling
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