Transposable elements

SIGNIFICANCE: Transposable elements are discrete DNA sequences that have evolved the means to move (transpose) within the chromosomes. Transposition results in mutation and potentially large-scale genome rearrangements. Transposable elements contribute to the problem of multiple antibiotic resistance by mobilizing the genes of pathogenic bacteria for antibiotic resistance.

Jumping Genes

Transposable elements are DNA sequences that are capable of moving from one chromosomal location to another in the same cell. In some senses, transposable elements have been likened to intracellular viruses. The first genetic evidence for transposable elements was described by Barbara McClintock in the 1940s. She was studying the genetics of the pigmentation of maize (corn) kernels and realized that the patterns of inheritance were not following Mendelian laws. Furthermore, she surmised that insertion and excision of genetic material were responsible for the genetic patterns she observed. McClintock was recognized for this pioneering work with a Nobel Prize in Physiology or Medicine in 1983. It was not until the 1960s that the jumping genes that McClintock postulated were isolated and characterized. The first transposable elements to be well characterized were found in the bacteria Escherichia coli but have subsequently been found in the cells of many bacteria, plants, and animals.

Transposable elements are discrete DNA sequences that encode a transposase, an that catalyzes transposition. Transposition refers to the movement within a genome. The borders of the are defined by specific DNA sequences; often the sequences at either end of the transposable element are inverted repeats of one another. The transposase enzyme cuts the DNA sequences at the ends of the transposable element to initiate transposition and cuts the DNA at the insertion site. The site for insertion of the transposable element is not specific. Therefore, transposition results in random insertion into chromosomes and often results in mutation and genome rearrangement. In many organisms, transposition accounts for a significant fraction of all mutation. Although the details of the mechanism may vary, there are two basic mechanisms of transposition: conservative and replicative. In conservative transposition, the transposable element is excised from its original site and inserted at another. In replicative transposition, a copy of the transposable element is made and is inserted in a new location. The original transposable element remains at its initial site.

A subset of the replicative transposable elements includes the retrotransposons. These elements transpose through an RNA intermediate. Interestingly, their DNA sequence and organization are similar to those of retroviruses. It is likely that either retroviruses evolved from retrotransposons by gaining the genes to produce the proteins for a viral coat or retrotransposons evolved from retroviruses that lost the genes for a viral coat. This is one of the reasons that transposons are likened to viruses. Viruses can be thought of as transposons that gained the genes for a protein coat and thus the ability to leave one cell and infect others; conversely, transposons can be thought of as intracellular viruses.

Genetic Change and Selfish DNA

Transposition is a significant cause of mutation for many organisms. When McClintock studied the genetic patterns of maize kernel pigmentation, she saw the results of insertion and excision of transposable elements into and out of the pigment genes. Subsequently, it has been well established that mutations in many organisms are the result of insertion of transposable elements into and around genes. Transposition sometimes results in deletion mutations as well. Occasionally the transposase will cut at one end of the transposable element but skip the other end, cutting the DNA further downstream. This can result in a deletion of the DNA between the end of the transposable element and the cut site.

In addition to these direct results, it is believed that transposable elements may be responsible for large-scale rearrangements of chromosomes. Genetic recombination, the exchange of genetic information resulting in new combinations of DNA sequences, depends upon DNA sequence homology. Normally, does not occur between nonhomologous chromosomes or between two parts of the same chromosome. However, transposition can create small regions of (the transposable element itself) spread throughout the chromosomes. Recombination occurring between transposable elements can create deletions, inversions, and other large-scale rearrangements of chromosomes.

Scientists often take advantage of transposable elements to construct mutant organisms for study. The random nature of insertion ensures that many different genes can be mutated, the relatively large insertion makes it likely that there will be a complete loss of gene function, and the site of insertion is easy to locate to identify the mutated region.

Biologists often think of natural selection as working at the level of the organism. DNA sequences that confer a selective advantage to the organism are increased in number as a result of the increased reproductive success of the organisms that possess those sequences. It has been said that organisms are simply DNA’s means of producing more DNA. In 1980, however, W. Ford Doolittle, Carmen Sapienza, Leslie Orgel, and Francis Crick elaborated on another kind of selection that occurs among DNA sequences within a cell. In this selection, DNA sequences are competing with each other to be replicated. DNA sequences that spread by forming additional copies of themselves will increase relative to other DNA sequences. There is selection for discrete DNA sequences to evolve the means to propagate themselves. One of the key points is that this selection does not work at the level of the organism’s phenotype. There may be no advantage for the organism to have these DNA sequences. In fact, it may be that there is a slight disadvantage to having many of these DNA sequences. For this reason, DNA sequences that are selected because of their tendency to make additional copies of themselves are referred to as “selfish” DNA. Transposable elements are often cited as examples of selfish DNA.

Composite Transposons and Antibiotic Resistance

Some transposable elements have genes unrelated to the transposition process located between the inverted, repeat DNA sequences that define the ends of the element. These are referred to as composite transposons. Very frequently, bacterial composite transposons contain a gene that encodes resistance to antibiotics. The consequence is that the resistance gene is mobilized: It will jump along with the rest of the transposable element to new DNA sites. Composite transposons may be generated when two of the same type of transposable elements end up near each other and flanking an antibiotic resistance gene. If mutations occurred to change the sequences at the “inside ends” of the transposable elements, the transposase would then only recognize and cut at the two “outside end” sequences to cause everything in between to be part of a new composite transposon.

Resistance to antibiotics is a growing public health problem that threatens to undo much of the progress that the antibiotic revolution made against infectious disease. According to the Centers for Disease Control and Prevention (CDC), five million people died worldwide in 2019 from antibiotic resistant microbes. Transposition of composite transposons is part of the problem. Transposition can occur between any two sites within the same cell, including between the chromosome and DNA. Plasmids are small, circular DNA molecules that replicate independently of the bacterial host chromosome. Resistance plasmids (R plasmids) are created when composite transposons carrying an antibiotic resistance gene insert into a plasmid. What makes this particularly serious is that some plasmids encode fertility factors (genes that promote the transfer of the plasmid from one bacterium to another). This provides a mechanism for rapid and widespread antibiotic resistance whenever antibiotics are used. The great selective pressure exerted by antibiotic use results in the spread of R plasmids throughout the bacterial population. This, in turn, increases the opportunities for insertion into R plasmids to create multiple drug-resistant R plasmids. The first report of multiple antibiotic resistance caused by R plasmids was in Japan in 1957 when strains of Shigella dysenteriae, which causes dysentery, became resistant to four common antibiotics all at once. Some R plasmids encode resistance for up to eight different antibiotics, which often makes treatment of bacterial infection difficult. Furthermore, some plasmids are able to cause genetic transfer between bacterial species, limiting the usefulness of many antibiotics.

Key Terms

• composite transposona transposable element that contains genes other than those required for transposition
• resistance plasmid (R plasmid)a small, circular DNA molecule that replicates independently of the bacterial host chromosome and encodes a gene for antibiotic resistance
• selfish DNAa DNA sequence that has no apparent purpose for the host and that spreads by forming additional copies of itself within the genome
• transposasean enzyme encoded by a transposable element that initiates transposition by cutting specifically at the ends of the element and randomly at the site of insertion

Bibliography

"About Antimicrobial Resistance." Centers for Disease Control and Prevention, 5 Oct. 2022, www.cdc.gov/antimicrobial-resistance/about/index.html. Accessed 6 Sept. 2024.

Boyd, Gregory A. Transposable Elements. New York: Springer, 2012. Print.

Bushman, Frederic. Lateral DNA Transfer: Mechanisms and Consequences. Cold Spring Harbor: Cold Spring Harbor Laboratory, 2002. Print.

Capy, Pierre, et al. Dynamics and Evolution of Transposable Elements. New York: Chapman, 1998. Print.

Galun, Esra. Transposable Elements: A Guide to the Perplexed and the Novice, with Appendices on RNAi, Chromatin Remodeling, and Gene Tagging. Boston: Kluwer Academic, 2003. Print.

Kazazian, Haig H. Jr. Mobile DNA: Finding Treasure in Junk. Upper Saddle River: FT, 2011. Print.

Keller, Evelyn Fox. A Feeling for the Organism: The Life and Work of Barbara McClintock. 10th anniversary ed. New York: Freeman, 1993. Print.

McClintock, Barbara. The Discovery and Characterization of Transposable Elements: The Collected Papers of Barbara McClintock. New York: Garland, 1987. Print.

McDonald, John F., ed. Transposable Elements and Genome Evolution. London: Kluwer Academic, 2000. Print.

Peterson, Thomas. Plant Transposable Elements: Methods and Protocols. New York: Humana, 2013. Print.

Wells, Jonathan N., and Cédric Feschotte. "A Field Guide to Eukaryotic Transposable Elements." Annual Review of Genetics, vol. 54, 21 Sept. 2020, pp. 539–561, doi: 10.1146/annurev-genet-040620-022145. Accessed 6 Sept. 2024.