Transcript No Slide Title

LINEs & SINEs
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The genome of most eukaryotes
contains highly-repetitive
interspersed sequences:
(1) short-interspersed repetitive
elements (SINEs)
(2) long-interspersed repetitive
elements (LINEs).
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~1/2 of the human genome
consists of interspersed repetitive
sequences.
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Original definitions:
interspersed repeats
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Current definitions:
LINEs = Active or degenerate
descendants of transposable elements.
SINEs = Non-autonomous
transposable elements (lacking the
ability to mediate their own
transposition) and their degenerate
descendents.
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The reverse transcriptase has
LINE specificity, i.e., a reverse
transcriptase from one LINE will
only recognize the 3’ end of that
LINE, and will be less efficient at
recognizing and reverse
transcribing other LINEs.
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SINEs are retrosequences that
range in length from 75 to 500 bp.
SINEs do not possess any reading
frame.
Thus, their retroposition must be
aided by other genetic elements.
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SINE
7SL-RNA derived
tRNA-derived
Primate Alu
+
Rodent B1
All others
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Alu elements
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Length = ~300 bp
Repetitive: > 1,000,000 times in the human genome
Constitute >10% of the human genome
Found mostly in intergenic regions and introns
Propagate in the genome through retroposition (RNA
intermediates).
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Evolution of Alu elements (I)
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Evolution of Alu elements (II)
FAM
FLAM
FRAM
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Master-gene model for Alu
proliferation in the genome
Master gene A
Replicatively
incompetent
progeny
Progeny undergoes
multiple independent
mutations
Mutation renders A nonfunctional & creates new
master gene B
Mutation renders B nonfunctional & creates new
master gene C
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Alu elements can be divided
into subfamilies
The subfamilies are
distinguished by
~16 diagnostic
positions.
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diagnostic
positions
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Alu elements are found only in
primates.

All the millions of Alu elements
have accumulated in a mere
~65 million years.
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Alu elements can be sorted into
distinct families according to
shared patterns of variation.
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At any given point in time, only
one or several Alu “master
copies” are capable of
transposing.
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Early in primate evolution,
Alu transposition rate was
approximately one new
jump in every live birth.
Today, it is about one new
jump in every 200 live
births.
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PV92, a human-specific Alu insertion on
chromosome 16
There are two alleles: with (+) or without (–) the
Alu transposable element. There are three
genotypes (++, + –, ––). The + and – alleles can be
separated by size using gel electrophoresis.
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tRNA derived SINEs
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a tRNA-derived SINE
Culex pipiens
twin SINE
500 per haploid genome
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Norihiro Okada et al.
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Bombyx mori
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3 predictions:
1. Where there’s a SINE, there’s a
LINE!
2. Once a LINE partner becomes
inactive, the SINE partner will lose its
ability to retrotranspose.
3. A LINE partner should have a
longer evolutionary history and, hence,
a broader phylogenetic distribution
than its SINE partner.
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Degrees of sequence di vergence in Alu sequences and -globin pseudogenes
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Percen t divergence
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Species pair
Alu sequence
 pseudogene
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Human vs. chim panzee
2.2 ± 1.4
1.7
Human vs. orangutan
3.7 ± 1.9
3.1
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GENETIC AND EVOLUTIONARY
EFFECTS OF TRANSPOSITION
1. Duplicative transposition increases
genome size.
Lily
Edible frog
Sunflower
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2. Bacterial transposons often carry
genes that confer antibiotic or other
forms of resistance. Plasmids can
carry such transposons from cell to
cell, so that resistance can spread
throughout a population or an
ecosystem.
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A figure used by Barbara
McClintock at her Nobel
Prize (1983) Lecture
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3. Gene expression may be altered by
the presence of a transposable element.
a. An insertion may obliterate the
reading frame (phenotypic effects).
b. A transposable element may
contain regulatory elements (effects on
transcription of nearby genes).
c. Transposable elements may contain
splice sites (effects on RNA processing
even if the element is in an intron).
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Caused by the insertion of a
transposable element.
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Transposable elements in Antirrhinum majus
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nivea recurrens
cinnamic acid
chalcone
eriodictyol
dihydroquercetin
cyanidin
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nivea
cinnamic acid
incolorata
chalcone
eriodictyol
pallida
dihydroquercetin
cyanidin
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rugosus
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4. Transposable elements promote gross genomic
rearrangements
a. directly (moving a DNA sequence
from one genomic location to another).
b. indirectly (as a result of
transposition, two sequences become
similar to one another so that unequal
crossing-over between them is possible).
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An unequal crossing-over event facilitated by the
presence of multiple Alu sequences in the introns
flanking exon 5 of the low-density-lipoproteinreceptor gene, has given rise to a mutant gene
lacking exon 5 (FH-626a). Patients homozygous
for this deletions have hypercholesterolemia.
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5. Insertion of transposable elements into
some members of a multigene family but not
others will reduce the rate and limit the
extent of gene conversion between the
members of the family and, therefore,
increase the rate of divergence between
duplicate genes.
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6. Some transposable elements cause an
increase in the rate of mutation in
adjacent regions.
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7. The presence of a transposable element
can turn an otherwise immobile piece of
DNA into a mobile one.
IS
IS
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8. Replicative transposable elements may be
“motif donors” for nucleosome positioning,
DNA methylation, transcription
enhancement, transcription silencing,
polyadenylation, retinoic-acid receptors,
RNA splicing, RNA stabilization, RNA
transport, & open-reading frames.
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Hybrid dysgenesis in
Drosophila is a syndrome
of correlated abnormal
genetic traits that is
spontaneously induced in
one type of hybrid between
certain mutually interactive
strains, but not in the
reciprocal hybrid.
Margaret Kidwell
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(1) failure of the gonads to develop if exposed to
temperatures above 27˚C, (2) recombination in males,
(3) chromosomal breakages, (4) distortion of
Mendelian transmission ratios, and (5) a high
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frequency of mutation.
P
M
Hybrid
dysgenesis
In P-carrying flies,
there are 30-50 P
elements per haploid
genome. Many are
inactive.
M flies do not carry P
elements.
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A 2,907-bp P element in D. melanogaster. The element contains a single gene
encoding a transposase (766 amino acids). The coding region consists of four
exons interrupted by three introns. Production of the functional protein
depends on the splicing of the third intron. The splicing of this intron is
prevented by the binding of a multiprotein complex to exon 2. One component
of this complex has a low abundance in germline cells, effectively limiting the
production of functional transposase to these cells only. In somatic cells, a
shorter and inactive polypeptide is encoded by the mRNA that retains the
third intron.
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Hybrid dysgenesis
cytotype
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Speciation (cladogenesis) =
the creation of two or more
taxa from a parental taxon.
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Why NOT hybrid dysgenesis?
Because of segregation distortion, P
quickly spreads through the population.
P has the ability to move from individual
to individual as an infectious agent.
Hybrid dysgenesis was only found in
Drosophila mealnogaster and may not be a
universal phenomenon.
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“The change from species to
species is not a change involving
more and more additional
atomistic changes, but a complete
change of the primary pattern or
reaction system into a new one,
which afterwards may again
produce intraspecific variation by
micromutation.” (Richard
Goldschmidt. 1940. The Material
Basis of Evolution, pp. 205-206)
Richard Goldschmidt
The “hopeful monster” idea
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Genetic resetting
Mass replicative transposition of
elements containing regulatory
sequences in one population may
cause many genes to be subject to
novel modes of regulation.
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A genetically reset population
will become reproductively
isolated from the population
that retains the old form of
gene regulation.
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The discovery that some Alu
repeats contain retinoic-acid
response elements, which may
function as transcription factors,
indicates that it is possible to alter
the expression of numerous genes
through the dispersion of
transposable elements.
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Mechanical incompatibility
In one population the transposable elements
multiply to such an extent as to cause a
significant increase in the size of the
chromosomes.
A hybrid organism that inherits big
chromosomes from one parent and small
chromosomes from the other would experience
difficulties in chromosome pairing during
meiosis, and would be most probably be sterile.
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Thursday, April 26, 2012
Tuesday, May 8, 2012 final exam
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