by Johann de Vries and Wilfried Wackernagel

It is well known that genes are passed on from parent to offspring, i.e. from generation to generation (vertical gene transfer). However, recent research has also shown cases of gene transfer between individuals of the same generation (horizontal gene transfer), even between very different organisms. Spreading "jumping genes" have also been observed - genetic material travelling through the kingdoms of living organisms.

Genes have been on everyone's lips since the debate about genetically modified food. In a literal sense, they always have been: when we eat vegetables, meat, yoghurt, etc., we have always ingested the genes of living beings, i.e. plants, animals, fungi and bacteria. Living organisms consist of cells whose nuclei harbour the genes that make life possible for each organism. They give it its typical and individual characteristics and abilities. In detail, they ensure the development of the organism, the metabolism that builds up the body's own substances from food and provides energy, and they also control behaviour. The entirety of an organism's genes is referred to as its genome. As in bacteria, it can consist of a single chromosome with around 5,000 genes. In higher organisms, however, the genome is made up of several chromosomes. The number of genes in humans is estimated to be around 100,000. The genome is passed on to offspring with the utmost precision (vertical gene transfer).

The key to how genes control, for example, the development of a person from a fertilised egg cell to an adult lies in the sequence of the four gene building blocks (the bases adenine, thymine, cytosine and guanine) in the genetic material (DNA, deoxyribonucleic acid). Based on numerous analyses of the base sequence of genes, it has now become clear that the sequence similarity of genes with the same function is relatively high in organisms that are closely related in terms of developmental history, e.g. humans and mice. In very distantly related organisms, the similarity is very low or not recognisable.

In some cases, however, the sequence analyses have led to highly surprising results. For example, it was found that a gene from a plant also occurs in the intestinal bacterium Escherichia coli. How did the gene get from a chromosome of the plant into the chromosome of the bacterium? Both organisms have no common ancestors in evolution from which they could have inherited the gene. So a gene migration must have taken place here. How is this conceivable? Another finding, which was made years ago and has since been documented in great detail, is the phenomenon of "jumping genes" or transposons. These genetic elements occasionally change their location in the chromosomes of an organism, i.e. they transpose. We now know that such transposons occur in all types of living organisms, including humans. They can be equipped with additional genes and take these with them when they transpose. From this and other examples, the picture that emerges is that mobile hereditary systems and migration pathways for genes have obviously developed in nature. Does nature still utilise these today by organisms incorporating genes into their genome? In genetic engineering, the transplantation of genes from one organism into another is known to be the methodological centrepiece. In fact, we can also follow the migration of genes in nature today in a number of cases, both between organisms of the same species as well as between less related and even unrelated organisms (such as bacteria and plants).

The fruit fly Drosophila melanogaster has been one of the most important objects of genetic research since the 1920s. Since then, fruit flies from many regions of the world have been repeatedly caught and added to the strain collections of research institutes and bred further. A few years ago, a transposon, the so-called P-element, was discovered in newly caught fruit flies. It became a real sensation when it turned out that the flies from the old collections almost never contained the transposon, whereas newly caught animals, from whatever continent, very often had this transposon. A time analysis showed that a worldwide invasion of Drosophila melanogaster populations by the P element had begun in the late 1960s. The epidemic-like spread presumably occurs during fertilisation. If a crossing partner has the transposon, it also jumps over to the transposon-free chromosomes in the offspring, i.e. the offspring then pass the element on to their offspring with a 100% chance. The origin of the element is still unclear. Another, no less surprising pathway for this element has now been revealed. While most of the related fruit fly species that do not mate with D. melanogaster do not have the P element, as expected, two more distant relatives (D. willistoni and D. obscura) have now been found that frequently carry the P element. How did it get into these species or from them into D. melanogaster? Possibly the element was transmitted by a parasite, e.g. a mite that infests all three species of Drosophila. This could mean that genes are also transferred with the transfer of body fluids or cells during the mite bite. Such a gene pathway would generally be conceivable through stinging and sucking insects. The transmission of pathogens in this way has been known for a long time.

Certain bacteria have the amazing ability to insert genes into the cells of higher organisms. The process has been studied in great detail in Agrobacterium tumefaciens. When such a bacterium infects a plant, it triggers the formation of a DNA channel through which the bacteria's genetic material is transported. This finally reaches the nucleus of the plant cell. The bacterial genes now cause the plant cell to divide more frequently (tumour formation) and to produce and release certain nutrients. The bacteria live off these as parasites. Agrobacteria can parasitise numerous, very different plant species in this way. This is a natural case of active horizontal gene transfer from bacteria into higher organisms. This process has been utilised in genetic engineering for several years. The DNA of agrobacteria can be genetically modified in order to introduce specific genes into the cell nucleus of plants. Many of the genetically engineered new varieties of cultivated plants (e.g. certain varieties of rapeseed, potatoes, maize, cloves) have been produced in this way.

Genes that cannot jump and which are apparently not part of an organised gene transfer process as in agrobacteria nevertheless occasionally change organisms. When analysing genetic material, new evidence of this is constantly coming to light, turning sober sequence analysis into highly exciting research. The genome projects, in which the entirety of the genes of a number of bacteria, fungi, plants and also humans are analysed, also help with these investigations. This shows that genes have occasionally passed from plants to bacteria and vice versa, but also from bacteria to animals or from fungi to plants.

If a foreign gene enters a cell, it can either increase the number of genes (addition) or replace existing genes (substitution). Both possibilities can be beneficial for the genetic development of the organism: it receives genetic material that may endow it with new characteristics. The transmission pathways are not yet known. However, some cases suggest that horizontal gene transfer occasionally occurs when organisms live closely together, e.g. between bacteria and fungi in the rumen of cattle or between bacteria and plant cells when the bacteria live inside plants as symbionts.

It was discovered around 50 years ago that bacteria also exchange genes horizontally with each other. In contrast to other living organisms, research into these natural transfer processes in bacteria has already progressed quite far. According to this, genes are transferred in the course of cell-to-cell contacts, similar to the process between agrobacteria and plants. Alternatively, the bacteria actively take up the released genetic material from dead cells and integrate it into their genome. Finally, some viruses can also transfer genes from one cell to another. These processes can be easily reproduced in the test tube under suitable conditions. As part of a larger research project, we have shown that genes can also be transferred in the environment in the form of naked DNA, e.g. between soil bacteria. Even very different bacteria can exchange genetic material.

This leads to an unexpected paradox: some bacterial species have been around for more than 100 million years and have apparently hardly changed despite the possibility of gene exchange. An examination of their genomes shows that they are composed like a mosaic of genes from different origins. It must therefore be assumed that the appropriation of genes is a successful way for an organism to adapt to changing environmental conditions, for example, without losing important basic characteristics. Examples of this can be seen today in many areas of the fight against infectious diseases. Pathogenic bacteria adapt to the use of antibiotics in therapy by "acquiring" antibiotic resistance genes. This is practically unavoidable, as the natural gene transfer processes cannot yet be suppressed. It has been proven that the spread of insensitivity to penicillin, e.g. among the pathogens of gonorrhoea (Neisseria gonorrhoeae) or meningitis (Neisseria meningitidis), and even between the two, occurs through the transfer of resistance genes. The untargeted use of antibiotics creates the selection pressure for the accelerated migration of genes.

Natural gene migration is often seen as one of the risks associated with the release of genetically modified organisms into the environment. If plants, fungi and bacteria were to release their genetic material into the environment, the recombinant DNA could be released into other organisms in an undesirable way. Our own investigations in the context of safety research have shown that DNA from bacteria and plants is indeed released into the environment, survives there and can also be taken up again in bacteria. The transfer pathways demonstrated in this way have presumably been effective for as long as organisms have existed. In this way, it has been possible to "try out" all kinds of genes through gene transfer over billions of years. Genetically engineered DNA is nothing fundamentally new here. In addition, as stated at the beginning, all animals, including humans, absorb genes daily, e.g. with their food, without harm. Even if foreign genetic material were to enter tissue cells, inheritance would not be possible because the path into the germline cells is blocked. In terms of occupational safety, however, the situation is different when researchers work with concentrated preparations of human cancer genes, for example. If these were to enter body cells, it could not be ruled out that the DNA would be incorporated into a cell chromosome and that a tumour could possibly develop from this. Although such a gene transfer could not be proven in animal experiments, the Central Commission for Biological Safety (Berlin) recently issued a precautionary statement on the subject. According to this statement, suitable measures must be taken during laboratory work to prevent the absorption of such DNA into the body (e.g. through skin contact, as a result of injuries or through inhalation).

The horizontal migration of genetic material, in addition to classical parental inheritance, is obviously an important part of life. The astonishing coexistence of high species constancy on the one hand and genome plasticity on the other is a phenomenon full of unanswered questions. In fact, there is still room for new genes in all genomes. Only 5 % of human genetic material is occupied by genes, in plants often less than 0.5 % and in bacteria about 95 %. Due to the possibility of acquiring new genes, gene flow between living organisms is presumably an important factor for adaptation to changing environmental conditions and thus for evolution. The underlying mechanisms and the effects of the individual processes are a fascinating field of research that has been opened up by molecular biology.

The authors

Dr Johann de Vries, 34, studied biology in Bielefeld and Oldenburg. He obtained his doctorate in 1994 under Prof Wackernagel with a thesis on proteins involved in DNA repair and recombination in bacteria. From 1992 to 1994 he was project leader (removal of heavy metals from compost) in the technology pool at Emden University of Applied Sciences. Since 1995 he has been involved in safety research on the release of genetically modified plants, including the development of monitoring procedures for recombinant DNA in the environment.

Prof Dr Wilfried Wackernagel (56) has been teaching genetics in the Department of Biology since 1982. After completing his doctorate, two years of research at Yale University, USA. Habilitation in 1976 at the University of Bochum. His research areas are the molecular mechanisms of genetic recombination, DNA repair and DNA transfer in bacteria, including practical applications. He has been a member of the Central Commission for Biological Safety of the Federal Republic of Germany for five years.