Download TE content correlates positively with genome size

TE content correlates positively with genome size
Mb
Genomic DNA
3000
2500
TE DNA
2000
Protein-coding
DNA
1500
1000
500
0
Feschotte & Pritham 2006
Transposable elements ….
• 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
•CONCLUSIONS… and continue to play
•TEs have played^an important role in genome evolution
and diversification
•Can facilitate expansion and contraction of genomes AND
gene families
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.
DNA transposons
transposase
From Molecular Cell Biol ed 5
Overview of DNA transposition
From Molecular Cell Biol ed 5
Summary: DNA transposition
•cis-acting sequences (inverted repeats) recognized by elementencoded 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
Second step in LTR retrotransposition: cDNA synthesis
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
transposase
From Molecular Cell Biol ed 5
integrase
Retrotransposition: the non-LTR retrotransposon, L1
Han & Boeke, Bioessays 2005 27:775-84.
Non-LTR retrotransposons insert by TPRT
Belancio V P et al. Genome Res. 2008;18:343-358
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
TE composition varies among eukaryotic genomes
100%
80%
60%
DNA transposons
LTR Retro.
40%
Non-LTR Retro.
20%
Feschotte & Pritham 2006
Major groups of DNA transposons are widespread in eukaryotes
TE composition varies among vertebrate genomes
Zhao F et al. Genome Res. 2009;19:1384-1392
Age distribution of interspersed repeats in the mammoth, human, and
opossum genomes
~45% of the human genome is derived from transposable elements
Cordaux & Batzer, 2009, v10, 691-703
Eickbush & Jamburuthugoda, 2009
Kapitonov et al. Gene, 2009
Non-LTR retrotransposons in humans and other eukaryotes
Furano et al., Trends Genet. 2004, 20:9-14
Dramatically different LINE amplification in human and fish genomes
Structure of a typical full-length human L1 element:
note subfamily sequence variation
Boissinot S et al. Genome Res. 2004;14:1221-1231
humans only
all great apes,
inc Hs
OWM, apes,
humans
Modified from Boissinot, S. et al. Mol Biol Evol 2001 18:926-935.
Evolution of L1 in the primate genome
Brouha B et al. PNAS 2003;100:5280-5285
Chromosomal location, activity, allele frequency, and subclass of 82
full-length L1 elements with two intact ORFs
L1 activity distribution
Brouha B et al. PNAS 2003;100:5280-5285
The frequency distribution of polymorphic Ta1 elements
full length
truncated
Modified from Boissinot S et al. PNAS 2006;103:9590-9594
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
TEs can influence gene expression in many ways
Feschotte, C. Nat Rev Genet. 2008 May; 9(5): 397–405.
Feschotte, C. Nat Rev Genet. 2008 May; 9(5): 397–405.
Building regulatory systems with transposable elements
Feschotte, C. Nat Rev Genet. 2008 May; 9(5): 397–405.
DNA-binding proteins and transcription factors derived from transposases
Mechanisms by which L1 retrotransposition can disrupt genes
Han & Boeke, Bioessays 2005 27:775-84.
L1 can create novel functional alleles in several ways
Han & Boeke, Bioessays 2005 27:775-84.
How Retrotransposons Affect the Cell
Goodier & Kazazian, Cell, 2008,135:23-35
How the Cell Affects Retrotransposons
Goodier & Kazazian, Cell, 2008,135:23-35
Interspersed repeat-mediated non-allelic homologous recombination
Hedges & Deininger, Mutat Res, 616:46-59
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?