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Eukaryotic Gene Control

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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  1. Eukaryotic Gene Control

  2. 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.

  3. 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

  4. 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

  5. Deacetylation (removing of acetyl groups) creates a tighter, super coiled DNA structure • Difficult for transcription to proceed

  6. DNA demethylation: • Inactive Mammalian X chromosomes (Barr bodies): • Highly methylated (-CH3) bases, particularly cytosine • Removing of methyl groups can activate these genes

  7. 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)

  8. 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

  9. 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

  10. Genome Evolution: • What drives genome evolution?

  11. 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

  12. 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

  13. 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

  14. 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

  15. Rearrangements of parts of genes: • Exon duplication and shuffling: • Presence of introns responsible for exon shuffling and duplication? • Leads to new proteins

  16. 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

  17. 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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