Structure of IS elements.

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These and other transposons have inverted terminal repeats (numerals) and are flanked by direct repeats of host DNA target sequences (letters).

A model for the generation of direct repeats of the target sequence by

transposon insertion.

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Properties of Some Insertion Elements.

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A map of transposon Tn3.

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Total size 4957 bp. Inverted terminal repeats 38 bp each

A composite transposon.

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The IS-like modules may have either (a) direct or (b) inverted relative orientations.

Electron micrograph of a single-stranded circular DNA containing

a transposon.

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The cut-and-paste transposition mechanism catalyzed by Tn5

transposase.

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Cut and paste transposition

How the cut is performed

Comparison of transposition pathways.

Grey segments represent transposable DNA elements. Small arrows indicate phosphodiester bond breakage. Solid and dotted lines represent donor and target DNA, respectively

X-Ray structure of Tn5 transposase.

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in complex with a 20-bp DNA containing the OE sequence

Replicative transposition.

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This type of transposition inserts a copy of the transposon at the target site while another copy remains at the donor site.

A cointegrate.

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This structure forms by the fusion of two plasmids, one carrying a transposon, such that both junctions of the original plasmid are spanned by transposons with the same orientation (arrows).

A model for transposition involving the intermediacy of a cointegrate.

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Here more lightly shaded bars represent newly synthesized DNA.

Chromosomal rearrangement via recombination.

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(a) The inversion of a DNA segment between two identical transposons with inverted orientations.

Chromosomal rearrangement via recombination..

(b) The deletion of a DNA segment between two identical transposons with the same orientation

The mechanism of phase variation in Salmonella.

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hin codes for Hin DNA invertase

hix : Two sites, closely related, 26 bp (2 x 12 bp imperfect inverted repeats separated by 2 bp)

H1, H2: Genes for two antigenically distinct flagellin proteins

rh1: Gene for H1 gene repressor

Størrelse av genomer

Sammensetning av genomet

Repetitive DNA

Iinterspersedinterspersed in tandemin tandem

Moderately Repetitive Sequences in the Human Genomea

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Klasser av intersperserte repetisjoner i det humane genom

Elementer i det humane genom som kan transposeres på en RNA-formidlet måte

Alu elementsLength = ~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).

Evolution of Alu elements

Alu elements can be divided into subfamilies

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

Transposisjonering av et typisk humant Alu-element

Alu-elementer hos primater

Alu sequences in the globin gene cluster

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Gene sequences of (a) retroviruses and(b) the Ty1 retrotransposon from yeast.

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Naturally occuring methylated bases in DNA

The catalytic mechanism of 5-methylcytosine methyltransferases

(m5C-MTases).

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X-Ray structure of M.HhaIP

age

1206

in complex with S-adenosylhomocysteine and a duplex 13-mer DNA containing a methylated f5C residue at the enzyme’s target site.

Maintenance methylation.

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CpG-frekvens og CpG-øyer

The typical density of CpG doublets in mammalian DNA is ~1/100 bp, as seen for a -globin gene. In a CpG-rich island, the density is increased to >10 doublets/100 bp. The island in the APRT gene starts ~100 bp upstream of the promoter and extends ~400 bp into the gene. Each vertical line represents a CpG doublet.

CpG-øyer

Vedlikeholdsmetylering

Ved maintenance-metylering induserer metyleringsmønsteret i en parental DNA-tråd det tilsvarende metyleringsmønster i den komplementære tråden. Slik kan et stabilt metyleringsmønster opprettholdes i en cellelinje

CpG – underrepresentert i genomet

The CpG doublet occurs in vertebrate DNA at only ~20% of the frequency that would be expected from the proportion of G·C base pairs. (this is because CpG doublets are methylated on C, and spontaneous deamination of methyl-C converts it to T, introducing a mutation that removes the doublet.) In certain regions, however, the density of CpG doublets reaches the predicted value; in fact, it is increased by 10× relative to the rest of the genome. The CpG doublets in these regions are unmethylated

Cytosin, metylcytosin og tymin

Tme

Evolusjon av CpG-øyer: en mulig mekanisme

Ancestralt eukaryot genom med metylering av C i CpG, bortsett fra i visse genassosierte områder

Metylerte CpG muteres gradvis til TpG eller CpA, mens umetylerte CpG forblir

Microsatellite terminology

Trinucleotide expansion diseasesTABLE 1

DISEASES OF TRINUCLEOTIDE REPEATS

NAME OF THE DISEASE SEQUENCE OF THE REPEAT

LOCATION OF THE REPEAT

Fragile site 11B Fragile X syndrome

CGG EXON

Dentatorubral-pallidoluysian atrophy Haw river syndrome Huntington's disease Machado-Joseph disease Spinal and Bulbar muscular dystrophy Spinocerebellar ataxia type 1

CAG EXON

Myotonic dystrophy CTG EXON

Friedrich's ataxia GAA INTRON

The loop-out mechanism for the alteration of the number of consecutive triplet

repeats in DNA through its replication.

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