0
500
1000
1500
2000
2500
3000 Genomic DNA
TE DNA
Protein-codingDNA
Mb
Feschotte & Pritham 2006
TE content correlates positively with genome size
Transposable elements ….
•CONCLUSIONS…•TEs have played an important role in genome evolution and diversification
•Can facilitate expansion and contraction of genomes AND gene families
• Variation in gene numbers cannot explain variation in genome size among eukaryotes
• Most variation in genome size is due to variation in the amount of repetitive DNA (mostly derived from TEs)
• TEs accumulate in intergenic and intronic regions
and continue to play
^
Goals for next two class sessions:
1.Distinguish major transposable element classes: • DNA (transposase)• RNA (reverse transcriptase)
• LTR retrotransposon (integrase)• Non-LTR retrotransposon (TPRT)
• Autonomous• Non-autonomous
2.Presently Active Human TEs• LINE – LINE-1 or L1• SINE – Alu• SVA
3.Consequences of TEs• Genetic (individual)• Evolutionary (species)
Repetitive elements are interspersed throughout mammalian genomes
Han & Boeke, Bioessays 2005 27:775-84.
Summary: DNA transposition
•cis-acting sequences (inverted repeats) recognized by element-encoded transposase enzyme (can be supplied in trans)
•transposase leaves a double-strand break upon excision
•similarities to VDJ recombination (e.g., Rag1) which is believed to be an “exapted” transposon
•staggered break in target DNA at the insertion site causes target site duplications (short, direct repeats) to flank the transposon after transposition is complete and the gaps are repaired
LTR retrotransposons
•Retrotransposition: transposition with an RNA intermediate
•Replication like retroviruses
From Molecular Cell Biol ed 5
First step in LTR retrotransposition: transcription of an integrated copy
From Molecular Cell Biol ed 5
Summary: LTR retrotransposition
•transposition begins with transcription
•LTRs (long terminal repeats) are the critical cis-acting sequences (note: these are direct repeats)
•element encodes reverse transcriptase and integrase enzymes, plus additional proteins required for replication
•RNA copied into double-stranded cDNA in cytoplasm, using a cellular tRNA as the first primer
•integrase catalyzes insertion of the ds-cDNA at a staggered break in target DNA, creating a target site duplication as with transposase
Similarities between DNA transposition and non-LTR retrotransposition
From Molecular Cell Biol ed 5
transposase integrase
Summary: non-LTR retrotransposition
• transposition begins with transcription
• requires element-encoded endonuclease and reverse transcriptase
• cDNA synthesis and insertion of the new copy into chromosomal DNA occurs simultaneously, by TPRT (target-primed reverse transcription)
• newly-inserted elements typically have a polyA tail and target-site duplications
20%
40%
60%
80%
100%
DNA transposons
LTR Retro.
Non-LTR Retro.
Feschotte & Pritham 2006
TE composition varies among eukaryotic genomes
Zhao
F e
t al.
Gen
ome
Res
. 200
9;19
:138
4-13
92
Age distribution of interspersed repeats in the mammoth, human, and opossum genomes
Non-LTR retrotransposons in humans and other eukaryotes
Eickbush & Jamburuthugoda, 2009
Kapi
tono
v et
al.
Gene
, 200
9
Fura
no e
t al.,
Tre
nds
Gen
et. 2
004,
20:
9-14
Dramatically different LINE amplification in human and fish genomes
Boissinot S et al. Genome Res. 2004;14:1221-1231
Structure of a typical full-length human L1 element: note subfamily sequence variation
Mod
ified
from
Boi
ssin
ot, S
. et a
l. M
ol B
iol E
vol 2
001
18:9
26-9
35.
Evolution of L1 in the primate genome
humans only
all great apes, inc Hs
OWM, apes, humans
Bro
uha
B e
t al.
PN
AS
200
3;10
0:52
80-5
285
Chromosomal location, activity, allele frequency, and subclass of 82 full-length L1 elements with two intact ORFs
Modified from Boissinot S et al. PNAS 2006;103:9590-9594
The frequency distribution of polymorphic Ta1 elements
full lengthtruncated
L1Hs insertions found in various human genomes
Ewing A D , Kazazian H H Genome Res. 2010;20:1262-1270
©2010 by Cold Spring Harbor Laboratory Press
Impact of transposable elements on genomes
•A source of genetic novelty
•Alter gene function by insertion
•Induce chromosomal rearrangements
Feschotte, C. Nat Rev Genet. 2008 May; 9(5): 397–405.
TEs can influence gene expression in many ways
Fesc
hotte
, C. N
at R
ev G
enet
. 200
8 M
ay; 9
(5):
397–
405.
Building regulatory systems with transposable elements
Fesc
hotte
, C. N
at R
ev G
enet
. 200
8 M
ay; 9
(5):
397–
405.
DNA-binding proteins and transcription factors derived from transposases
Hedges & Deininger, Mutat Res, 616:46-59
Interspersed repeat-mediated non-allelic homologous recombination
Learning Objectives:
Define and discuss the key similarities and differences among DNA transposons, LTR and non-LTR retrotransposons.
Explain how transposable elements can cause variation among individuals within a species or between species? Explain how transposable elements could act to alter phenotypes between humans, including between “identical” twins.
Distinguish autonomous from non-autonomous transposable elements.
Which TEs are currently active in the human genome?
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