The evolving genome

Question 1

Does genome size correlate with gene density?

Answer 1

No - eg. prokaryotes densely packed with genes and few or no introna whereas metazoa less gene rich but with many introns/repetitive elements

Question 2

What is the genome composition in humans like?

Answer 2

1.5-4.5% genes

Rest is mainly repetitive with tandemly repeated DNA (satellite DNA) and interspersed genome-wide repeats

Question 3

What are the three types of tandemly repeated DNA?

Answer 3

Microsatellites - less than 10 nucleotides
Minisatellites - 10-60 nucleotides
Macrosatellites - 100-1000 nucleotides

Question 4

What is the function of tandemly-repeated DNA?

Answer 4

No apparent function
Microsatellites correlate with some diseases eg. microsatellite instability linked to colorectal cancer as affects DNA mismatch repair

Question 5

What are the different mechanisms of origin for short and long tandem DNA repeats?

Answer 5

Short (di or tri-nucleotides) - random changes in non-functional sequences
Longer - duplicate by unequal crossing over or replication errors

Question 6

In what two areas can repetitive DNA be functional?

Answer 6

Centromeres - repetitive DNA found in and around centromere, they are sites of interaction for spindle fibres (which separate chromosomes)
Telomeres - have repeated TTAGGG which is synthesised by telomerase, it caps and protects ends of chromosomes and linked to aging

Question 7

What are interspersed repeats?

Answer 7

Repeat sequences dispersed throughout genome, derived from transposable elements (which are mobile DNA elements that can move around genome, most seen as junk as only few ‘active)

Question 8

What is the difference between tandem repeat DNA and interspersed repeats?

Answer 8

In tandem the repeat sequences come right after one another, in interspersed they are not adjacent

Question 9

What are the two major classes of transposable elements?

Answer 9

Retrotransposons (class 1) 
DNA transposons (class 2)

Question 10

What are three types of retrotransposons?

Answer 10

LINES
SINES
LTR
(copy and paste themselves into different genomic locations by converting RNA back into DNA through reverse transcriptase)

Question 11

What are LINES? (the retrotransposons)

Answer 11

Long interspersed elements derived from selfish DNA sequence encoding reverse transcriptase
Each line approx. 7000 base pairs long
LINE1 still active and LINE2/LINE3 relics

Question 12

What are SINES? (the retrotransposons)

Answer 12

Short interspersed elements that do not encode their own reverse transcriptase
They disperse via an RNA intermediate that undergoes reverse transcriptase (relying on reverse transcriptase products from elsewhere)

Question 13

What are LTRs? (long terminal repeats, retrotransposons)

Answer 13

Pair of identical DNA sequences that occur in eukaryotic genomes and form a retrotransposon
No ‘Env’ gene so cannot be packaged to leave cell but cDNA can be inserted elsewhere

Question 14

What are DNA transposons?

Answer 14

DNA sequences that can move and integrate into different regions of genome
They move through a DNA intermediate and can be autonomous or non-autonomous

Question 15

What differentiates autonomous and non-autonomous DNA transposons?

Answer 15

Autonomous - encodes for transposase (which excises transposable element from genome and catalyses reinsertions at another site)
Nonautonomous - require usage of transposase gene from another transposable element

Question 16

What is the C-value paradox?

Answer 16

The idea that the amount of DNA in a haploid genome (the 1C value) does not correlate with the complexity of an organism
Genome size usually correlates to amount of transposable element sequences as large genomes typically have many of these

Question 17

How do transposable elements increase copy number without harming host?

Answer 17

Target new insertions into ‘safe havens’ - regions of the genome where there are very few genes

Question 18

In what ways can duplication occur to assist genome evolution?

Answer 18

Replication slippage
Unequal crossing over
Transposition

Question 19

How does replication slippage cause duplication?

Answer 19

During replication of repetitive sequences the growing strand may slip, causing the polymerase to move back and synthesise the region a second time which creates an insertion

Question 20

How does unequal crossing over cause duplication?

Answer 20

Homologous elements located close to each other catalyse unequal crossing over so genes between these elements may be duplicated
This can give rise to multigene families of related genes that start off clustered together

Question 21

What are multigene families?

Answer 21

Set of related proteins encoded by a set of similar genes

They can be located on the same chromosome (tandem gene families) or different chromosomes (dispersed gene families)

Question 22

What are the four hierarchal levels of gene duplication?

Answer 22

• Exons duplicate/shuffle
• Entire genes duplicate and create multigene families
• Gene families duplicate to produce gene superfamilies
• Entire genome duplicates, doubling the number of gene/gene family copies

Question 23

Gene duplication can lead to pseudogenes - what are these?

Answer 23

Non-functional DNA segments that resemble functional genes

Question 24

What is an example of exon shuffling?

Answer 24

Tissue plasminogen activator (TPA) - a serine protease responsible for the breakdown of blood clots
Evolved by exon shuffling from plasminogen, fibronectin and epidermal growth factor