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.

Maize / Corn

Why are these kernels spotted ?

10

11

12

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 !!!!!!

HERV - K

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

LINE

LINE

LINE

LINE

SINE needs LINE

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)

Alufamily

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