^ Thus, P elements on the paternal chromosomes undergo a burst of transposition—hybrid dysgenesis—.

Sterile fly

^ Thus, P elements on the paternal chromosomes undergo a burst of transposition—hybrid dysgenesis—.

F1 generation

Sterile fly

|4| .resulting in mutations, chromosome aberrations, and sterile offspring.


Conclusion: Only the cross between a P+ male and the P- female causes hybrid dysgenesis, because the sperm does not contribute repressor.

insertion into DNA. All active forms of these transposable elements encode transposase, which is required for their movement. Some also encode resolvase, repressors, and other proteins. Their transposition may be replicative or nonreplicative, but they never use RNA intermediates. Examples of transposable elements in this first class include insertion sequences and all complex transposons in bacteria, the Ac and Ds elements of maize, and the P elements of Drosophila.

The second class of transposable elements are the retrotransposons, which transpose through RNA intermediates. They generate flanking direct repeats at their points of insertion when they transpose into DNA. Retrotransposons do not encode transposase, but some types are similar in structure to retroviruses and carry sequences that produce reverse transcriptase. Transposition

[Table 11.6 Characteristics of two major classes of transposable genetic elements ^

Transposable Genetic Element


Genes Encoded



Class I

Short, terminal inverted repeats; short flanking direct repeats at target site

Transposase gene (and sometimes others)

By DNA intermediate (replicative or nonreplicative)

IS1 (E. coli) Tn3 (E. coli) Ac, Ds (maize) P elements (Drosophila)

Class II


Long, terminal direct repeats; short flanking direct repeats at target site

Reverse transcriptase gene (and sometimes others)

By RNA intermediate

Ty (yeast) copia (Drosophila) Alu (human)

takes place when transcription produces an RNA intermediate, which is then transcribed into DNA by reverse tran-scriptase and inserted into the target site. Examples of retrotransposons in this class include Ty elements in yeast, copia elements in Drosophila, and Alu sequences in humans. Retrotransposons are not found in prokaryotes.

The Evolution of Transposable Elements

As mentioned earlier, transposable elements exist in all organisms, often in large numbers. Why are they so common? Three principal hypotheses have been proposed to explain their widespread occurrence.

The cellular function hypothesis proposes that transpos-able elements serve a valuable function within the cell, such as the control of gene expression or the regulation of development. Although the insertion of a transposable element can alter gene expression, there are few data to suggest that transposition plays a routine role in either of these or any other cellular processes.

The genetic variation hypothesis proposes that transpos-able elements exist because of their mutagenic activity. It suggests that a certain amount of genetic variation is useful because it allows a species to adapt to environmental change. Although some mutations caused by transposable elements may allow species to evolve beneficial traits, the vast majority of mutations generated by random transposition have deleterious effects. Thus, although mutations produced by transposable elements may be useful in the future, their immediate effect is usually deleterious and they will be selected against. The fact that many organisms have evolved mechanisms to regulate transposition suggests that there is selective pressure to limit the extent of transposition. In fact, if their only effect were to generate mutations, transposable genetic elements could be expected to disappear in time.

The selfish DNA hypothesis asserts that transposable elements serve no purpose for the cell; they exist simply because they are capable of replicating and spreading. They can be thought of as "selfish" parasites of DNA that provide no benefit to the cell and may even be somewhat detrimental. Their capacity to reproduce and spread is what makes them common.

Which, if any, of these hypotheses is the correct explanation for the existence of transposable elements is not known. These hypotheses are not mutually exclusive, and all may contribute to the existence of mobile genes. Regardless of the evolutionary forces responsible for their existence, transposable elements have clearly played an important role in shaping the genomes of many organisms. In some cases, they have even been adopted for useful purposes by their host cells. One example is the mechanism that generates antibody diversity in the immune systems of vertebrates.

As will be discussed in Chapter 21, the ability of the immune system to recognize and attack foreign substances (antigens) depends on a mechanism whereby lymphocytes join several DNA segments that code for antigen-recognition proteins. Three DNA segments, called V, D, and J, exist in multiple forms within each cell. In the development of a lymphocyte, particular V, D, and J segments are randomly joined to produce a protein that recognizes a specific antigen. Within different lymphocytes, different V, D, and J segments are joined together in different combinations. The variety of combinations provides a large array of cells, each of which recognizes a particular antigen. Close examination of the V, D, and J joining process reveals that its mechanism is the same as that for transposition. The genes — designated RAG1 and RAG2 — participating in bringing about V, D, and J joining may have at one time been transposable elements that inserted into the germ line of a vertebrate ancestor, some 450 million years ago.

Another cellular function that may have originated as the result of a transposable element is the process that maintains the ends of chromosomes in eukaryotic organisms. As mentioned earlier in this chapter, DNA poly-merases are unable to replicate the ends of chromosomes. In germ cells and single-celled eukaryotic organisms, chromosome length is maintained by telomerase, an enzyme that extends the chromosome ends by copying repeated DNA sequences from an RNA template that is a part of the telomerase enzyme. The mechanism used by the telomerase enzyme is similar to the reverse transcription process used in retrotransposition, and telomerase is evolutionarily related to the reverse transcriptases encoded by certain retrotransposons.

These findings suggest that an invading retrotranspo-son in an ancestral eukaryotic cell may have provided the ability to copy the ends of chromosomes and eventually evolved into the gene that encodes the modern telomerase enzyme. Drosophila lacks the telomerase enzyme; retro-transposons appear to have resumed the role of telomere maintenance in this case.

Connecting Concepts Across Chapters 9

The material covered in this chapter has important connections to several topics already covered and to others in chapters yet to come. In Chapter 2, the gross structure of chromosomes and their behavior during mitosis and meiosis were introduced. The present chapter has built on that introduction by examining the molecular details of chromosome structure and the higher-level folding and packing of DNA that allows these very large molecules to maintain their functionality and still fit into the confined space of the cell. The solution to this cellular storage problem and the essential elements of eukaryotic chromosomes have been major themes of this chapter, completing the story of DNA structure introduced in Chapter 8.

Transposable genetic elements, DNA sequences that move, are a part of chromosome structure. Earlier chapters dealt with crossing over, in which homologous DNA sequences switch places, and chromosome rearrangements, in which the breakage and rejoining of chromosome segments moves blocks of genes to new locations. The movement of transposable elements is fundamentally different from these other mechanisms of gene movement because transposable elements possess sequences that facilitate their movement. Understanding the structure of transposable genetic elements requires a basic knowledge of DNA structure and sequence, topics covered in Chapter 10.

Transposable elements violate a basic premise of classical genetics — that genes have a particular fixed location on a chromosome. This departure from a longheld view helps to explain why the discovery of transpos-able elements by Barbara McClintock was ignored for many years. A common theme in the history of genetics is that fundamental discoveries are often overlooked or unrecognized, because they require a radical rethinking of basic principles. Transposable elements today are recognized as ubiquitous DNA sequences with important implications for medicine, recombinant DNA technology, and evolution, but the reason for their widespread occurrence is still not completely understood.

This chapter has provided a foundation for topics introduced in several later chapters of the book. Transposition requires the replication of DNA (Chapter 12) or reverse transcription (Chapter 14) and generates gene mutations (Chapter 17). In Chapter 16, we explore the control of gene expression, which requires changes in chromatin structure. Condensed chromatin structure tends to inhibit the transcription of genetic information; some of the proteins that take part in activating and repressing transcription are known to affect the binding of DNA to histones. The regulation of transposition is by some of the same mechanisms that regulate the expression of other genes, also discussed in Chapter 16. Additional topics covered in more detail in later chapters include the origins of replication (Chapter 12) and the application of repetitive sequences to DNA fingerprinting (Chapter 18). Transposable elements are important in the generation of immune-system diversity (Chapter 21) and in molecular evolution (Chapter 23).

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