In the middle of the last century, Barbara McClintock, an American researcher, discovered amazing genes in corn that were able, on their own, to change their position on chromosomes. Today they are called “jumping genes”, or “transposable (mobile) elements”. This discovery was not recognized for a long time or was regarded at best as a unique phenomenon characteristic of corn alone. However, it was this discovery that brought McClintock the Nobel Prize of 1983 — today jumping genes are found in virtually all the animal and plant species.
So where do they spring from, these jack-in-the-box genes, what are they doing in the cell, and are they of any use? Why can a family of a fruit fly with genetically healthy parents produce mutant progeny because of these jumping genes or can even appear infertile? What is the role of jumping genes in the evolution?
Note that the genes responsible for the operation of cells are arranged in chromosomes in definite order. Consequently, the so-called genetic maps have been constructed for many unicellular and multicellular organisms. However, the amount of genetic material located between the genes is by an order of magnitude larger as compared with the genetic material in the genes proper. The role this ballast DNA fraction plays is yet to be finally clarified; however, mobile elements are most frequently detectable in this particular DNA fraction. Moreover, not only do they migrate themselves, but can also grab the neighboring DNA fragments.
What is the origin of jumping genes? It is assumed that at least some of them descend from viruses since certain mobile elements are capable of forming virus particles like, for example, the mobile element gipsy of the fruit fly Drosophila melanogaster. Some mobile elements appear in the genome owing to a horizontal transfer. For example, the mobile hobo element of Drosophila melanogaster has repeatedly inserted itself anew into the genome of this species. Some researchers think that certain DNA regulatory regions also display autonomy and an inclination to “wander”.
On the face of it, jumping genes seem “egotists” or even “parasites”, especially if we take into account the fact that they carry information about protein structures that are necessary exclusively for their own transposition. Therefore, it may seem that the main function of mobile elements is their self-preservation via reproduction.
On the other hand, the majority of jumping genes sit still despite their name, though they constitute one-fifth of the genetic material of Drosophila melanogaster and almost half of the human genome.
The above-mentioned redundancy of DNA has an advantage: the ballast DNA (inactive mobile elements included) stands against the foreign DNA in case it enters the genome. The probability that a new element will insert itself into a useful gene, thereby impairing its operation, decreases drastically if the amount of ballast DNA is considerably larger than that of meaningful DNA.
A certain redundancy of DNA is as beneficial as the superfluity of letters in words: we write “I am going to,” yet say “I’m gonna.” Part of the sounds is inevitably lost; however, the meaning is retained due to the redundancy of sounds. The same principle works at the level of individual amino acids in the molecule of an enzyme protein: only the amino acid sequence that forms the enzyme’s active center is strictly conserved. Thus, redundancy at various levels is a sort of buffer that guarantees the stability of the system. In a similar way, the mobile elements that have lost their mobility do not become useless for the genome. As they say half a loaf is better than no bread.
The mobile elements that have retained the ability to jump travel from one drosophila chromosome to another at a frequency of 10-2–10-5 per gene per generation depending on the type of element, particular genetic background, and ambient conditions. This means that one of a hundred to thousand jumping genes present in the cell changes its location after another cell division. As a result, the arrangement of mobile elements along the chromosome may alter essentially several generations later.
It is convenient to study these arrangements using polytene (multistrand) chromosomes from the salivary glands of drosophila larvae. These chromosomes are much thicker than ordinary chromosomes, which considerably simplifies their microscopic examination. How do such chromosomes come into being? The DNA of each chromosome in the cells of salivary glands multiplies as if it were an ordinary cell division; however, the cell itself does not divide. Consequently, the number of cells in the gland remains the same, whereas up to several thousand identical DNA strands accumulate in each chromosome over 10–11 reproduction cycles.
The jumping genes of drosophila have been studied better than those of other multicellular organisms, partly thanks to polytene chromosomes. These studies have demonstrated that it is difficult to find two individuals displaying an identical arrangement of mobile elements even within the same population of fruit flies. Thus, there are solid grounds to believe that the majority of spontaneous mutations in drosophila are caused by the migration of these “jumpers”.
The consequences may depend…
As for their effect on the genome, mobile elements may be divided into several groups. Some elements perform the functions that are exclusively important and useful for the genome. For example, the telomeric DNA, located at the ends of drosophila chromosomes, consists of specific mobile elements. This DNA is extremely important: its loss leads to the loss of the entire chromosome during cell division and, as a result, to the cells’ death.
Other mobile elements are obvious “saboteurs”. At least, they are regarded as such now. For example, mobile elements from class R2 can specifically insert themselves into the genes of arthropods that code for a protein of ribosomes, cell “factories” that synthesize proteins. Individuals with such abnormalities survive only because of the presence of multiple copies of such genes in each cell genome.
There are mobile elements that migrate only in reproductive tissues, that is the tissues that produce sexual cells. This is due to the fact that in different tissues the same mobile element is able to produce molecules of enzyme protein necessary for migration which differ in their length and function.
An example of such mobile elements is the P element of Drosophila melanogaster, which appeared in the natural populations of this fly owing to a horizontal transfer from other drosophila species not earlier than one hundred years ago. At present, however, there is no population of Drosophila melanogaster on the Earth where P element is absent. It should be mentioned that the major part of its copies is defective; moreover, the same defective version is found virtually everywhere. The role of this version in the genome is peculiar: it is “intolerant” to its “kinfolk” and plays the role of repressor that blocks their migration. Thus, the genome of drosophila can be partially protected against the jumps of an “alien” by its own derivatives.
The point is to choose proper parents!
The main part of the jumps of mobile elements has no effect on the outward appearance of the fly as they occur in the ballast DNA; yet the activity of mobile elements in certain situations increases drastically.
However strange it may seem, the most powerful factor that induces the migration of jumping genes is unsuccessful selection of parents. For example, what will the result be if we cross the females from the laboratory population of Drosophila melanogaster lacking P element (since their ancestors were isolated from a natural population about one hundred years ago) with the males carrying P element? Manifold genetic abnormalities may appear in the hybrids owing to an intensive transposition of the mobile element. This phenomenon, named hybrid dysgenesis, is caused by the fact that the repressor prohibiting the transposition of this mobile element is absent in the maternal cytoplasm.
Thus, if the bridegrooms from population A and brides from population B are able to make families producing numerous progeny, the opposite statement is not always true. A family of genetically sound parents can produce a large number of mutant or sterile progeny or even appear completely infertile if the father and mother have different sets of mobile elements in their genomes. The abnormalities are especially numerous when the experiment is conducted at 29 ° C. The effect of external factors is superimposed onto the genetic background, thereby boosting the effect of genome disparity, although these factors if taken separately (even ionizing radiation) are unable to induce mass migrations of mobile elements.
Similar events may also occur in Drosophila melanogasterwith involvement of other families of mobile elements.
The “mobile” evolution
The cellular genome may be regarded as a certain ecosystem composed of both constant and transient members where the neighbors not only coexist but also interact with one another. The interaction between host genes and mobile elements has not been sufficiently studied so far; however, the results are numerous—from death of the organism due to the damage of an important gene to restoration of the function of its previously damaged regulatory region.
It may happen that jumping genes themselves interact with one another. For example, a phenomenon resembling immunity is known, when a mobile element cannot insert itself in the vicinity of the already present mobile element of the same kind. However, not all mobile elements are so tactful: P elements can, without any ceremony, insert themselves into one another and neutralize the activity of their kindred.
In addition, the genome is capable of self-regulating the number of mobile elements contained. The point is that mobile elements are able to exchange homologous regions with one another—this process is named recombination. As a result of this interaction, mobile elements depending on their orientation can either lose (deletion) or turn (inversion) the fragments of host DNA located between them. If a large enough chromosome fragment is lost, the genome dies. However, inversions or small deletions create a diversity of chromosomes, which is regarded as a necessary condition for evolution.
The recombination between the mobile elements located in different chromosomes generates chromosome rearrangements that can lead to an imbalance of the genome after subsequent cell divisions. And similar to an imbalanced budget, an imbalanced genome encounters certain difficulties when it is divided. Thus, death of unsuccessful genomes is one of the reasons why active mobile elements do not fill chromosomes unlimitedly.
Every Cloud Has a Silver Lining
How large is the contribution of mobile elements to the evolution? First, the majority of mobile elements insert themselves at random; consequently, they can impair or change the structure or regulation of the gene into which they have penetrated. Then natural selection rejects the unsuccessful versions and fixes the successful ones, i. e. those which display adaptive properties.
If the consequences of the mobile element’s insertion are neutral, the population can retain such a variant, thereby providing a certain diversity of the gene’s structure. This may come in handy later, under adverse ambient conditions. Theoretically, mass migration of mobile elements can induce concurrent mutations in many genes, which may appear beneficial when ambient conditions change drastically.
On the other hand, according to modern concepts, changes in gene regulation are considerably more significant for their operation and, presumably, for the evolution of a species than changes in their structure and number. The behavior of mobile elements does not refute this thesis, because the evolutionary position of a species is independent of the number of mobile elements that it has accumulated. Most likely, mobile elements do not cut the mustard in the evolution; however, nobody will dare to state that they are merely parasitic DNA.
Summing up, let’s recall that various mobile elements are abundant in the genome; they are able to interact with both one another and host genes; and they can be harmful or indispensable. The genomic instability caused by migration of mobile elements may end in a tragedy for an individual; however, the ability to change rapidly is a necessary condition for the survival of a population or a species. This creates diversity, which forms the background for natural selection and subsequent evolutionary transformations.
An analogy can be drawn between jumping genes and immigrants: some immigrants or their descendants become full-fledged citizens, others obtain a residence permit, and those who violate the law are deported or imprisoned. Mass migrations of people may rapidly change any country.
Ratner, V. A. and Vasilieva, L. A. Induction of Transpositions of Mobile Genetic Elements by Stress Effects. Russkii pereplet, 2000.
Gvozdev, V. A. Mobile DNA of eukaryotes. Soros Educational Journal, 1998, no. 8.