In the 1940s, Barbara McClintock made an astonishing discovery while studying the colored kernels of so-called Indian corn, known as maize (see the Model Organism box). Maize has 10 chromosomes, numbered from largest (1) to smallest (10). While analyzing the breakage of maize chromosomes, McClintock noticed some unusual phenomena. She found that, in one strain of maize, chromosome 9 broke very frequently and at one particular site, or locus (Figure 15-2). Breakage of the chromosome at this locus, she determined, was due to the presence of two genetic factors. One factor that she called Ds (for Dissociation) was located at the site of the break. Another, unlinked genetic factor was required to “activate” the breakage of chromosome 9 at the Ds locus. Thus, McClintock called this second factor Ac (for Activator).

McClintock began to suspect that Ac and Ds were actually mobile genetic elements when she found it impossible to map Ac. In some plants, it mapped to one position; in other plants of the same line, it mapped to different positions. As if this variable mapping were not enough of a curiosity, rare kernels with dramatically different phenotypes could be derived from the original strain that had frequent breaks in chromosome 9. One such phenotype was a rare colorless kernel containing pigmented spots.

Figure 15-3 compares the phenotype of the chromosome-breaking strain with the phenotype of one of these derivative strains. For the chromosome-breaking strain, a chromosome that breaks at or near Ds loses its end containing wild-type alleles of the C, Sh, and Wx genes. In the example shown in Figure 15-3a, a break occurred in a single cell, which divided mitotically to produce the large sector of mutant tissue (c sh wx). Breakage can happen many times in a single kernel, but each sector of tissue will display the loss of expression of all three genes. In contrast, each new derivative affected the expression of only a single gene. One derivative that affected the expression of only the pigment gene C is shown in Figure 15-3b. In this example, pigmented spots appeared on a colorless kernel background. Although the expression of C was altered in this strange way, the expression of Sh and Wx was normal and chromosome 9 no longer sustained frequent breaks.

To explain the new derivatives, McClintock hypothesized that Ds had moved from a site near the centromere into the C gene located close to the telomeric end. In its new location, Ds prevents the expression of C. The inactivation of the C gene explains the colorless parts of the kernel, but what explains the appearance of the pigmented spots? The spotted kernel is an example of an unstable phenotype. McClintock concluded that such unstable phenotypes resulted from the movement or transposition of Ds away from the C gene. That is, the kernel begins development with a C gene that has been mutated by the insertion of Ds. However, in some cells of the kernel, Ds leaves the C gene, allowing the mutant phenotype to revert to wild type and produce pigment in the original cell and in all its mitotic descendants. There are big spots of color when Ds leaves the C gene early in kernel development (because there are more mitotic descendants), whereas there are small spots when Ds leaves the C gene later in kernel development. Unstable mutant phenotypes that revert to wild type are a clue to the participation of mobile elements.

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What is the relation between Ac and Ds? How do they interact with genes and chromosomes to produce these interesting and unusual phenotypes? These questions were answered by further genetic analysis. Interactions between Ds, Ac, and the pigment gene C are used as an example in Figure 15-4. There, Ds is shown as a piece of DNA that has inactivated the C gene by inserting into its coding region. The allele carrying the insert is called c-mutable(Ds), or c-m(Ds) for short. A strain with c-m(Ds) and no Ac has colorless kernels because Ds cannot move; it is stuck in the C gene. A strain with c-m(Ds) and Ac has spotted kernels because Ac activates Ds in some cells to leave the C gene, thereby restoring gene function. The leaving element is said to excise from the chromosome or transpose.

Other strains were isolated in which the Ac element itself had inserted into the C gene [called c-m(Ac)]. Unlike the c-m(Ds) allele, which is unstable only when Ac is in the genome, c-m(Ac) is always unstable. Furthermore, McClintock found that, on rare occasions, an allele of the Ac type could be transformed into an allele of the Ds type. This transformation was due to the spontaneous generation of a Ds element from the inserted Ac element. In other words, Ds is, in all likelihood, an incomplete, mutated version of Ac itself.

Several systems like Ac/Ds were found by McClintock and other geneticists working with maize. Two other systems are Dotted [(Dt), discovered by Marcus Rhoades] and Suppressor/mutator [(Spm), independently discovered by McClintock and Peter Peterson, who called it Enhancer/Inhibitor (En/In)]. In addition, as you will see in the sections that follow, elements with similar genetic behavior have been isolated from bacteria, plants, and animals.

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The common genetic behavior of these elements led geneticists to propose new categories for all the elements. Ac and elements with similar genetic properties are now called autonomous elements because they require no other elements for their mobility. Similarly, Ds and elements with similar genetic properties are called nonautonomous elements. An element family is composed of one or more autonomous elements and the nonautonomous members that can be mobilized. Autonomous elements encode the information necessary for their own movement and for the movement of unlinked nonautonomous elements in the genome. Because nonautonomous elements do not encode the functions necessary for their own movement, they cannot move unless an autonomous element from their family is present somewhere else in the genome.

Figure 15-5 shows an example of the effects of transposons in a rose.

Although geneticists accepted McClintock’s discovery of transposable elements in maize, many were reluctant to consider the possibility that similar elements resided in the genomes of other organisms. Their existence in all organisms would imply that genomes are inherently unstable and dynamic. This view was inconsistent with the fact that the genetic maps of members of the same species were the same. After all, if genes can be genetically mapped to a precise chromosomal location, doesn’t this mapping indicate that they are not moving around?

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Because McClintock was a highly respected geneticist, her results were not questioned. Rather, their relevance to other organisms was questioned by others who argued that maize is not a natural organism: it is a crop plant that is the product of human selection and domestication. This view was held by some until the 1960s, when the first transposable elements were isolated from the E. coli genome and studied at the DNA-sequence level. Transposable elements were subsequently isolated from the genomes of many organisms, including Drosophila and yeast. When it became apparent that transposable elements are a significant component of the genomes of most and perhaps all organisms, Barbara McClintock was recognized for her seminal discovery by being awarded the 1983 Nobel Prize in Medicine or Physiology.