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RECOMBINATION AND TRANSPOSITION AT THE MOLECULAR LEVEL CHAPTER 17 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Transposable Elements And Transposition Transposition transposable elements (TEs) integration of small DNA segments into chromosomes Can occur at many locations within genome “jumping genes” DNA segments that move 1st identified by Barbara McClintock in corn McClintock Discovers Moving Loci in Corn Babara McClintock identified many unusual features of corn chromosomes This observation initiated a six-year study that culminated in 1951 with the following proposal She noticed that in one strain of corn, chromosome 9 tended to break at a high rate at the same site termed this a mutable site or mutable locus Mutable sites are actually locations where transposable elements have been inserted into the chromosomes She received the Nobel Prize in 1983 for this work Transposition Pathways 3 general types of transposition Simple transposition Replicative transposition Retrotransposition Simple Transposition Figure 17.12 Known as Insertion Sequences - IS bacterial Tn10 eukaryotic Ac/Ds Replicative Transposition Figure 17.12 Involves replication of the TE and insertion of the copy into another chromosomal location Only found in bacteria Retrotranposons & Retrotransposition Figure 17.12 Very common but only occurs in eukaryotes These types of elements are termed retroelements or retrotransposons Similar organization to retroviruses Simple & Replicative Transposons Both contain a gene encoding a transposase enzyme Transposase function recognizes direct and indirect repeats cuts DNA for both excision and insertion Regulatory Sequences of Transposable Elements transposon Direct repeats – DNA sequences that are identical and run in the same direction (5’3’) 5’ ATGACTGAC 3’ 3’ TACTGACTG 5’ and 5’ ATGACTGAC 3’ 3’ TACTGACTG 5’ Inverted repeats - DNA sequences that are identical (or very similar) but run in opposite directions 5’ CTGACTCTT 3’ 3’ GACTGAGAA 5’ Figure 17.13 and 5’ AAGAGTCAG 3’ 3’ TTCTCAGTC 5’ Composite Transposons Contain additional genes that are not necessary for transposition per se Only the two inverted repeats at the ends of the transposon are involved in the transposition event Only these are adjacent to direct repeats Figure 17.13 Elements of Replicative Transposons Organization is similar to insertion sequences Resolvase gene is found between the inverted repeats Both enzymes are needed to catalyze the transposition of these types of elements Figure 17.13 Retrotransposons – Retroviral-Like Elements Evolutionarily related to known retroviruses LTR – long terminal repeat uses RNA as a template to synthesize a cDNA (complementary DNA) Int – integrase act as promoters to transcribe viral genes – in this case RT and Int genes RT – reverse transcriptase Retroviruses - RNA viruses that make a DNA copy that integrates into the host’s genome recognizes DR sequences, cuts host DNA and insert retroelement sequences There is no excision of retroelements or retroviruses! There are ~100,000 copies of the L1 retroelement in humans Virtually all have lost function of RT and/or Int genes Non-viral Retroelements Share little sequence similarity with retroviruses derived from normal eukaryotic genes some have RT or RT-like gene, many such genes are not functional Alu family of non-viral retroelements derived from a single ancestral gene known as the 7SL RNA gene has been copied by retroposition to > 500,000 copies ~ 6% of the human genome An example of a SINE – short interspersed element Figure 17.13 Describing Function of Transposable Elements Autonomous contain all the information necessary for transposition to occur Nonautonomous lack a gene or sequence element necessary for transposition If element is missing – transposon will not transpose if Transposase is mutated, element can still transpose if enzyme from another transposon “helps” it McClintock’s Ds element is nonautonomous functional transposase, RT, Int etc… DNA elements – DRs, IRs, LTR, etc… lacks transposase gene McClintock’s Ac locus (Activator) is autonomous has functional transposase enzyme If Ds and Ac are both present in genome, transposition of Ds can occur Transposase Catalyzes Excision & Insertion The enzyme transposase catalyzes the removal of a TE and the its reinsertion at another location Transposase recognize the inverted repeats at the ends of a TE and bring them closer together The remainder of the general scheme for simple transposition is shown in Figure 17.14 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 17-65 Transposase Catalyzes Excision & Insertion Figure 17.14 They are in the same direction and are repeated at both ends of the element Figure 17.14 17-67 Transposable Elements Influence Mutation & Evolution Over the past few decades, researchers have found that transposable elements occur in the genomes of all species Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 17-74 In some cases, repetitive sequences in eukaryotic genomes are due to the proliferation of TEs In mammals, for example LINEs Long interspersed elements Usually 1,000 to 5,000 bp long Found in 20,000 to 100,000 copies per genome SINEs Short interspersed elements Less than 500 bp in length Example: Alu sequence Present in 500,000 to 1,000,000 copies in the human genome Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 17-76 The biological significance of transposons in evolution remains a matter of debate There are two schools of thought 1. TEs exist because they simply can! In other words they are like parasites They can proliferate within the host as long as they do not harm the host to the extent that they significantly disrupt survival This has been termed the selfish DNA theory 2. TEs exist because they offer some advantage Bacterial TEs carry antibiotic-resistance genes TEs may cause greater genetic variability through recombination TEs may cause the insertion of exons into the coding sequences of structural genes This phenomenon, called exon shuffling, may lead to the evolution of genes with more diverse functions Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 17-77 Transposable elements can rapidly enter the genome of an organism and proliferate quickly Drosophila melanogaster A TE known as the P element was introduced into the species in the 1950s Remarkably, in the last 50 years, the P element has expanded throughout D. melanogaster populations worldwide The only strains without the P element are lab stocks collected prior to 1950 Transposable elements have a variety of effects on chromosome structure and gene expression Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 17-78 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 17-79 Transposons Have Become Important Tools in Biology The features of transposons have made them an important experimental tool in molecular biology 1. The introduction of transposons into a cell is a convenient way to abolish the expression of a gene 2. It can be used to clone a particular gene in an approach known as transposon tagging Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 17-81 An early example of transposon tagging involved an X-linked gene in Drosophila that affects eye color Wild-type = red ; Mutant = white In 1981, Paul Bingham, Robert Levis and Gerald Rubin use transposon tagging to clone this gene They started with a wild-type population of Drosophila that carried a transposon called copia From this red-eyed strain, a white-eyed strain was obtained The copia element transposed into the X-linked eye color gene, thereby inactivating it Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 17-82 Figure 17.17 17-83 Figure 17.17 17-84