第五章 转座子和逆转座子

Transposons and retrotansposons

The Sun1642 tomato variety produces an elongated fruit, which is

produced by a duplication that arose as a result of the presence of
the transposable element Rider.
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 Transposable
Elements
( transposons)
A DNA sequence
capable of moving
( transposing) from
one location to
another in a
genome.

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Discovery of Transposable Elements

 McClintock’s experiments in maize:

the Ds element
1940-1950

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 Indian corn, 10 chromosomes
numbered from largest (1) to smallest (10)

Ds (for Dissociation ) located at the site of the break

Ac (for Activator ) unlinked genetic factor, present in
some maize stocks but absent in others 4
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 Transposable element in E. coli , 1960

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Categorization of transposable elements by transposition mechanism

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 第一节 细菌的转座因子
Transposable Elements in Bacteria

Two major groups:

 Simple transposable elements which
carry only the information required for
movement
 Complex transposable elements which
contain DNA sequences not directly
related to transposition

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1. Insertion sequences ( IS)
( 插入序列)

Insertion sequences ( IS) are the

simplest transposons

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The structure of IS element

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 An IS element ends in short inverted
terminal repeats ; usually the two copies of
the repeat are closely related rather than
identical.
 IS elements code for the transposase
 When an IS element transposes, a
sequence of host DNA at the site of
insertion is duplicated.

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Duplication of a short sequence
of DNA at the insertion site

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The IS elements are
normal constituents of
bacterial chromosomes
and plasmids.

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Formation of a conjugative R plasmid by
recombination between IS elements

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2. Composite Transposons

Composite transposons contain a

variety of genes that reside between two
nearly identical IS elements
Composite transposon is designated by
Tn, followed by a number

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 In some cases, IS modules are identical,
such as Tn9 (direct repeats of IS1) or
Tn903 (inverted repeats of IS903).
 In other cases, the modules are closely
related, but not identical. So we can
distinguish the L and R modules in Tn10
or in Tn5.

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A schematic map of a plasmid carrying simple and
composite transposon-resistance genes.
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 A functional IS module can transpose
either itself or the entire transposon.
 When the two IS modules are identical,
either module can sponsor the
transposition.
 When the modules are different,
transposition can depend on one of the
modules

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3. Noncomposite transposons

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Replicative transposition of Tn3

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 由转座因子建立突变库

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 第二节 真核生物的转座因子
Transposable Elements in Eukaryotes

 DNA transposons (cut and paste transposons)

 Ac and Ds elem ents in maize
 P elem ents in Drosophila
 Retrotransposons

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1. The Ac-Ds system in maize
（玉米的Ac-Ds 转座系统）
Barbara McClintock (1902-1992)
1940s ~ 1950s
1983 Nobel Prize

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See movie

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Effects of transposable elements in corn

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Transposable element in other plants

peas snapdragons 30
2. P element transposons in Drosophilia
果蝇的P因子

Hybrid dysgenesis: a condition causing sterility,

elevated mutation rate, and a chromosome
rearrangement in the offspring of crosses between
certain strains of fruit flies.

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Somatic cells contain a
protein that binds to
sequences in exon 3 to
prevent splicing of the
last intron

The absence of this protein

in germline cells allows
splicing to generate the
mRNA that codes for the
transposase
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The 66KD
repressor
protein is
provided as a
maternal
factor in the
egg.

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P-element-
mediated gene
transfer in
Drosophila

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 3. 逆转录病毒与逆转座子
Retroviruses and Retroposons

Retroviruses are single-stranded

RNA animal viruses that employ a
double-stranded DNA intermediate for
replication.

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※The life cycle of a retrovirus※ 38
The typical genome of
a retrovirus contains
gag, pol, and env 逆转录病毒
genes 基因表达
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 The viral DNA integrates into the host
genome at randomly selected sites.
 Sometimes (probably rather rarely), the
integrated retrovirus can convert a host
cell into a tumorigenic state through
activating certain types of host genes.

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Retroposon

Transposable elements that utilize

reverse transcriptase to transpose
through an RNA intermediate are
termed retrotransposons.

（逆转录转座子是指通过RNA为中介,反转录成
DNA后进行转座的转座因子。逆转座作用出现
在真核生物 ）
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 Retroposons in eukaryotes are generally
divided into two classes

◇ Viral retrotransposons(病毒样逆转座子):
resembles retroviruses, but differ from them in not
forming viral particle
Yeast Ty elements, Drosophila copia elements
◇ Nonviral retrotransposons (非病毒样逆转
座子) : do not code for reverse transcriptase and/or
integrase, transposition depends on enzymes coded
elsewhere.
LINEs (long interspersed elements) and SINEs in
mammals

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Structural comparison of a retrovirus to
retrotransposons found in eukaryotic genomes

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  Yeast Ty elements

 About 35 Ty1 copies in the yeast genome.

 δ sequences : 330 bp, about 100 copies.
 solo δ element
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 *

Transposition Base substitution for

marking one δ

through an RNA
intermediate

* 47
 Drosophila copia elements

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第三节 转座的遗传学效应
Genetic Effects of Transposition

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 The Frequency of Transposition

 The frequency varies among different elements.

 The overall rate of transposition is 10-3 ~ 10-4
per element per generation.
 New germ-line transpositions are estimated to occur
once in every 50 to 100 human births
 Insertions in individual targets occur at a level
comparable with the spontaneous mutation
rate, usually 10-5 ~ 10-7 per generation.

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 Transposable elements as
genomic parasites

 Replication and spread of TEs may serve no

purpose for the cell
 The insertion of TEs into a gene will often
destroy its function, with harmful
consequences for the cell
 The time and energy required to replicate
large numbers of TEs are likely to place a
metabolic burden on the cell

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Transposable elements shape the
genomes of many organisms
Transposable Elements in Human
Element type Length Copies in genome % of genome
LINEs 1-6kb 850,000 21
SINEs 100-500bp 1,500,000 13
LTR elements <5kb 443,000 8
DNA elements 80-300bp 294,000 3
Unclassified - 3,000 0.1

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The Alu sequences make up more than 10% of the human genome.

Repetitive elements found in the human gene (HGO )

coding for homogentisate 1,2-dioxygenase, the enzyme
whose deficiency causes alkaptonuria （黑尿病）
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 Transposable elements in grasses are
responsible for genome size differences

cluster of transposons
genes
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Transposable elements and
genetic variation

 Gene mutations

 Rearrangements of the genome

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Transposable elements-induced Mutations in Drosophila

About 50% of all spontaneous mutations in Drosophila

are due to transposition, 10%(mouse), 0.2%(human)
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Retrotransposon-induced
mutations in grape skin color

SCIENCE, 14 MAY 2004, VOL 304

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 Most human transposons appear to be inactive

 As of 2009, at least 11 cases of human diseases are

determined due to insertions of LINE elements
 dystrophin gene, APC and c-myc genes
 SINE insertions are also responsible for more than 30
cases of human disease
 BRCA2 gene, factor IX gene, ChE, NF1 gene, etc􀁓􀁓
 A transposon "caught in the act”
 A male child with hemophilia, blood-clotting factor VIII on X
chromosome

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Transposable elements can cause
rearrangements of the genome

deletion inversion
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 Transposable elements can relocate genes

Imprecisely excise of transposable elements:

• MULEs and Pack-MULEs
• More than 3000 Pack-MULEs in rice genome

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The evolution of new genes through
transposons---- Domestication of
Transposable Elements

 A. thaliana transcription factors

 Drosophila telomeres
 Human recombinase enzymes

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 Host regulation of transposable
elements
 How do plants and animals survive and thrive
with so many insertions in genes and so much
mobile DNA in the genome?
 Insertions into exons are negative selection. Successful
transposable elements insert into so-called safe havens
in the genome (retrotransposons, centric
heterochromatin, introns)
 Most TEs in the genome are inactive, being the relics
that have accumulated inactivating mutations over
evolutionary time
 Others are still capable of movement but are rendered
inactive by host regulatory mechanisms.
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 Epigenetic regulation
 Reversible changes in Ac activity
 Transgene silencing

 A genomic battleground
 A constant battle between the proliferation of
transposable elements and host attempts to
silence or otherwise inactivate them.
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 思考题：
 Explain the reasons of the accumulation of
drug-resistance genes and the appearance of
multiple resistant bacteria

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 The figures and tables are cited from:

 Genetics (From genes to genomes), Leland

Hartwell, Mcgraw-Hill Companies, Inc
 Concept of Genetics, William S.Klug, Prentice Hall,
Inc
 Introduction to Genetics Analysis, Anthony J.F.
Griffiths, W.H.Freeman, Inc
 Principle of Genetics, D.Peter Snustad, John Wiley
& Sons, Inc
 Genetics-A Conceptual Approach, Benjamin A.
Pierce, W. H. Freeman

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