Somatic mutation

The term somatic generally refers to the cells of the body, in contrast to the reproductive (germline) cells, which give rise to the egg or sperm. For example, in mammals, somatic cells make up the internal organs, skin, bones, blood, and connective tissue. In most animals, separation of germ cells from somatic cells (germline development) occurs during early stages of 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. 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-mitotic neuron; 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. Exceptions to inheritance '' 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 sponges and corals) do not dedicate a separate germline during early development. Instead they make gametes from stem cells in adult somatic tissues. 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 tunicates and flatworms. Somatic mutations can also be passed down to offspring in organisms that can reproduce asexually, without production of gametes. For instance, animals in the cnidarian genus Hydra can reproduce asexually through the mechanism of budding (they can also reproduce sexually). In hydra, a new bud develops directly from somatic cells of the parent hydra. 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 ==

can damage DNA by causing pyrimidine dimers. 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. 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 mutagens, which can increase the rate of mutation. Most mutagens act by causing DNA damage—alterations in DNA structure such as pyrimidine dimers, 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 UV rays and X-rays, or chemical—molecules that interact directly with DNA—such as metabolites of Benzo(a)pyrene|benzo[a]pyrene, a potent carcinogen found in tobacco smoke. Mutagens associated with cancers are often studied to learn about cancer and its prevention. == Mutation frequency ==

Research suggests that the frequency of mutations is generally higher in somatic cells than in cells of the germline; furthermore, there are differences in the types of mutation seen in the germ and in the soma. There is variation in mutation frequency between different somatic tissues within the same organism Neurons Post-mitotic neurons accumulate somatic mutations at a constant rate throughout life, and this rate is roughly similar to the mutation rates of mitotically active tissues. The mutations in neurons may arise as a consequence of endogenous DNA damage and the somewhat inaccurate repair of such damage that occurs all the time in cells. == 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. Mutations in neuronal stem cells (especially during neurogenesis) and in post-mitotic neurons lead to genomic heterogeneity of neurons—referred to as "somatic brain mosaicism". The accumulation of age-related mutations in neurons may be linked to 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. Accurate assessment of somatic mutation burden in neurons therefore remains difficult to assess. Role in carcinogenesis 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 ==