Transposons
Presenter: Dr. Karthikeyan Moderator: Dr. Sarita Agarwal
Outline
Discovery
Types
Mechanism of transposition
Role • Evolution•Gene therapy
Selfish DNA
Jumping genes
Genomic parasite
• Some transposable elements are introns
• Not all introns are TE.
•Transposable elements are DNA sequences that move from one location on the genome to another.
Why are these kernels spotted ?
Somatic Excision of Ds from C
Fig. 23.9
SectoringWild type
Ds is derived from Ac by internal deletions
Ds is not autonomous, requires Ac to move
Ac encodes a protein that promotes movement - Transposase
1942• Mcclintock’s discovery
1950 • TEs were discovered in fruit fly
1960 • E. coli
1970•Human genome
Thanks to transposons
Before Mcclintock
genes have fixed location
After Mcclintock
genes can move
After 40 long years
Types of Transposons
Type II
Type I
Transposons
Type IIType I
LTR
Non-LTR
Diversity of transposons
MechanismOf DNA Transposons
Target Site Duplication
MechanismOf DNA Transposons
How does copy number increase ?
How does copy number increase ?
How does copy number increase ?
Can reach high
numbers in the
genome because of
replicative movement.
Retro-Transposons
Type I
Our genome is NOT only ours !
Our genome contains virus !!!!!!
Triggering factors HSV,
EBV
HERV transactivation
Release of virions & Env protein
Super antigen-like activation
Breach of
BBB
? Multiple
Sclerosis
LINES & SINES• LINES-Long Interspersed Nuclear
Elements• About 868,000 in human genome
• 6,500 base pairs long including LTRs
• Encode reverse transcriptase and integrase
• Copy-paste mechanism to insert elsewhere
• SINES-Short Interspersed Nuclear Elements• Millions in human genome
• 100-400 bases long
• Often contain RNA polymerase III promoters but no genes
• ALUs- The most common SINE• 1,500,000 copies = 11% of human genome
• 350 base pairs in length
• Contain an RNA Polymerase III promoter, Alusite
• Appear to evolve from 7S RNA signal recognition particle
Sorghum 700 Mb
Barley 5,000 Mb
Maize 2,500 Mb
Oats ~20,000 MbWheat 20,000 Mb
Rice 450 Mb
Variation in cereal genomes - transposons & genome duplications
• Most TEs are inactive - fossils
How do organisms live with TEs?
How do organisms live with TEs?
•Active TEs evolved to insert into safe sites.
Alu within the Alu
Full Alu sequence
½ Alu sequence
½ Alu sequence
• Host modulation of TE movement• Methylation• Heterochromatin formation• piRNA
How do organisms live with TEs?
SINEs – short
interspersed nuclear
elements (eg Alu)
Transposable element (TE) content of human genome
Alu repeats: ~300 bp long
with AluI restriction site, > 1
million copies in human
genome
SVA composite
retroelement (SINE,
VNTR & Alu)
LINEs – long
interspersed nuclear
elements (eg L1)
Target primed reverse
transcription (TPRT)
• TEs can provide advantages and can be exploited by anorganism like human for his use !
How do organisms live with TEs?
Evolution induction by transposons
Evolution of Placental Mammals
RAG1 and RAG2 in V(D)J recombination and transposition
Obstacle is xenotransplantation
Sleeping Beauty transposon system
Methods for detecting transposons insertions
Transposon tagging