Overlapping Genes

Question 1

Overlapping Genes

Answer 1

• 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

Question 2

Same strand overlap

Answer 2

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

Question 3

Different strand overlap

Answer 3

• convergent: 3’ end overlap

- divergent: 5’ end overlap

Question 4

In phase overlaps

Answer 4

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

Question 5

Thermus flavus

Answer 5

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

Question 6

Out of Phase Overlaps

Answer 6

• 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

Question 7

Partial Overlap

Answer 7

• 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

Question 8

Translational Recoding

Answer 8

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

Question 9

Ribosomal Frameshift

Answer 9

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

Question 10

-1 Frameshift

Answer 10

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

Question 11

+1 Frameshift

Answer 11

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

Question 12

HIV Virus

Answer 12

• 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

Question 13

Advantages

Answer 13

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

Question 14

Disadvantages

Answer 14

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

Question 15

Eukaryotes vs Prokaryotes

Answer 15

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

Question 16

Antisense Transcription

Answer 16

• 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