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Horizontal gene transfer (HGT)

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Also listed as: Lateral gene transfer, HGT
Related terms
Background
Methods
Research
Implications
Limitations
Safety
Future research
Author information
Bibliography

Related Terms
  • Biotechnology, conjugation, genetic engineering, gene therapy, HGT, lateral gene transfer, mosaic genes, recombination, somatic gene therapy, therapeutic gene transfer, transduction, transformation, viral vectors.

Background
  • Horizontal gene transfer (HGT), also known as lateral gene transfer, is the process by which genetic material is transferred from one organism to another that is not its offspring. This can occur naturally, for example, when bacteria transfer deoxyribonucleic acid (DNA) to other bacteria, or through other mechanisms such as a viral vector, a tool used in biology to deliver genetic material into cells in order to produce genetically altered organisms.
  • HGT was first described in bacteria, when a scientist observed that antibiotic resistance could be transferred between different species of bacteria. This phenomenon occurs when one bacterial cell becomes resistant to an antibiotic, and can easily transfer these resistance genes to other species of bacteria. Although most frequent in bacteria, HGT also occurs naturally in viruses, plants, insects, and even between bacteria and fungi.
  • The rate at which HGT occurs in nature is relatively low despite the number of opportunities that exist for it to occur, because organisms have built-in features that prevent HGT from happening. These mechanisms include a cell wall, which prevents material from entering or exiting the cell unless certain conditions are met, and enzymes that will break down any DNA that enters the cell. Cells also have mechanisms that prevent foreign DNA from being incorporated into their native DNA.
  • Artificial applications of HGT include forms of genetic engineering that result in an organism that has had its genes changed in some way, allowing for new structures or functions. These applications are particularly useful for gene therapy, an experimental procedure that may help treat or prevent genetic disorders and some types of cancer. Gene therapy is being studied as a possible way to either replace or inactivate a mutated gene that is causing a disorder. Other gene therapy studies involve inserting a new gene to help the body fight against a specific disease.
  • In some cases, this transfer of genetic material allows the cell to better adapt to its environment and thus improve its chance of survival. This tends to be the case in genetically engineered crops in which a crop's genes are altered to produce plants with more desirable characteristics or to make new species. The success of transferring genetic material into a new cell depends on whether the transferred DNA provides enough advantage to the cell to make recombination worthwhile.

Methods
  • Horizontal gene transfer (HGT) can occur in a variety of ways. One way is through transformation, which involves the introduction, uptake, and expression of foreign genetic material that is, DNA or ribonucleic acid (RNA). Transformation is fairly common in bacteria and less common in higher organisms. This method is also used in medical and industrial approaches of genetic engineering. Transformation occurs rarely in nature as a result of various protective mechanisms built in to the cell, including the cell wall, the presence of enzymes to break down any foreign DNA that enters the cell, and the ability to prevent the foreign DNA from being incorporated into its own DNA. During transformation, only short DNA fragments are typically exchanged and can involve any part of a chromosome, as long as an entire gene is transferred and not just a piece of a gene. This process is most common among bacteria that are naturally transformable.
  • When genetic material from one organism is successfully incorporated into a cell of another organism, from the same or different species, the resulting genes are known as mosaic genes. Mosaic genes are the same as other cells from the original species except for any polymorphisms, or variations, that have been acquired from the donor cell.
  • Often this new sequence can act as a genetic marker, or a sequence of DNA that is indicative of a particular genetic trait, such as antibiotic resistance. Examples of well-known mosaic genes include those that encode for resistance to penicillin, such as the bacteria Streptococcus pneumoniae.
  • Another way in which HGT can occur is through conjugation. In conjugation, two cells must be in close contact, fuse together for a period of time, and then the donor cell must transfer its genetic material into the recipient cell. This process differs from transformation because in transformation, there is no cell-to-cell contact, and instead of exchanging short DNA fragments, long fragments are exchanged.
  • Transduction is a third way in which HGT can occur. This is the transfer of DNA from one bacterium to another through a virus known as a viral vector. This process is commonly used by biologists to effectively introduce a foreign piece of DNA into a host cell's genome.
  • Horizontal gene transfer can also occur through bacteriophage transduction, in which a bacteriophage, a virus that infects bacteria, is used to infect a bacterium. This infected cell then uses its own cell machinery to make more viruses.
  • Each of these methods can introduce DNA that is not like the DNA of the recipient cell. If there are similarities between the donor and the recipient cell, the genetic material may be incorporated through a process known as recombination. Recombination occurs when pieces of DNA are incorporated into another DNA molecule. In other cases of DNA transfer, the recipient cell may require another piece of DNA from another cell in order to properly incorporate the DNA from the donor cell. In some cases, this transfer of genetic material allows the cell to better adapt to its environment and therefore improves its chances of survival.
  • Horizontal gene transfer is also used to deliver genes into plants and animals, including humans. Viral vectors, which are viruses that include a piece of foreign DNA but do not have the machinery to infect, are used to combine two different sets of DNA together. Viral vectors containing antigens, which are substances that induce an immune response, are used as vaccines; these are called DNA vaccines. The hepatitis B vaccine is an example of a DNA vaccine that has been tested in humans.
  • Non-viral, vector-based approaches are also used for HGT in plants and animals. These include microinjection, the direct injection of DNA or RNA. Another form of HGT is nuclear transfer, a form of cloning. During nuclear transfer, the DNA from an unfertilized egg is removed and the nucleus of a donor cell, which contains DNA, is injected into the egg. This is an example of large-scale gene transfer in which all of the genetic material from one organism (the donor cell) is injected into another cell (the recipient cell). Liposomes, which are small, fluid-filled pouches with walls made up of the same substances that as the cell membrane, are also used to carry normal genes into a cell in order to replace defective genes. This is a type of gene therapy.

Research
  • Natural horizontal gene transfer (HGT) was first identified in bacteria. Scientists observed that the genetic material from one bacterium could be transferred to another that was not its offspring. Horizontal gene transfer is thought to be the cause of drug-resistant strains of bacteria; one bacterium that gained the ability to resist an antibiotic transferred its genes to another and so on, resulting in many bacteria that can no longer be killed by antibiotics.
  • Current research in the area of HGT aims to develop databases and algorithms that will be useful in identifying all transferable DNA sequences and their mechanisms of transfer.
  • Research is also focusing on identifying how the process of horizontal gene transfer is regulated within the recipient cell. Much of the scientific research on HGT has focused on Escherichia coli and Salmonella, which are relatively closely related and have successfully transferred genetic material back and forth over time.
  • Gene therapy: Gene therapy is an experimental procedure that may help treat or prevent inherited disorders and some types of cancer. There are several different methods of gene therapy that are currently being studied. Gene therapy is being studied as a possible way to either replace or inactivate a mutated gene that is causing a disorder. Other gene therapy studies involve inserting a new gene to help the body fight against a specific disease.
  • No gene therapy products that introduce genetic material into the body have been approved for sale in the United States. Currently, gene therapy is only available through clinical trials. Gene therapy is a growing area of research, and hundreds of trials are ongoing.
  • Cloning: Nuclear transfer, a form of cloning in which the DNA from an unfertilized egg is removed and the nucleus of a donor cell is injected into the egg. This technique has been used to clone a variety of organisms, including tadpoles, mice, sheep, monkeys, cattle, cats, and horses. Cloning human beings has not been performed and is illegal in many countries.
  • Genetic engineering: Much research has been conducted using genetic engineering. Gene knockout experiments use mice with a missing gene in order to study the gene's function by its absence. This technique allows the researcher to examine what effect a certain mutation has on behavior. Similarly, the opposite experiment can be conducted, in which a certain gene is increased within an animal and behavior is monitored for any effects this mutation may have. Human genetic engineering may be used to treat genetic diseases. The first clinical trial of genetic engineering in humans began in 1990, and as of 2008, it is still experimental. This trial involved individuals with severe combined immunodeficiency (SCID); gene therapy is being used as an alternative to bone marrow transplantation to treat these patients.

Implications
  • Antibiotic resistance: Horizontal gene transfer (HGT) was first discovered in bacteria. It is thought that HGT is the cause of drug-resistant strains of bacteria; one bacterium that gained the ability to resist an antibiotic transferred its genes to another and so on, resulting in many bacteria that can no longer be killed by antibiotics. This situation could result in an inability to fight bacterial infections with antibiotics, the only known effective drugs. Some examples of this already exist. Methicillin-resistant Staphylococcus aureus (MRSA) is a strain of Staphylococcus that has become resistant to a number of antibiotics that are typically used to treat severe and potentially life-threatening infections in humans. Another example is multi-drug-resistant tuberculosis, which has become resistant to the two most effective tuberculosis-fighting drugs.
  • Genetically modified foods (GMFs): Since the 1990s, scientists have been able to change the genetic makeup of plants and animals used for human consumption. These food products are called genetically modified foods (GMFs), or genetically modified organisms (GMOs). GMFs are produced to enhance or improve the organism's natural traits. In order to produce GMFs, scientists combine genes from different organisms through a process called recombinant DNA technology. For instance, researchers have added genes to plants, such as corn, to make them more nutritious or resistant to insects.
  • Crops, including rice, corn, soybeans, sweet potatoes, apples, tomatoes, cantaloupes, and other fruits and vegetables, have been genetically modified to improve taste and quality (including color and size), reduce maturation time, increase nutritional content, and increase tolerance to extreme temperatures, as well as to improve resistance to disease, pests, and herbicides.
  • Therapeutic gene transfer: Therapeutic gene transfer or gene therapy is an experimental procedure that may help treat or prevent inherited disorders and some types of cancer. Researchers hope that gene therapy can be used in the future instead of medications or surgery to treat or prevent incurable inherited disorders. Scientists also hope that gene therapy can prevent the growth of cancerous tumors and help wipe out cancer that has already developed.
  • Gene therapy has been suggested as a possible treatment for many inherited disorders and various cancers, and is a growing area of research with hundreds of trials underway.
  • Gene therapy has also been studied as a possible treatment for Parkinson's disease, a degenerative nervous system disease. Researchers have recently figured out a way to transfer genes into the brain. Viruses cannot be used as vectors because they are too big to cross the blood-brain barrier, the protective membrane that separates circulating blood from brain cells. So instead of using viral vectors, researchers have used liposomes, fat molecules coated in the polymer polyethylene glycol (PEG), to deliver the new genes. This allows billions of copies of a gene to be inserted into the brain to calm overactive connections in the brain. Researchers are hopeful that this method may be an effective treatment for Parkinson's disease in the future.

Limitations
  • For horizontal gene transfer (HGT) to occur, the DNA being transferred cannot contain only a piece of a gene, it must contain the entire gene. HGT is often prevented when a cell rejects the transferred genetic material, so the DNA being transferred must be able to survive in the new cell.
  • The potential for negative effects of horizontal gene transfer (HGT) depends on the ability of the genetic material to function in the recipient cell. It also depends on the number of cells into which the new material has been incorporated, which is determined by the rate of HGT, the nature of the gene, and especially environmental influences. If the new genetic material makes functioning difficult, any organism that inherits it will not survive and the new genetic material will no longer exist in that species. If it offers some competitive advantage, it will be passed on to offspring, offering the next generation a similar advantage. This could result in new traits for that species if the genetic material continues to be passed on successfully from generation to generation.
  • Although genetic engineering in the form of gene therapy is being studied in a variety of human trials, some aspects of HGT have not been conducted in humans, such as cloning, most likely because of the scientific and ethical limitations.

Safety




Future research
  • Therapeutic gene transfer or gene therapy is an experimental procedure that may help treat or prevent inherited disorders and some types of cancer. Researchers hope that gene therapy can be used instead of medications or surgery to treat or prevent incurable inherited disorders. Scientists also hope that gene therapy can prevent the growth of cancerous tumors and help wipe out cancer that has already developed.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
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  3. Delorme C, Poyart C, Ehrlich SD, et al. Extent of horizontal gene transfer in evolution of Streptococci of the Salivarius group. J Bacteriol 2007;189(4)1330-1341.
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