The word somatic comes from the Greek word soma which means "body", and somatic mutations only affect the present organism's body. From an evolutionary perspective, somatic mutations are uninteresting, unless they occur systematically and change some fundamental property of an individual--such as the capacity for survival.
For example, cancer is a potent somatic mutation that will affect a single organism's survival. As a different focus, evolutionary theory is mostly interested in DNA changes in the cells that produce the next generation. The statement that mutations are random is both profoundly true and profoundly untrue at the same time.
The true aspect of this statement stems from the fact that, to the best of our knowledge, the consequences of a mutation have no influence whatsoever on the probability that this mutation will or will not occur. In other words, mutations occur randomly with respect to whether their effects are useful.
Thus, beneficial DNA changes do not happen more often simply because an organism could benefit from them. Moreover, even if an organism has acquired a beneficial mutation during its lifetime, the corresponding information will not flow back into the DNA in the organism's germline.
However, the idea that mutations are random can be regarded as untrue if one considers the fact that not all types of mutations occur with equal probability. Rather, some occur more frequently than others because they are favored by low-level biochemical reactions. These reactions are also the main reason why mutations are an inescapable property of any system that is capable of reproduction in the real world.
Mutation rates are usually very low, and biological systems go to extraordinary lengths to keep them as low as possible, mostly because many mutational effects are harmful. Nonetheless, mutation rates never reach zero, even despite both low-level protective mechanisms, like DNA repair or proofreading during DNA replication , and high-level mechanisms, like melanin deposition in skin cells to reduce radiation damage. Beyond a certain point, avoiding mutation simply becomes too costly to cells.
Thus, mutation will always be present as a powerful force in evolution. So, how do mutations occur? The answer to this question is closely linked to the molecular details of how both DNA and the entire genome are organized. The smallest mutations are point mutations, in which only a single base pair is changed into another base pair.
Yet another type of mutation is the nonsynonymous mutation, in which an amino acid sequence is changed. Such mutations lead to either the production of a different protein or the premature termination of a protein.
As opposed to nonsynonymous mutations, synonymous mutations do not change an amino acid sequence, although they occur, by definition, only in sequences that code for amino acids. Synonymous mutations exist because many amino acids are encoded by multiple codons. Base pairs can also have diverse regulating properties if they are located in introns , intergenic regions, or even within the coding sequence of genes.
For some historic reasons, all of these groups are often subsumed with synonymous mutations under the label "silent" mutations. Depending on their function, such silent mutations can be anything from truly silent to extraordinarily important, the latter implying that working sequences are kept constant by purifying selection.
This is the most likely explanation for the existence of ultraconserved noncoding elements that have survived for more than million years without substantial change, as found by comparing the genomes of several vertebrates Sandelin et al.
Mutations may also take the form of insertions or deletions, which are together known as indels. Indels can have a wide variety of lengths. At the short end of the spectrum, indels of one or two base pairs within coding sequences have the greatest effect, because they will inevitably cause a frameshift only the addition of one or more three-base-pair codons will keep a protein approximately intact.
At the intermediate level, indels can affect parts of a gene or whole groups of genes. At the largest level, whole chromosomes or even whole copies of the genome can be affected by insertions or deletions, although such mutations are usually no longer subsumed under the label indel. At this high level, it is also possible to invert or translocate entire sections of a chromosome, and chromosomes can even fuse or break apart. If a large number of genes are lost as a result of one of these processes, then the consequences are usually very harmful.
Of course, different genetic systems react differently to such events. Finally, still other sources of mutations are the many different types of transposable elements, which are small entities of DNA that possess a mechanism that permits them to move around within the genome.
Some of these elements copy and paste themselves into new locations, while others use a cut-and-paste method. Such movements can disrupt existing gene functions by insertion in the middle of another gene , activate dormant gene functions by perfect excision from a gene that was switched off by an earlier insertion , or occasionally lead to the production of new genes by pasting material from different genes together.
Figure 1: The overwhelming majority of mutations have very small effects. This example of a possible distribution of deleterious mutational effects was obtained from DNA sequence polymorphism data from natural populations of two Drosophila species. The spike at includes all smaller effects, whereas effects are not shown if they induce a structural damage that is equivalent to selection coefficients that are 'super-lethal' see Loewe and Charlesworth for more details.
A single mutation can have a large effect, but in many cases, evolutionary change is based on the accumulation of many mutations with small effects. Not everyone who is exposed to carcinogens will develop cancer, and the presence of tumor suppressor genes is part of the reason why this is the case. Examples of tumor suppressor genes include BRCA genes and the p53 gene.
It is usually but not always a combination of mutations in oncogenes and tumor suppressor genes that leads to the development of cancer. Genes and chromosomes can be damaged in a number of different ways.
They may be damaged directly, such as with radiation, or indirectly. Substances that can cause these mutations are referred to as carcinogens. While carcinogens may cause mutations that begin the process of cancer formation induction , other substances that aren't carcinogenic themselves may lead to progression promoters.
An example is the role of nicotine in cancer. Nicotine alone does not appear to be an inducer of cancer, but may promote the development of cancer following exposure to other carcinogens. Mutations also occur commonly due to the normal growth and metabolism of the body. Every time a cell divides there is a chance that an error will occur. There are also non-structural changes that appear to be important in cancer. The field of epigenetics looks at changes in the expression of genes that aren't related to structural changes such as DNA methylation, histone modification, and RNA interference.
In this case, the "letters" that make up the code that is interpreted is unchanged, but the gene may be essentially turned on or off. An encouraging point that has risen from these studies is that epigenetic changes in contrast to structural changes in DNA may sometimes be reversible. As the science of cancer genomics advances, it's likely we will learn much more about the particular carcinogens that lead to cancer. Already, the "genetic signature" of a tumor has been found in some cases to suggest a particular risk factor.
For example, certain mutations are more common in people who smoke who develop lung cancer, while other mutations are often seen in never smokers who develop the disease. Somatic gene mutations are those that are acquired after birth or at least after conception as some may occur during the development of the fetus in the uterus.
They are present only in the cells that become a malignant tumor and not all the tissues of the body. Somatic mutations that occur early in development may affect more cells mosaicism. Somatic mutations are often referred to as driver mutations as they drive the growth of a cancer. In recent years, a number of medications have been developed that target these mutations to control the growth of a cancer. When a somatic mutation is detected for which a targeted therapy has been developed, it is referred to as an actionable mutation.
The field of medicine known as precision medicine is a result of medications such as this that are designed for specific gene mutations in cancer cells. You may hear the term "genomic alterations" when talking about these therapies as not all changes are mutations per se.
For example, some genetic changes consist of rearrangements and more. Germline mutations are those that are inherited from a mother or father and are present at the time of conception.
The term "germline" is due to the mutations being present in eggs and sperm which are called "germ cells. Sometimes a mutation occurs at the time of conception sporadic mutations such that it is not inherited from a mother or father but can be passed down to offspring.
Germline mutations may be "dominant" or "recessive". In autosomal dominant diseases, one parent has a normal copy of the gene and a mutated copy; there is a chance a child will inherit the mutation and be at risk for the disease. In autosomal recessive diseases, two copies of the mutated gene are required to cause the disease. Each parent has one normal gene and one mutated gene; only one in four children will inherit the mutated gene from both parents and therefore be at risk of the disease.
So, how do they occur? These mutations may occur when the person is exposed to something in the environment. Cigarette smoke, radiation, hormone use and diet may also lead to acquired mutations that may affect cancer risk. Other acquired mutations may occur randomly as the cells divide, with no identifiable cause. These are seen for the first time in a child—but neither parent.
They may occur if a variant exists in the egg or sperm cell of one of the parents. A de novo variant may also arise in the fertilized egg. De novo variants are one explanation for genetic disorders that occur in a child, but not in his or her parents.
This is known as predictive genetic testing. The decision to undergo this type of testing is personal, and typically based on personal or family history of cancer. Some tests look for a single gene, while others look for harmful variants in multiple genes at the same time panel testing.
Mutations in these genes are not known to be inherited. HER2, a specialized protein that controls cancer growth and spread. It is found in some cancer cells. For example, breast and ovarian cancer cells.
The RAS family of genes, which makes proteins involved in cell communication pathways, cell growth, and cell death. DNA repair genes. These fix mistakes made when DNA is copied. Many of them function as tumor suppressor genes. If a person has an error in a DNA repair gene, mistakes remain uncorrected.
Then, the mistakes become mutations. These mutations may eventually lead to cancer, particularly mutations in tumor suppressor genes or oncogenes. Mutations in DNA repair genes may be inherited or acquired. Lynch syndrome is an example of the inherited kind. Researchers have learned a lot about how cancer genes work.
But many cancers are not linked with a specific gene. Cancer likely involves multiple gene mutations. Moreover, some evidence suggests that genes interact with their environment.
This further complicates our understanding of the role genes play in cancer. Researchers continue to study how genetic changes affect cancer development. This knowledge has led to improvements in cancer care, including early detection, risk reduction, the use of targeted therapy , and survival.
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