# Exogenous DNA

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{{Short description|DNA originating from outside an organism}}
thumb|261x261px|Exogenous DNA strands (Red and Green) shown inside a cell's nucleus.
'''Exogenous DNA''' is [DNA](/source/DNA) originating outside the organism of concern or study.<ref>{{Cite web|title=Exogenous DNA definition|url=https://groups.molbiosci.northwestern.edu/holmgren/Glossary/Definitions/Def-E/Exogenous_DNA.html|access-date=2021-11-20|website=groups.molbiosci.northwestern.edu}}</ref> Exogenous DNA can be found naturally in the form of partially degraded fragments left over from dead cells. These DNA fragments may then become integrated into the chromosomes of nearby bacterial cells to undergo [mutagenesis](/source/mutagenesis).<ref>{{cite book |last1=Hakansson |first1=Anders P. |last2=Marks |first2=Laura R. |last3=Roche-Hakansson |first3=Hazeline |title=Streptococcus Pneumoniae |chapter=Pneumococcal Genetic Transformation During Colonization and Biofilm Formation |date=2015 |pages=129–142 |doi=10.1016/B978-0-12-410530-0.00007-7 |isbn=978-0-12-410530-0 }}</ref> This process of altering bacteria is known as [transformation](/source/Transformation_(genetics)).<ref name=":04" /> Bacteria may also undergo artificial transformation through chemical and biological processes. The introduction of exogenous DNA into eukaryotic cells is known as [transfection](/source/transfection).<ref name=":1">{{Cite web|date=2009-02-13|title=Dorlands Medical Dictionary:transfection|url=http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp?pg=/ppdocs/us/common/dorlands/dorland/eight/000110186.htm|access-date=2021-11-20|archive-url=https://web.archive.org/web/20090213212224/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp?pg=/ppdocs/us/common/dorlands/dorland/eight/000110186.htm|archive-date=2009-02-13}}</ref> Exogenous DNA can also be artificially inserted into the genome, which revolutionized the process of genetic modification in animals. By microinjecting an artificial [transgene](/source/transgene) into the nucleus of an animal embryo, the exogenous DNA is allowed to merge the cell's existing DNA to create a genetically modified, transgenic animal.<ref name=":0">{{cite book |last1=Pritchett-Corning |first1=Kathleen R. |last2=Landel |first2=Carlisle P. |title=Laboratory Animal Medicine |chapter=Genetically Modified Animals |date=2015 |pages=1417–1440 |doi=10.1016/B978-0-12-409527-4.00032-8 |isbn=978-0-12-409527-4 }}</ref> The creation of transgenic animals also leads into the study of altering sperm cells with exogenous DNA.<ref name=":2" />

== History ==
In 1928, bacteriologist [Fredrick Griffith](/source/Frederick_Griffith) observed exogenous DNA alongside bacterial transformation in the species ''[Streptococcus pneumoniae](/source/Streptococcus_pneumoniae)''.<ref>{{cite journal |last1=Griffith |first1=Fred |title=The Significance of Pneumococcal Types |journal=Journal of Hygiene |date=January 1928 |volume=27 |issue=2 |pages=113–159 |doi=10.1017/s0022172400031879 |pmid=20474956 |pmc=2167760 }}</ref><ref name=":04">{{cite thesis |last1=Farley |first1=George |title=Transformation of mammalian cells by exogenous DNA |date=May 1969 |url=https://digitalcommons.unmc.edu/mdtheses/85/ |pages=3–8 }}</ref> In further tests, physician [Oswald Avery](/source/Oswald_Avery) was able to isolate and confirm that the DNA used in the experiment originated from outside the cell and integrated itself into the cell's genome. Repeated experiments proved exogenous DNA integration was possible in other species of bacteria, prompting studies to extend to mammal cells.<ref name=":04" /> The technology for the injection of exogenous DNA into organisms was discovered by Lin in 1966. He was able to use a fine glass needle to insert laboratory-produced DNA into mouse zygotes without breaking their nuclei. In 1976, the first successful delivery of exogenous DNA into mice was performed by Jaenisch using the Moloney leukemia virus.<ref name=":0" />

== Applications ==

=== Transformation ===
The integration of exogenous DNA with the genome of a cell is called [transformation](/source/Transformation_(genetics)) ([transfection](/source/transfection) in animal cells).<ref name=":04" /><ref name=":05" /> Transformation is a naturally occurring process in bacteria. To successfully take up exogenous DNA, bacteria need to be in a state of [competence](/source/Competence_(biology)). Some bacteria are naturally competent, but usually only for a brief time at a certain stage of their growth cycle.<ref>{{cite journal |last1=Chen |first1=Inês |last2=Dubnau |first2=David |title=DNA uptake during bacterial transformation |journal=Nature Reviews Microbiology |date=March 2004 |volume=2 |issue=3 |pages=241–249 |doi=10.1038/nrmicro844 |pmid=15083159 }}</ref> Bacteria can also be made competent through a variety of chemical treatments. These treatments typically involve making the targeted cell membrane more permeable towards accepting exogenous DNA, one such example being exposing the bacteria to a calcium ion solution, or a mixture of [polyethylene glycol](/source/polyethylene_glycol) and [dimethylsulfoxide](/source/dimethylsulfoxide).<ref>{{cite book |last1=Wertz |first1=John E. |last2=Low |first2=K. Brooks |title=Reference Module in Biomedical Sciences |chapter=Genetics, Microbial (General) ☆ |date=2017 |doi=10.1016/B978-0-12-801238-3.99206-7 |isbn=978-0-12-801238-3 }}</ref> Another treatment method is the utilization of electricity ([electroporation](/source/electroporation) or electro transformation) to create holes in the cell membrane for the DNA to enter. Finally, [liposome-mediated](/source/Liposome) transformation can be used. The cell surface and the incoming DNA are both negatively charged, so the DNA is coated with lipids. By shielding the DNA and possibly merging with the membrane lipids, these liposomes can facilitate the entry of DNA.<ref name=":05">{{cite web |title=Introduction to Competent Cell Transformation - US |url=https://www.thermofisher.com/us/en/home/life-science/cloning/cloning-learning-center/invitrogen-school-of-molecular-biology/molecular-cloning/transformation/competent-cell-basics.html |website=Thermo Fisher Scientific }}</ref>

Transformation of bacteria, plant cells and animal cells has important research and commercial functions. Targeted introduction of exogenous DNA is used to identify genes because the introduced DNA can cause a mutation or alter the expression of the targeted gene, providing a unique identifying signal. This technology, known as insertion mutagenesis, often employs [retrovirus](/source/retrovirus)es as the vectors of DNA delivery. Such insertion mutagenesis has been often used to identify many [oncogene](/source/oncogene)s in specific locations in tumor cells.<ref>{{cite journal |last1=Uren |first1=A G |last2=Kool |first2=J |last3=Berns |first3=A |last4=van Lohuizen |first4=M |title=Retroviral insertional mutagenesis: past, present and future |journal=Oncogene |date=21 November 2005 |volume=24 |issue=52 |pages=7656–7672 |doi=10.1038/sj.onc.1209043 |pmid=16299527 }}</ref>

=== Transfection ===
Transfection is the process of introducing exogenous DNA into eukaryotic cells.<ref>{{Cite MeSH |uid=D014162 |name=Transfection}}</ref> It is a more specific term for animal cells, as the process of carcinogenesis in these cells is also included in the definition of transformation. Typically, transfection describes the changes in a cell's genome due to the introduction of foreign DNA.<ref name=":1" /> There are several ways of conducting artificial transfection. Chemical methods involve using chemicals as carriers to introduce DNA, such as calcium phosphate [precipitation](/source/Precipitation_(chemistry)), [DEAE](/source/DEAE)-dextran complexation and lipid-mediated DNA transfer.<ref>{{cite journal |last1=Jordan |first1=M. |last2=Schallhorn |first2=A. |last3=Wurm |first3=F. M. |title=Transfecting Mammalian Cells: Optimization of Critical Parameters Affecting Calcium-Phosphate Precipitate Formation |journal=Nucleic Acids Research |date=February 1996 |volume=24 |issue=4 |pages=596–601 |doi=10.1093/nar/24.4.596 |pmid=8604299 |pmc=145683 }}</ref> Physical methods use techniques such as [electroporation](/source/electroporation), [microinjection](/source/microinjection), and [cell squeezing](/source/CellSqueeze) to increase the permeability of the cell membrane for accepting DNA.<ref>{{cite journal |last1=Sharei |first1=Armon |last2=Zoldan |first2=Janet |last3=Adamo |first3=Andrea |last4=Sim |first4=Woo Young |last5=Cho |first5=Nahyun |last6=Jackson |first6=Emily |last7=Mao |first7=Shirley |last8=Schneider |first8=Sabine |last9=Han |first9=Min-Joon |last10=Lytton-Jean |first10=Abigail |last11=Basto |first11=Pamela A. |last12=Jhunjhunwala |first12=Siddharth |last13=Lee |first13=Jungmin |last14=Heller |first14=Daniel A. |last15=Kang |first15=Jeon Woong |last16=Hartoularos |first16=George C. |last17=Kim |first17=Kwang-Soo |last18=Anderson |first18=Daniel G. |last19=Langer |first19=Robert |last20=Jensen |first20=Klavs F. |title=A vector-free microfluidic platform for intracellular delivery |journal=Proceedings of the National Academy of Sciences |date=5 February 2013 |volume=110 |issue=6 |pages=2082–2087 |doi=10.1073/pnas.1218705110 |pmid=23341631 |bibcode=2013PNAS..110.2082S |doi-access=free |hdl=1721.1/80382 |hdl-access=free }}</ref> Viral methods (or [transduction](/source/Transduction_(genetics))) use recombinant, lab manipulated viruses as vectors to alter embryos and sperm cells.<ref name=":05" />

=== Transgenesis ===
The use of exogenous DNA to transform cells has spawned the discipline of [transgenesis](/source/transgenesis): the use of recombinant DNA techniques to introduce new characters into organisms, mainly through transgenes.<ref>{{cite book |last1=Blanco |first1=Antonio |last2=Blanco |first2=Gustavo |title=Medical Biochemistry |chapter=The Genetic Information (II) |date=2017 |pages=493–524 |doi=10.1016/B978-0-12-803550-4.00022-7 |isbn=978-0-12-803550-4 |quote=Transgenesis refers to the process of introducing an exogenous or modified gene (transgene) into a recipient organism of the same or different species from which the gene is derived. The transgene becomes incorporated into the genome of the host organism and can be transmitted to the offspring. }}</ref>  A transgene is an introduced DNA segment that be used to encode a gene in its host animal.<ref>{{cite book |last1=Costantini |first1=F. |title=Brenner's Encyclopedia of Genetics |chapter=Transgenic Animals |date=2001 |pages=117–123 |doi=10.1016/B978-0-12-374984-0.01560-6 |isbn=978-0-08-096156-9 }}</ref> Biologists uses transgenesis as a tool to breed genetically modified, or transgenic animals that provide a wide range of uses. These include the study of developmental genetics, disease processes and [gene regulation](/source/Regulation_of_gene_expression).<ref>{{cite book |last1=De Windt |first1=Leon J. |last2=Doevendans |first2=Pieter A. |last3=Chien |first3=Kenneth R. |title=Molecular Basis of Cardiovascular Disease |chapter=Generation and Cloning of Genetically Modified Animals |date=1999 |pages=49–71 |doi=10.1016/B978-0-7216-9428-3.50009-3 |isbn=978-0-72-169428-3 }}</ref> For example, transgenic farm animals can produce human pharmaceuticals alongside increased milk or meat production. Tissues and organs from transgenic animals can also be used in transfusions and transplants with a lesser chance of immune rejection.<ref>{{cite book |last1=Costantini |first1=F. |title=Brenner's Encyclopedia of Genetics |chapter=Transgenic Animals |date=2001 |pages=117–123 |doi=10.1016/B978-0-12-374984-0.01560-6 |isbn=978-0-08-096156-9 }}</ref>

=== Sperm cells ===
Using transgenesis to genetically modify animals has spawned a new division of using exogenous DNA to modify [sperm cells](/source/sperm_cells). Epididymal sperm cells were shown to react to exogenous nucleic acids, allowing for DNA to reversibly bind to the spermatozoa through ionic interactions.<ref>{{cite journal |last1=Lavitrano |first1=M. |last2=French |first2=D. |last3=Zani |first3=M. |last4=Frati |first4=L. |last5=Spadafora |first5=C. |title=The interaction between exogenous DNA and sperm cells |journal=Molecular Reproduction and Development |date=March 1992 |volume=31 |issue=3 |pages=161–169 |doi=10.1002/mrd.1080310302 |pmid=1554501 }}</ref> The ability of sperm cells to locate and internalize exogenous DNA was then used to transfer foreign genes into an oocyte during fertilization to create transgenic animals.<ref name=":2">{{cite book |last1=Lavitrano |first1=Marialuisa |last2=Giovannoni |first2=Roberto |last3=Cerrito |first3=Maria Grazia |title=Spermatogenesis |chapter=Methods for Sperm-Mediated Gene Transfer |series=Methods in Molecular Biology |date=2013 |volume=927 |pages=519–529 |doi=10.1007/978-1-62703-038-0_44 |pmid=22992941 |isbn=978-1-62703-037-3 }}</ref> However, a low efficiency rate hinders this technique due to the low uptake of exogenous DNA by sperm cells compounded with the low fertilization rate of the oocyte.<ref>{{cite journal |last1=García-Vázquez |first1=Francisco Alberto |last2=Ruiz |first2=Salvador |last3=Grullón |first3=Luis Alberto |last4=Ondiz |first4=Aitor de |last5=Gutiérrez-Adán |first5=Alfonso |last6=Gadea |first6=Joaquín |title=Factors affecting porcine sperm mediated gene transfer |journal=Research in Veterinary Science |date=December 2011 |volume=91 |issue=3 |pages=446–453 |doi=10.1016/j.rvsc.2010.09.015 |pmid=20980036 }}</ref>

== See also ==
* [Mutagenesis](/source/Mutagenesis)
* [Transfection](/source/Transfection)
* [Transduction](/source/Transduction_(genetics))
* [Gene Transfer](/source/Gene_transfer)
* [Sperm-mediated gene transfer (SMGT)](/source/Sperm-mediated_gene_transfer)
* [Horizontal gene transfer](/source/Horizontal_gene_transfer)

== References ==
{{Reflist}}

Category:DNA

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Adapted from the Wikipedia article [Exogenous DNA](https://en.wikipedia.org/wiki/Exogenous_DNA) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Exogenous_DNA?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.