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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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Eukaryotic Gene Control

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Eukaryotic gene control

Eukaryotic Gene Control

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

Eukaryotic gene control

  • 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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