Overlapping Genes Flashcards

1
Q

Overlapping Genes

A
  • adjacent genes located on either DNA strand sharing one or more nucleotides in the coding sequence
  • one gene considered reference gene
  • other genes either in or out of phase
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2
Q

Same strand overlap

A
  • uni directional
  • 3’ end of one gene overlaps with 5’ end of another
  • regulated by common promoter
  • expressed at the same time
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3
Q

Different strand overlap

A
  • convergent: 3’ end overlap

- divergent: 5’ end overlap

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4
Q

In phase overlaps

A

Initiation diff.

  • alternative translation start site
  • new internal promoter formation
  • identical c and different n terminals

Termination diff.

  • same initiator codon
  • termination at distinct codons
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5
Q

Thermus flavus

A
  • aspartokinase has A/B genes
  • askA: a subunit
  • askB contains B subunit at 3’ end of askA
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6
Q

Out of Phase Overlaps

A
  • non identical reading frames
  • hard to get large overlaps due to higher percentage of stop codons
    eg. mouse tumor suppressor gene
  • link4a/Arf locus
  • alternative first exons transcribed from different promoters
  • spliced to same acceptor site and translated in different frames
  • both products key tumor suppressors
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7
Q

Partial Overlap

A
  • small overlaps of 5’/3’ end
  • terminator site of 1 gene overlaps with initiator of another
    eg. Tryptophan operon
  • trpE-D have one base overlap
  • proteins synthesize in equimolar ratios
  • couples translation
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8
Q

Translational Recoding

A
  • ribosomes directed to utilise alternative start sites, bypass termination codons, or programmed shift of reading frame
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9
Q

Ribosomal Frameshift

A
  • ribosome pauses and moves one nucleotide before continuing
  • not all ribosomes shift
  • depends on mRNA regulatory structure and sequence
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10
Q

-1 Frameshift

A
  1. slippery sequence: 7 nucleotides
  2. spacer sequence: 12 nucleotides
  3. downstream stimulatory structure: pseudoknots/stem loops creating an energetic barrier that must be unfolded
    - aids positioning over slippery site/pause of ribosome
    - ribosome encounters frameshifting signal
    - ribosome pauses at pseudoknot
    - slips back one base
    - unwinds pseudoknot and continues translating in -1 frame
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11
Q

+1 Frameshift

A

eg. S. cerevisiae
- OAZ1 gene
- ODC produces polyamines
- OAZ stimulates ubiquitin independent degradation of ODC
- polyamines stabilise pseudoknot causing +1 frameshift
- maintains polyamine levels at suitable levels as OCD increases them, producing OAZ that degrades ODC and stops their production

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12
Q

HIV Virus

A
  • 1 PRF example
  • Gag produced as precursor protein
  • GagPol polyprotein contains viral enzymes protease, reverse transcriptase, and integrase in expressed at 1% of the Gag level due to -1 frameshift
  • disruption causes inefficient assembly
  • drug target to combat HIV
  • stem loop stabilise to give more GagPol making it less efficient for virus to assemble
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13
Q

Advantages

A
  1. genome compression
  2. PRF increases diversity
  3. coordinated control
  4. might mitigate detrimental effects of mutation
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14
Q

Disadvantages

A
  • overlapping genes may be subject to evolutionary constraint
  • one gene adaptation is constrained by other overlapping genes
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15
Q

Eukaryotes vs Prokaryotes

A

Eukaryotes

  • overlap can be in introns
  • more abundant overlaps
  • less divergent different strand overlaps (5’ end important for regulation/localisation)

Prokaryotes

  • exon overlapping common
  • unidirectional overlap common
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16
Q

Antisense Transcription

A
  • impacts initiation, elongation, post-transcription
  • sense and antisense pairs as self regulatory circuits
    Initiation
  • long antisense transcribed, binding to PRC2 complex and methylating DNA to stop transcription of sense gene
    Elongation
  • RNA pol collision
    Post
  • can stop degradation of RNA by miRNA
    eg. BACE1: high levels in Alzheimers patients