Gene Structure 5

Question 1

What is an overlapping gene?

Answer 1

Adjacent genes located on either the same or the opposite DNA strand, sharing one or more nucleotides of coding sequence. Genes can also overlap regulatory regions.

Question 2

What do overlapping genes allow?

Answer 2

Multiple proteins encoded from the same sequence, coding regions to be on both strands and for co-regulation of related proteins.

Question 3

Where were overlapping genes first seen?

Answer 3

ssDNA in phage genomes.

Question 4

Where are overlapping genes found?

Answer 4

In mitochondria, microbes and eukaryotes. Seen in 10% of human genes.

Question 5

Give 3 types of overlapping gene.

Answer 5

Same strand, different strand and partial/terminal overlaps.

Question 6

Describe a same strand overlap.

Answer 6

Unidirectional. The 3’end of one gene overlaps with the 5’ end of another gene on the same strand. Genes may be regulated by common promoter.

Question 7

Where are same strand overlaps commonly found?

Answer 7

In bacteria, for example E.coli has 586 same strand overlap gene pairs.

Question 8

What are the two types of different strand overlap?

Answer 8

Convergent and divergent.

Question 9

Describe a convergent different strand overlap.

Answer 9

Overlap of the 3’ ends of two genes on different strands, Overlap contains polyadenylation sites.

Question 10

Where are convergent different strand overlaps commonly found?

Answer 10

In drosophila

Question 11

Describe a divergent different strand overlap.

Answer 11

Overlap of the 5’ ends of two genes on opposite strands,. Transcription of both genes may be controlled by a bidirectional promoter.

Question 12

Describe a partial/terminal overlap.

Answer 12

Involves a small 5’/3’ overlap (often 1bp) of coding sequence. Terminator site for one gene overlaps with the initiator site of another. Common in prokaryotes.

Question 13

Give an example of partial/terminal overlap found in bacteria.

Answer 13

1 base overlap between TrpE and TrpD. Shine-Dalgarno of TrpA within TrpB. Allows proteins to be synthesised in equal ratios. Translation coupling is dependent on partial overlaps.

Question 14

What is the result of in phase overlaps?

Answer 14

Coincident reading frames.

Question 15

Where are in phase overlaps commonly found?

Answer 15

In bacteria and viruses.

Question 16

What are the two types of in phase overlaps?

Answer 16

Different initiation or different termination.

Question 17

Describe in phase overlaps with different initiation sites.

Answer 17

Alternative transcription start sites, can have the promoter for one gene within the coding region on an adjacent gene. Genes share the same terminator- proteins have dissimilar N termini and identical C termini.

Question 18

Give an example of an in phase overlap with different initiation sites.

Answer 18

Aspartokinase in Thermus flavus-initiation differs, askB subunit overlaps with the 3’end of the askA subunit.

Question 19

Describe in phase overlaps with different termination sites.

Answer 19

Genes have the same initiator codon but termination occurs at distinct codons in each gene. Proteins have dissimilar C termini and identical N termini.

Question 20

Give an example of an in phase overlap with different termination sites.

Answer 20

Pili gene C53 in E.coli- termination differs, produces 5 different polypeptides due to overlap.

Question 21

What results from out of phase overlapping genes?

Answer 21

Overlapped genes are in different ORFs to one another. Short overlaps are often in phase 2 and large overlaps are often in phase 1.

Question 22

Where are out of phase overlaps commonly seen?

Answer 22

In prokaryotes and phages.

Question 23

Give an example of an out of phase overlap.

Answer 23

Mouse lnk4a/Arf- alternative first exons (1α and 1β) transcribed from different promoters. Both spliced to same acceptor site in exon 2, which gets translated in alternative frames. Produces two different tumour suppressor proteins.

Question 24

What is ribosomal frameshifting?

Answer 24

The ribosome pauses on the mRNA and shifts before continuing- usually by 1 base. Codons read after the shift are in a different reading frame.

Question 25

What is required in mRNA for a site specific programmed ribosomal frameshift to occur?

Answer 25

Slippery sequence, spacer sequence and downstream stimulatory structure.

Question 26

What is the role of the downstream stimulatory structure?

Answer 26

Forms pseudoknots/kissing stem loops. Acts as an energetic barrier, aiding positioning of the ribosome over the slippery sequence so that a frameshift can occur.

Question 27

What are the 3 models for ribosome slippage during translation elongation?

Answer 27

3 tRNAs model, 9A model and the cotranslocation model.

Question 28

Describe the 3 tRNAs model for ribosome slippage.

Answer 28

Slippage occurs before peptidyl transfer, whilst the aa-tRNA is still in the A site. Peptidyl transfer is blocked by the pseudoknot, ribosome pauses and shifts -1.

Question 29

Describe the 9A model for ribosome slippage..

Answer 29

Pseudoknot resists 5’ mRNA movement- tension caused by 9A movement of the anticodon loop. This causes +1 frameshift. Occurs before aa-tRNA binds the A site.

Question 30

Describe the cotranslocation model for ribosome slippage.

Answer 30

Occurs after peptidyltransfer. tRNA moves to E site and aa-tRNA moves to the A site. Downstream element of mRNA resists movement. EF-Tu causes the P site to be deformed, breaking anticodon-codon interaction. This causes the ribosome to pause and shift.

Question 31

Give an example of a -1 PRF.

Answer 31

dnaX in Salmonella typhumerium/ E.coli - codes for DNA Pol III. PRSF 2/3 way into transcript length. Termination codon after frameshift- proteins produced from frameshift are shorter. Can also have -4/+2 frameshifts.

Question 32

Give an example of a +1 PRF.

Answer 32

OAZ1 in Saccharomyces cerevisae. Ornithine decarboxylase (ODC) produces polyamines. OAZ stimulates ubiquitin-dependent degradation of ODC. Polyamines stabilise pseudoknot, increasing +1 frameshifts and and OAZ production, as a high enough conc. of polyamines have been produced, and ODC is no longer needed- negative feedback.

Question 33

Give the advantages of overlapping genes in bacteria and viruses.

Answer 33

Allows genome compression which results in faster replication and lower mutation rates. Increases protein diversity and genome complexity. Can allow coordinated control- different expression levels of different proteins relative to each other.

Question 34

Why is genome compression particularly important for viruses?

Answer 34

Viral genome is limited by the capsid size.

Question 35

Why are overlapping genes more conserved than non-overlapping genes?

Answer 35

Any mutations could affect the functions of both gene products.