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Transposable Genetic Elements

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Transposable elements:

  • General features of transposable elements

  • Prokaryotic transposable elements

  • Eukaryotic transposable elements

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Transposable element: mobile genetic elements of a chromosome that have the capacity to move from one location to another in the genome.

  • Normal and universal components of prokaryote and eukaryote genomes.

Prokaryotes-transpose to/from cell’s chromosome, plasmid, or a phage chromosome.

Eukaryotes-transpose to/from same or a different chromosome.

  • Nonhomologous recombination: transposable elements insert into DNA that has no sequence homology with the transposon.

  • Transposable elements cause genetics changes and make important contributions to the evolution of genomes:

    • Insert into genes.

    • Insert into regulatory sequences; modify gene expression.

    • Produce chromosomal mutations.

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Transposable elements:

Two classes of transposable elements/mechanisms of movement:

  1. Encode proteins that (1) move DNA directly to a new position or (2) replicate DNA and integrate replicated DNA elsewhere in the genome (prokaryotes and eukaryotes).

  • Retrotransposons encode reverse transcriptase and make DNA copies of RNA transcripts; new DNA copies integrate at different sites (eukaryotes only).

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Transposable elements in prokaryotes:

Two examples:

  1. Insertion sequence (IS) elements

  • Transposons (Tn)

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Insertion sequence (IS) elements:

  1. Simplest type of transposable element found in bacterial chromosomes and plasmids.

  • Encode gene (transposase) for mobilization and insertion.

  • Range in size from 768 bp to 5 kb.

  • IS1 first identified in E. coli’s glactose operon is 768 bp long and is present with 4-19 copies in the E. coli chromosome.

  • Ends of all known IS elements show inverted terminal repeats (ITRs).

Fig. 7.19

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Insertion sequence (IS) elements:

Integration of an IS element may:

  • Disrupt coding sequences or regulatory regions.

  • Alter expression of nearby genes.

  • Cause deletions and inversions in adjacent DNA.

  • Result in crossing-over.

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Transposition of insertion sequence (IS) elements:

  1. Original copy remains in place; new copy inserts randomly.

  • Transposition requires transposase, coded by the IS element.

  • IS element otherwise uses host enzymes for replication.

  • Transposition initiates when transposase recognizes ITRs.

  • Site of integration = target site.

  • Staggered cuts are made in DNA at target site by transposase, IS element inserts, DNA polymerase and ligase fill the gaps (note---transposase behaves like a restriction enzyme).

  • Small direct repeats (~5 bp) flanking the target site are created.

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Fig. 7.20, Integration of IS element in chromosomal DNA.

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Transposons (Tn):

  • Similar to IS elements but are more complex structurally and carry additional genes

  • 2 types of transposons:

    • Composite transposons

    • Noncomposite transposons

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Composite transposons (Tn):

  • Carry genes (example might be a gene for antibiotic resistance) flanked on both sides by IS elements.

  • Tn10 is 9.3 kb and includes 6.5 kb of central DNA (includes a gene for tetracycline resistance) and 1.4 kb inverted IS elements.

  • IS elements supply transposase and ITR recognition signals.

Fig. 7.21a

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Noncomposite transposons (Tn):

  • Carry genes (example might be a gene for antibiotic resistance) but do not terminate with IS elements.

  • Ends are non-IS element repeated sequences.

  • Tn3 is 5 kb with 38-bp ITRs and includes 3 genes; bla (β-lactamase), tnpA (transposase), and tnpB (resolvase, which functions in recombination).

Fig. 7.21b

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Transposable elements in eukaryotes:

Barbara McClintock (1902-1992)

Cold Spring Harbor Laboratory, NY

Nobel Prize in Physiology and Medicine 1983

“for her discovery of mobile genetic elements”

  • Studied transposable elements in corn (Zea mays) 1940s-1950s

(formerly identified as mutator genes by Marcus Rhoades 1930s)

  • Also known for work demonstrating crossing over as part of the chromosomal basis of inheritance.

  • Biographical sketch, pp. 155-156

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General properties of plant transposons:

  • Possess ITR sequences and generate short repeats at target sites.

  • May activate or repress target genes, cause chromosome mutations, and disrupt genes.

  • Two types:

    • Autonomous elements transpose themselves; possess transposition gene.

    • Nonautonomous elements do not transpose themselves; lack transposition gene and rely on presence of another Tn

  • McClintock demonstrated purple spots in otherwise white corn (Zea mays) kernels are results of transposable elements.

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McClintock’s discovery of transposons in corn:

  • c/c = white kernels and C/- = purple kernels

  • Kernal color alleles/traits are “unstable”.

  • If reversion of c to C occurs in a cell, cell will produce purple pigment and a spot.

  • Earlier in development reversion occurs, the larger the spot.

  • McClintock concluded “c” allele results from a non-autonomous transposon called “Ds” inserted into the “C” gene (Ds = dissassociation).

  • Autonomous transposon “Ac” controls “Ds” transposon (Ac = activator).

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Transposon effects on corn kernel color.

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McClintock’s discovery of transposons in corn (cont.):

  • Ac element is autonomous/Ds element is nonautonomous.

  • Ac is 4,563 bp with 11 bp ITRs and 1 transcription unit encoding an 807 amino acid transposase.

  • Ac activates Ds; Ds varies in length and sequence, but possesses same ITRs as Ac.

  • Many Ds elements are deleted or rearranged version of Ac; Ds element derived from Ac.

  • Ac/Ds are developmentally regulated; Ac/Ds transpose only during chromosome replication and do not leave copies behind.

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Ac transposition mechanism during chromosome replication.

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Ty elements in yeast:

  • Similar to bacterial transposons; terminal repeated sequences, integrate at non-homologous sites, with target site duplication.

  • Ty elements share properties with retroviruses, retrotransposons:

    • Synthesize RNA copy and make DNA using reverse transcriptase.

    • cDNA integrates at a new chromosomal site.

Fig. 7.26

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Human retrotransposons:

Alu1 SINEs (short-interspersed sequences)

  • ~300 bp long, repeated 300,000-500,000X.

  • Flanked by 7-20 bp direct repeats.

  • Some are transcribed, thought to move by RNA intermediate.

  • AluI SINEs detected in neurofibromatosis (OMIM1622200) intron; results in loss of an exon and non-functional protein.

L-1 LINEs (long-interspersed sequences)

  • 6.5 kb element, repeated 50,000-100,000X (~5% of genome).

  • Contain ORFs with homology to reverse transcriptases; lacks LTRs.

  • Some cases of hemophilia (OMIM-306700) known to result from newly transposed L1 insertions.

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Applications:-�

1:Plant molecular biology

2:Identifying cancerous genes

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Thanks