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{{short description|Type of mutation on somatic cell}}
{{Distinguish|Somatic hypermutation}}

A '''somatic mutation''' is a change in the [[Nucleic acid sequence|DNA sequence]] of a [[somatic cell]] of a [[multicellular organism]] with dedicated [[Germline|reproductive cells]]; that is, any [[mutation]] that occurs in a cell other than a [[gamete]], [[germ cell]], or [[gametocyte]]. Unlike [[germline mutation]]s, which can be passed on to the descendants of an organism, somatic mutations are not usually transmitted to descendants. This distinction is blurred in plants, which lack a dedicated [[germline]], and in those animals that can [[Asexual reproduction|reproduce asexually]] through mechanisms such as [[budding]], as in members of the cnidarian [[Hydra (genus)|genus ''Hydra'']].

While somatic mutations are not passed down to an organism's offspring, somatic mutations will be present in all descendants of a cell within the same organism. Many [[cancer]]s are the result of accumulated somatic mutations.

== Fraction of cells affected ==
{{CSS image crop|Image=Mutation inherited, de novo, somatic.png|Description=Somatic mutations that occur earlier in embryonic development are generally present in a larger fraction of body cells. In F), the mutation happened earlier in development than in G), and therefore is present in more of the child's cells.|bSize=400|cWidth=400|cHeight=150|oTop=352}}The term somatic generally refers to the cells of the body, in contrast to the reproductive ([[germline]]) cells, which give rise to the [[Egg cell|egg]] or [[sperm]]. For example, in [[mammal]]s, somatic cells make up the internal organs, skin, bones, blood, and connective tissue.<ref>{{Cite book|last=Campbell, Neil A., 1946-2004.|title=Biology|date=2009|publisher=Pearson Benjamin Cummings|others=Reece, Jane B.|isbn=978-0-8053-6844-4|edition=8th|location=San Francisco|oclc=174138981}}</ref>

In most animals, separation of germ cells from somatic cells ([[germline development]]) occurs during early stages of [[Embryonic development|development]]. Once this segregation has occurred in the embryo, any mutation outside of the germline cells can not be passed down to an organism's offspring.

However, somatic mutations are passed down to all the progeny of a mutated cell within the same organism. A major section of an organism therefore might carry the same mutation, especially if that mutation occurs at earlier stages of development.<ref name=":0">{{Cite journal|last1=Milholland|first1=Brandon|last2=Dong|first2=Xiao|last3=Zhang|first3=Lei|last4=Hao|first4=Xiaoxiao|last5=Suh|first5=Yousin|last6=Vijg|first6=Jan|date=2017-05-09|title=Differences between germline and somatic mutation rates in humans and mice|journal=Nature Communications|volume=8|article-number=15183|bibcode=2017NatCo...815183M|doi=10.1038/ncomms15183|issn=2041-1723|pmc=5436103|pmid=28485371}}</ref> Somatic mutations that occur later in an organism's life can be hard to detect, as they may affect only a single cell—for instance, a post-[[Mitosis|mitotic]] neuron;<ref name=":5" /><ref name=":1" /> improvements in [[single cell sequencing]] are therefore an important tool for the study of somatic mutation.<ref>{{Cite journal|last1=Gawad|first1=Charles|last2=Koh|first2=Winston|last3=Quake|first3=Stephen R.|date=2016|title=Single-cell genome sequencing: current state of the science|url=http://www.nature.com/articles/nrg.2015.16|journal=Nature Reviews Genetics|language=en|volume=17|issue=3|pages=175–188|doi=10.1038/nrg.2015.16|pmid=26806412|s2cid=4800650|issn=1471-0056|url-access=subscription}}</ref> Both the [[nuclear DNA]] and [[mitochondrial DNA]] of a cell can accumulate mutations; somatic mitochondrial mutations have been implicated in development of some neurodegenerative diseases.<ref>{{Cite journal|last1=Schon|first1=Eric A.|last2=DiMauro|first2=Salvatore|last3=Hirano|first3=Michio|date=2012|title=Human mitochondrial DNA: roles of inherited and somatic mutations|journal=Nature Reviews. Genetics|volume=13|issue=12|pages=878–890|doi=10.1038/nrg3275|issn=1471-0056|pmc=3959762|pmid=23154810}}</ref>

=== Exceptions to inheritance ===
[[File:Hydra oligactis.jpg|alt=|thumb|''[[Hydra oligactis]]'' with two buds. Reproduction by [[budding]] is an exception to the rule that somatic mutations can not be inherited.]]
There are many exceptions to the rule that somatic mutations cannot be inherited by offspring. Many organisms (such as plants and [[basal animals]] like [[sponge]]s and [[coral]]s) do not dedicate a separate germline during early development. Instead they make gametes from stem cells in adult somatic tissues.<ref>{{Cite journal|last1=Schoen|first1=Daniel J.|last2=Schultz|first2=Stewart T.|date=2019-11-02|title=Somatic Mutation and Evolution in Plants|journal=Annual Review of Ecology, Evolution, and Systematics|volume=50|issue=1|pages=49–73|doi=10.1146/annurev-ecolsys-110218-024955|s2cid=203882206|issn=1543-592X|doi-access=free}}</ref><ref name=":2">{{Cite journal|last1=Radzvilavicius|first1=Arunas L.|last2=Hadjivasiliou|first2=Zena|last3=Pomiankowski|first3=Andrew|last4=Lane|first4=Nick|date=2016-12-20|title=Selection for Mitochondrial Quality Drives Evolution of the Germline|journal=PLOS Biology|volume=14|issue=12|article-number=e2000410|doi=10.1371/journal.pbio.2000410|issn=1544-9173|pmc=5172535|pmid=27997535 |doi-access=free }}</ref> In flowering plants, for example, germ cells can arise from adult somatic cells in the floral [[meristem]]. Other animals without a designated germ line include [[tunicate]]s and [[flatworm]]s.<ref>{{Cite journal|last1=Seipel|first1=Katja|last2=Yanze|first2=Nathalie|last3=Schmid|first3=Volker|date=2004|title=The germ line and somatic stem cell gene Cniwi in the jellyfish Podocoryne carnea.|url=http://www.intjdevbiol.com/paper.php?doi=15005568|journal=The International Journal of Developmental Biology|language=en|volume=48|issue=1|pages=1–7|doi=10.1387/ijdb.15005568|pmid=15005568|issn=0214-6282|doi-access=free}}</ref>

Somatic mutations can also be passed down to offspring in organisms that can [[Asexual reproduction|reproduce asexually]], without production of gametes. For instance, animals in the [[cnidaria]]n genus ''[[Hydra (genus)|Hydra]]'' can reproduce asexually through the mechanism of [[budding]] (they can also reproduce sexually). In [[Hydra (genus)|hydra]], a new bud develops directly from somatic cells of the parent hydra.<ref>{{Cite journal|last1=Otto|first1=Joann J.|last2=Campbell|first2=Richard D.|date=1977|title=Budding in Hydra attenuata: Bud stages and fate map|journal=Journal of Experimental Zoology|language=en|volume=200|issue=3|pages=417–428|doi=10.1002/jez.1402000311|pmid=874446|issn=0022-104X}}</ref> A mutation present in the tissue that gives rise to the daughter organism would be passed down to that offspring.

Many plants naturally reproduce through [[vegetative reproduction]]—growth of a new plant from a fragment of the parent plant, without the step of seed production. This can propagate somatic mutations. Humans artificially induce vegetative reproduction via [[grafting]] and stem cuttings.

== Causes ==
[[File:DNA UV mutation.svg|alt=Diagram of UV light causing a pyrimidine dimer|thumb|296x296px|[[Ultraviolet|UV light]] can damage DNA by causing [[pyrimidine dimer]]s. Adjacent bases bond with each other, instead of across the "ladder". The distorted DNA molecule does not function properly. Mutation can result if mistakes occur in [[DNA repair]] or replication.]]
{{See also|Mutagenesis}}
As with germline mutations, mutations in somatic cells may arise due to endogenous factors, including errors during [[DNA replication]] and repair, and exposure to [[reactive oxygen species]] produced by normal cellular processes. Mutations can also be induced by contact with [[mutagen]]s, which can increase the rate of mutation.

Most mutagens act by causing DNA damage—alterations in DNA structure such as [[pyrimidine dimer]]s, or breakage of one or both DNA strands. [[DNA repair]] processes can remove DNA damages that would, otherwise, upon DNA replication, cause mutation. Mutation results from damage when mistakes in the mechanism of [[DNA repair]] cause changes in the nucleotide sequence, or if replication occurs before repair is complete.

Mutagens can be physical, such as radiation from [[Ultraviolet light|UV rays]] and [[X-ray]]s, or chemical—molecules that interact directly with DNA—such as [[(+)-Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide|metabolites]] of [[Benzo(a)pyrene|benzo[''a'']pyrene]], a potent [[carcinogen]] found in [[tobacco smoke]].<ref>{{Cite journal|last1=Armstrong|first1=Ben|last2=Hutchinson|first2=Emma|last3=Unwin|first3=John|last4=Fletcher|first4=Tony|date=2004|title=Lung Cancer Risk after Exposure to Polycyclic Aromatic Hydrocarbons: A Review and Meta-Analysis|journal=Environmental Health Perspectives|language=en|volume=112|issue=9|pages=970–978|doi=10.1289/ehp.6895|issn=0091-6765|pmc=1247189|pmid=15198916}}</ref> Mutagens associated with cancers are often studied to learn about cancer and its prevention.

== Mutation frequency ==

Research suggests that the [[Mutation frequency|frequency of mutations]] is generally higher in somatic cells than in cells of the germline;<ref name=":3">{{Cite journal|last1=Murphey|first1=Patricia|last2=McLean|first2=Derek J.|last3=McMahan|first3=C. Alex|last4=Walter|first4=Christi A.|last5=McCarrey|first5=John R.|date=2013|title=Enhanced Genetic Integrity in Mouse Germ Cells|journal=Biology of Reproduction|volume=88|issue=1|page=6|doi=10.1095/biolreprod.112.103481|issn=0006-3363|pmc=4434944|pmid=23153565}}</ref> furthermore, there are differences in the types of mutation seen in the germ and in the soma.<ref name=":4">{{Cite journal|last1=Chen|first1=Chen|last2=Qi|first2=Hongjian|last3=Shen|first3=Yufeng|last4=Pickrell|first4=Joseph|last5=Przeworski|first5=Molly|date=2017|title=Contrasting Determinants of Mutation Rates in Germline and Soma|journal=Genetics|language=en|volume=207|issue=1|pages=255–267|doi=10.1534/genetics.117.1114|pmid=28733365|pmc=5586376|issn=0016-6731}}</ref> There is variation in mutation frequency between different somatic tissues within the same organism<ref name=":4" /> and between species.<ref name=":0" />

Milholland et al. (2017) examined the mutation rate of [[dermal fibroblast]]s (a type of somatic cell) and germline cells in humans and in mice. They measured the rate of [[single nucleotide variants]] (SNVs), most of which are a consequence of replication error. Both in terms of mutational load (total mutations present in a cell) and mutation rate per [[cell division]] (new mutations with each [[mitosis]]), somatic mutation rates were more than ten times that of the germline, in humans and in mice.

In humans, mutation load in fibroblasts was over twenty times greater than germline (2.8 × 10−7 compared with 1.2 × 10−8 mutations per base pair). Adjusted for differences in the estimated number of cell divisions, the fibroblast mutation rate was about 80 times greater than the germ (respectively, 2.66 × 10−9 vs. 3.3 × 10−11 mutations per base pair per mitosis).<ref name=":0" />

The disparity in mutation rate between the germline and somatic tissues likely reflects the greater importance of genetic integrity in the germline than in the soma.<ref name=":3" /> Variation in mutation frequency may be due to differences in rates of DNA damage or to differences in the DNA repair process as a result of elevated levels of DNA repair enzymes.<ref name=":4" />

In April 2022 it has been reported that most mammals have about the same number of mutations by the time they reach the end of their lifespan, so those that have similar lifespan will have similar somatic [[mutation rate]]s and those who live less/more will have a higher/lower rate of somatic mutations respectively.<ref>{{Cite journal |last1=Cagan |first1=Alex |last2=Baez-Ortega |first2=Adrian |last3=Brzozowska |first3=Natalia |last4=Abascal |first4=Federico |last5=Coorens |first5=Tim H. H. |last6=Sanders |first6=Mathijs A. |last7=Lawson |first7=Andrew R. J. |last8=Harvey |first8=Luke M. R. |last9=Bhosle |first9=Shriram |last10=Jones |first10=David |last11=Alcantara |first11=Raul E. |date=2022-04-21 |title=Somatic mutation rates scale with lifespan across mammals |journal=Nature |language=en |volume=604 |issue=7906 |pages=517–524 |doi=10.1038/s41586-022-04618-z |pmid=35418684 |pmc=9021023 |bibcode=2022Natur.604..517C |issn=0028-0836}}</ref><ref>{{Cite news |date=2022-04-13 |title=Mutations across species reveal clues to ageing |language=en-GB |work=BBC News |url=https://www.bbc.com/news/health-61045950 |access-date=2022-04-20}}</ref>

===Neurons===
Post-mitotic [[neuron]]s accumulate somatic mutations at a constant rate throughout life, and this rate is roughly similar to the mutation rates of [[mitosis|mitotically]] active tissues.<ref name="Abascal2021">Abascal F, Harvey LMR, Mitchell E, Lawson ARJ, Lensing SV, Ellis P, Russell AJC, Alcantara RE, Baez-Ortega A, Wang Y, Kwa EJ, Lee-Six H, Cagan A, Coorens THH, Chapman MS, Olafsson S, Leonard S, Jones D, Machado HE, Davies M, Øbro NF, Mahubani KT, Allinson K, Gerstung M, Saeb-Parsy K, Kent DG, Laurenti E, Stratton MR, Rahbari R, Campbell PJ, Osborne RJ, Martincorena I. Somatic mutation landscapes at single-molecule resolution. Nature. 2021 May;593(7859):405-410. doi: 10.1038/s41586-021-03477-4. Epub 2021 Apr 28. PMID 33911282</ref> The mutations in neurons may arise as a consequence of [[DNA damage (naturally occurring)|endogenous DNA damage]] and the somewhat inaccurate [[DNA repair|repair]] of such damage that occurs all the time in cells.<ref name = Abascal2021/>

=== Somatic hypermutation ===
{{Main|Somatic hypermutation}}
As a part of the [[Adaptive immune system|adaptive immune response]], antibody-producing [[B cell]]s experience a mutation rate many times higher than the normal rate of mutation. The mutation rate in antigen-binding coding sequences of the immunoglobulin genes is up to 1,000,000 times higher than in cell lines outside the lymphoid system. A major step in [[affinity maturation]], somatic hypermutation helps B cells produce antibodies with greater [[antigen]] affinity.<ref>{{Cite journal|last1=Teng|first1=Grace|last2=Papavasiliou|first2=F. Nina|date=2007|title=Immunoglobulin Somatic Hypermutation|journal=Annual Review of Genetics|language=en|volume=41|issue=1|pages=107–120|doi=10.1146/annurev.genet.41.110306.130340|pmid=17576170|issn=0066-4197}}</ref>

== Disease ==
Somatic mutations accumulate within an organism's cells as it ages and with each round of cell division; the role of somatic mutations in the development of cancer is well established, and the accumulation of somatic mutations is implicated in the biology of aging.<ref name=":1">{{Cite journal|last1=Zhang|first1=Lei|last2=Vijg|first2=Jan|date=2018-11-23|title=Somatic Mutagenesis in Mammals and Its Implications for Human Disease and Aging|journal=Annual Review of Genetics|volume=52|pages=397–419|doi=10.1146/annurev-genet-120417-031501|issn=0066-4197|pmc=6414224|pmid=30212236}}</ref>

Mutations in neuronal [[stem cell]]s (especially during [[neurogenesis]])<ref>{{Cite journal|last1=Bae|first1=Taejeong|last2=Tomasini|first2=Livia|last3=Mariani|first3=Jessica|last4=Zhou|first4=Bo|last5=Roychowdhury|first5=Tanmoy|last6=Franjic|first6=Daniel|last7=Pletikos|first7=Mihovil|last8=Pattni|first8=Reenal|last9=Chen|first9=Bo-Juen|last10=Venturini|first10=Elisa|last11=Riley-Gillis|first11=Bridget|date=2018-02-02|title=Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis|journal=Science|language=en|volume=359|issue=6375|pages=550–555|doi=10.1126/science.aan8690|issn=0036-8075|pmc=6311130|pmid=29217587|bibcode=2018Sci...359..550B}}</ref> and in post-mitotic [[neuron]]s lead to genomic heterogeneity of neurons—referred to as "somatic brain mosaicism".<ref name=":5">{{Cite journal|last1=Verheijen|first1=Bert M.|last2=Vermulst|first2=Marc|last3=van Leeuwen|first3=Fred W.|date=2018|title=Somatic mutations in neurons during aging and neurodegeneration|journal=Acta Neuropathologica|language=en|volume=135|issue=6|pages=811–826|doi=10.1007/s00401-018-1850-y|issn=0001-6322|pmc=5954077|pmid=29705908}}</ref> The accumulation of age-related mutations in neurons may be linked to [[Neurodegeneration|neurodegenerative diseases]], including [[Alzheimer's disease]], but the association is unproven. The majority of central-nervous system cells in the adult are post-mitotic, and adult mutations might affect only a single neuron. Unlike in cancer, where mutations result in clonal proliferation, detrimental somatic mutations might contribute to neurodegenerative disease by cell death.<ref>{{Cite journal|last1=Leija-Salazar|first1=M.|last2=Piette|first2=C.|last3=Proukakis|first3=C.|date=2018|title=Review: Somatic mutations in neurodegeneration|journal=Neuropathology and Applied Neurobiology|language=en|volume=44|issue=3|pages=267–285|doi=10.1111/nan.12465|pmid=29369391|s2cid=4362512|url=https://discovery.ucl.ac.uk/id/eprint/10042504/1/Leija-Salazar_et_al-2018-Neuropathology_and_Applied_Neurobiology.pdf}}</ref> Accurate assessment of somatic mutation burden in neurons therefore remains difficult to assess.

=== Role in carcinogenesis ===
{{Further|Somatic evolution in cancer}}
If a mutation occurs in a cell of an organism, that mutation will be present in all the descendants of this cell within the same organism. The accumulation of certain mutations over generations of somatic cells is part of the process of [[malignant transformation]], from normal cell to cancer cell.

Cells with heterozygous loss-of-function mutations (one good copy of a gene and one mutated copy) may function normally with the unmutated copy until the good copy has been spontaneously somatically mutated. This kind of mutation happens often in living organisms, but it is difficult to measure the rate. Measuring this rate is important in predicting the rate at which people may develop cancer.

== See also ==

* [[Mosaic (genetics)]]
* [[Human somatic variation]]

== References ==

{{Reflist}}

[[Category:DNA]]
[[Category:Genetics]]
[[Category:Mutation]]

Somatic mutation - История изменений

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ru>Monkbot: Monkbot/task 21: Replace page(s) with article-number;