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Genetics, Lecture 1 - Coggle Diagram

- - - - Activties of the same cell
      - Cell types
    - - initiate different patterns of gene expression. They begin as groups of cells which are:
        
        pluripotent
        
        Multipotent
        
        Fully differentiated cells
        
        Totipotent: Can differentiate into any cell type
  - - - Transcriptional
        
        RNA transcription
        
        sigma subunit dissociates from the promoter, UNWINDING of strands and copying of DNA to RNA
        
        Elongation phase
        
        RNAp recognizes specific seuquences which terminate RNA synthesis
        
        Chain termination
        
        Cause hairpins to form in the growing RNA molecule
        
        instrinsic termination signals
        
        Rho (protein) recognizes certain sequence elements, binds to RNAp, cuases it to fall off DNA and release RNA
        
        Rho-dependent termination
        
        Transcriptional repressors
        
        Sit on or close to promoter regions of DNA, preventing RNA polymerase or initiator proteins from starting transcription - turning off gene
      - Post-transcriptional
        
        Stability or composition of RNA
      - Translational
        
        Translation of mRNAs into protein
      - Post-translational
        
        Protein function or activity state
    - - Binding of RNApolymerase to promoter region
      - Specific DNA sequences found close to transcription start sites of most genes
      - Prokaryotes
        
        1 RNA polymerase utilized
      - Eukaryotes
        
        3 RNA polymerase complexes
      - Bacteria
        
        same basic organization
        
        TATA BOX AND ttgacat upstream of the gene
        
        Sigma subunit
        
        positions polymerase at correct position to initiate transcription
  - - - controlled by Lac repressor protein
      - Regulates expression of genes involved in lactose utilization in bacteria
      - Jacob and Monod discovered that beta-galactosidase is induced 10,000 fold over normal expression levels when bacteria were grown on lactose
      - growth on lactose depends on
        
        Beta-galactosidase
        
        Permease
        
        Thiogalactoside transacetylase
        
        Each encoded by different gene but
        
        3 genes tightly linked on chromosome
        
        All were induced coordinately
        
        Ratio of lac Z:A:Y proteins remained constant
      - lacI encodes a repressor which switches off whole operon without lactose
- - - - Spliced out of mRNA after synthesis
      - introns evolve rapidly
        
        mammalian genes contain more intron than exon sequence
      - introns lost from prokaryotes
    - - Recognises junctions between introns and exons
      - excises the introns to produce fully spliced mRNA molecule
  - - - Two different proteins made in thyroid cells vs neurons
  - - - 1 for mRNA
        
        E exit site
      - two for tRNA
        
        A for aminoacyl site
        
        P for peptidyl site
        
        tRNA carry amino acids to mRNA template
    - - tRNA associated with specific amino acids
      - tail end has acceptor stem that can bind
      - Head has 3 nucleotides which form anticodon
      - Stages of translation
        
        Initiation
        
        mRNA molecule binds to small subunit
        
        Recognises 5' cap
        
        Shine Dalgarno sequence
        
        Initiated by AUG codon
        
        Start codon enters P site
        
        second codon enters A site
        
        anticodon carrying methionine base pairs with start codon
        
        Forms peptide bond
        
        Elongation
        
        P site binds tRNAs carrying amino acids
        
        E site releates dissociated tRNAs
        
        Ratchet-like conformational change
        
        Energy for each peptide bond formation derived from GTP hydrolosis
        
        Termination
        
        Translation process repeats until 1 of 3 codons eneters A site of ribosome
        
        After final peptide bond is created , protein chain moves to cytoplasm
  - - - Contains ribosomal RNA and ribosomal proteins
      - Translate information together
    - - Differ from prokaryotes
        
        Large 60S
        
        Small 40S
        
        80S ribosome
      - bound to 46 proteins
    - - 70S ribosomes.
        
        1 large 50S
        
        one small 30S
      - Bound to 21 different Ribosomal proteins
      - Bound to 31 proteins
- - - - General
        
        eg. TFIID
        
        Contains a TATA box-binding protein (TBP)
        
        Large beta-sheet forms a saddle-shaped structure which sits astride the DNA
        
        Binding of TBP to TATA box induces dramatic distortion in DNA
      - Gene-specific
        
        share common DNA binding domains
        
        4 motifs
        
        Helix-loop-helix motif
        
        leucine zipper
        
        High mobility group-box
        
        Zinc finger motif
        
        all sightly different solutions to recognise specific DNA sequences by TFs
        
        Most contain alpha-helix which inserts into major groove of DNA
        
        forms non-covalent interactions once it recognises side chains
        
        Affinity of TFs for their specific DNA sequence ranks is one of the highest seen in biological systems
        
        100s exist
    - - Need for specific and general transcription factors
      - physical inaccessibility of gene promoters
    - - Bind to enhancer sequences
      - Chromatin looping brings the region close to the TATA box
  - - - Uncouples polymerase from some of the TFs, allowing movement
- - - - methylation
      - Acetylation
        
        Leads to a more open chromatin state
        
        Neutralising negative charges loosens contact with DNA
        
        Carried out by histone acetyltransferases (enzymes)
        
        Reversible through histone deacetyltransferases
    - - Some use polycomb proteins that repress expression of genes
      - do this by staying associated with DNA
  - - - Histone octamers
  - - - Not random, mainly in GC-rich regions (CpG islands
      - Most methylated cytosines found here
      - within symmetrical sequences, like CCGG
      - Unmethylated CpG islands found near active gene promoters
    - - By interfering with recognition of DNA binding sites by TFs
      - Attracts transcriptional repressors to certain sites
    - - Not the initial event
      - Inhibits transcription by
        
        Interfering with recognition of DNA-binding sites by TFs
        
        Attracting transcriptional repressors to certain sites
    - - Enzymes (demethylases) can add and remove methyl groups to DNA
      - demethylation of inherited methyl groups in zygote
    - - Acts preferentially on CG sequences which are already methylated
- - - - translation into protein
    - - RNAs translated into cytoplasm
        
        Thus needs 5' end of RNA as well as 3'
      - Modifications
        
        stabilize mRNA
        
        Facilitates export from the nucleus
        
        Undergo splicing by small nuclear RNAs
- - - - Many genes encode RNA molecules which do not translate into protein