1 & LINEs & SINEs. 2 highly-repetitive interspersed sequences The genome of most eukaryotes...

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LINEs && SINEs

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The genome of most eukaryotes contains highly-repetitive highly-repetitive interspersed sequencesinterspersed sequences:

(1) short-interspersed repetitive elements (SINESINEs)

(2) long-interspersed repetitive elements (LINELINEs).

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~1/2 of the human genome consists of interspersed repetitive sequences.

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interspersed repeats

Original definitions:

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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 The reverse transcriptase has transcriptase has LINELINE specificityspecificity, i.e., a , i.e., a reverse transcriptase reverse transcriptase from one from one LINELINE will only will only recognize the 3’ end of recognize the 3’ end of that that LINELINE, and will be , and will be less efficient at less efficient at recognizing and reverse recognizing and reverse transcribing other transcribing other LINELINEs. s.

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SINESINEs are s are retrosequencesretrosequences that range in length that range in length from 75 to 500 bp. from 75 to 500 bp.

SINESINEs do not possess any s do not possess any reading framereading frame. .

Thus, their Thus, their retroposition retroposition mustmust be be aided by aided by other genetic other genetic elementselements. .

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SINESINE

7SL-RNA derived tRNA-derived

Primate Alu+

Rodent B1 All others

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AluAlu elements elements

• 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)

FAMFAM

FLAMFLAM FRAMFRAM

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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 non-functional & creates new master gene B

Mutation renders B non-functional & creates new master gene C

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AluAlu elements can be elements can be divided into divided into subfamiliessubfamilies

The The subfamilies subfamilies are are distinguished distinguished by ~16 by ~16 diagnostic diagnostic positions.positions.

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diagnosticdiagnosticpositionspositions

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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 Early in primate evolution, evolution, AluAlu transposition rate transposition rate was approximately was approximately one new jump in one new jump in every live birthevery live birth. .

Today, it is about Today, it is about one new jump in one new jump in every 200 live every 200 live birthsbirths. .

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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

twin twin SINESINE500 per haploid genome500 per haploid genome

Culex pipiens

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Norihiro Okada et al.

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Bombyx moriBombyx 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 divergence in Alu sequences and -globin pseudogenes

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Percent divergence

_______________________________________Species pair Alu sequence pseudogene

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Human vs. chimpanzee 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.a. An insertion may obliterate the reading frame (phenotypic effects).

b.b. A transposable element may contain regulatory elements (effects on transcription of nearby genes).

c.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.

39Transposable elements in Antirrhinum majus

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cinnamic acidchalcone eriodictyol dihydroquercetin cyanidin

nivea recurrens

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cinnamic acidchalcone eriodictyol dihydroquercetin cyanidin

nivea incolorata pallida

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rrugosusugosus

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4. Transposable elements promote gross genomic rearrangements

a.a. directly (moving a DNA sequence from one genomic location to another).

b.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 5exon 5 of the low-density-lipoprotein-receptor gene, has given rise to a mutant gene lacking exon 5 (FH-626aFH-626a). Patients homozygous for this deletions have hypercholesterolemiahypercholesterolemia.

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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 8. Replicative transposable elements may be “motif donors” elements may be “motif donors” for for nucleosome positioningnucleosome positioning, , DNA DNA methylationmethylation, , transcription transcription enhancementenhancement, , transcription transcription silencingsilencing, , polyadenylationpolyadenylation, , retinoic-acid receptorsretinoic-acid receptors, , RNA RNA splicingsplicing, , RNA stabilizationRNA stabilization, , RNA transportRNA transport, & , & open-reading open-reading framesframes. .

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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 frequency of mutation.

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Hybriddysgenesis

In PP-carrying flies, there are 30-50 P elements per haploid genome. Many are inactive.

MM flies do not carry P elements.

PP MM

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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

cytotypecytotype

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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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Richard GoldschmidtThe “hopeful monster” idea

“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)

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Genetic resetting

Mass replicative transposition of elements containing elements containing regulatory sequencesregulatory 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 reproductively isolatedisolated 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 incompatibilityIn 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