LINEs

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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 Non-LTR
retrotransposons and degenerate descendants of
retrotransposons. SINEs Non-autonomous
non-LTR retrotransposons (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
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Alu elements

• Length 300 bp
• Repetitive gt 1,000,000 times in the human genome
• Constitute gt10 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
Progeny undergoes multiple independent mutations
Replicatively incompetent progeny
Master gene A
Mutation renders A non-functional creates new
master gene B
Mutation renders B non-functional 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. ? 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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Culex pipiens
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Bombyx mori
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Norihiro Okada et al.
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3 predictions 1. Where theres a SINE, theres
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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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
incolorata
pallida
cinnamic acid
chalcone
eriodictyol
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-lipopro
tein-receptor 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.
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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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Margaret Kidwell
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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.
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(1) failure of the gonads to develop if exposed
to temperatures above 27C, (2) recombination in
males, (3) chromosomal breakages, (4) distortion
of Mendelian transmission ratios, and (5) a high
frequency of mutation.
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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.