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In the broad sense, a mutation can be any heritable change in an organism's morphology, biochemistry, or behavior. The extent to which this can be attributed to DNA mutations depends on the extent to which DNA is ultimately responsible for an organism's heredity. Ever since Watson and Crick, and with the addition of the central dogma of molecular biology, the predominant view is that DNA, and only DNA, is responsible for heredity. However, there are some epigenetic mechanisms of heredity, in which changes to cell membrane content or chromatin structure can be passed on to offspring. At present, the known examples of these are rare, and their status continues to be controversial, but they are perfectly compatible with "mutation" in the broad sense, which is what Neo-Darwinian theory relies on.
Typically though, when we speak of mutation, we're talking about an inherited change to a base pair of DNA. This can be a substitution, in which one nucleotide becomes substituted for another, or it can be an insertion or deletion, in which a nucleotide is either added or removed. In addtion to these small scale changes, there are numerous larger scale types of mutations, in which large tracts of DNA can be duplicated, retrotransposed from RNA, inverted, rearranged, or experience any number of other changes. Whole genomes can even be duplicated, creating an extra set of genes, as is the case with polyploid plants. This can create some confusion, because creationist and IDist critics often limit their discussion to point mutations (see "Types of Mutation" below), and rarely if ever consider larger scale changes which are extremely important in evolution.
DNA consists of four different nucleotides: adenine, thymine, cytosine, and guanine; (abbriviated A, T, C, and G, respectively). Due to their structure, A and G are known as purines, while C and T are called pyrimidines. Individual genes typically consist of many thousands of these nucleotides. DNA exists as a double strand, where each nucleotide binds to a complementary nucleotide on the opposite strand, forming what is called a "base pair". A always binds to T, and C always binds to G. Because of this, if you know the sequence of one strand, you can always figure out the sequence of the complementary strand.
Due to the chemical nature of these nucleotides, they can often change due to spontaneous mutation (in the absence of any known cause), or changes can be induced by mutagens (substances or radiation that increase the rate of mutation). Most of these changes are repaired by enzymes in the cell, but some changes can escape this repair or even be caused by it, and so will be transitted to the next generation of that cell. Once the change is in the next generation, it can no longer be repaired, and hence is now known as a mutation (before this point, it isn't necessarily heritable, and so isn't classified as a mutation).
In multi-cellular organisms, not all cells will lead to a new organism. Therefore, only mutations that occur in gametes will be passed on to the next generation, so are termed "germ-line mutations". All other mutations are known as "somatic mutations".
Mutation is the ultimate source of variation on which natural selection acts. Heritable variation is a necessary requirement for Charles Darwin's theory of evolution; in the absence of new variation, natural selection can only make populations more uniform, and this would be unable to bring about long-term adaptive change. One of Darwin's greatest concerns was that he had no knowledge of where heritable variation came from. Unfortunately, he was unware of the work of Gregor Mendel, whose pioneering work on genetics was begining to uncover the nature of heritability.
While Mendel's work was largely ignored during his lifetime, it began to be rediscovered in the early 20th century. Walter Sutton, Theodor Boveri, and Anton von Tschermak each independently rediscovered Mendel's work, and realized that the behavior of chromosomes -- easilly stained structures within the nucleus of a cell, which segregate upon reproduction -- could explain how Mendel's laws worked. This led to the chromosomal theory of inheritance. Meanwhile, researchers such as Thomas H. Morgan and William Bateson, using the fruitfly Drosophila melanogaster, found that Mendel's laws were essentially correct. One important outcome was the discovery that inheritance is particulate -- meaning that it existed as discrete units -- rather than blending, as had been previously believed. This led Bateson to coin the term "genetics" in 1909 to describe the science which studied these particles of heredity, which he called "genes". The actual make-up of genes was at that time still unknown, despite the growing popularity of the chromosomal theory.
The Neo-Darwinian synthesis of the 1930s incorporated the notion that genes were the units of heredity into Darwin's theory of natural selection. This held that mutations in the gene were what was selected for by natural selection, which allowed for new variation to be constantly added to a population. However, it was still not known what caused a mutation, because it was not known just what it was that was mutating. While the chromosomal theory of inheritance was widely accepted, it was not known how the chromosomes carried genetic information.
Chromosomes are made up of two types of macromolecules: protein and nucleic acid. It was originally believed that proteins would be the genetic material. Proteins are far more diverse, being made of 20 different subunits, and they have an enormous variety of chemical attributes. Nucleic acids, on the other hand, use only 4 subunits and were regarded as comparatively boring. However, two key experiments, the first by Avery, McLeod and McCarty in 1944, and the second by Hershey and Chase in 1952, gave strong evidence that nucleic acid and not protein was the genetic material. But the discovery of the double helical structure of DNA in 1953, by James Watson and Francis Crick, finally established nucleic acid as the winner. With the structure of DNA in hand, it was now apparent how genetic information was stored, and how a mutation in one of the base pairs of DNA could change that information.
Types of Mutations
The types of mutations are summarized briefly:
- Point Mutations: Point mutations are changes to single DNA nucleotides, as opposed to changes involving many nucleotides at once. The three kinds of point mutations are substitutions, deletions, or insertions.
- Substitution: A substitution is when a base pair is exchanged for a different base pair. For example:
- 5'-AATGCGGT-3' -> 5'-AATGGGGT-3'
- Transitions: A transition is a substitution in which the purine/pyrimidine orientation on a given strand remains the same. That is, changing from pyrimidine to pyrimidine (eg C--> T) or purine to purine (eg A--> G).
- Transversion: The opposite of transition, a transversion is a substitution in which the purine/pyrimidine orientation on a given strand is changed. That is, changing from purine to pyrimidine (eg A--> T) or pyrimidine to purine (eg C--> A). Transversions are less common than transitions, because they require a greater change in chemical structure of the nucleotides.
- Insertion: One or more nucleotides are inserted into the DNA sequence. For example:
- 5'-AATGCGGTA-3' -> 5'-AATGCAGGTA-3'
- Deletion: One or more nucleotides are deleted from the DNA sequence. For example:
- 5'-AATGCGGTA-3' -> 5'-AATGGGTA-3'
- Larger mutations: These mutations involve many nucleotides at once. This can include the deletion or insertion of a sequence. Some specific types of interest are listed below.
- Inversion: An inversion is when a small sequence of DNA is picked up and effectively turned around. The portion that is inverted will now read backwards. For example:
- 5'-AATGCGGTA-3' -> 5'-AAGCGTGTA-3'
- Rearrangement: A rearrangement is when DNA sequences become "shuffled" such that their juxtaposition becomes changed. For example, if two sections of a gene become switched with each other:
- 5'-AATGCGGTA-3' -> 5'-GGTGCAATA-3'
- Gene/Exon Duplications: This is where a whole gene or a coding part of a gene (an exon) is duplicated. Depending on the mechanism of duplication, the newly created gene may end up close to the old one, or far away. These are very important from an evolutionary standpoint. As a very small-scale example:
- 5'-ATGCCGTGAAATGCGGTA-3' -> 5'-ATGCCGTGAAATGCGGTAATGCCGTGA-3'
- Transposition: A special kind of duplication in which a segment of DNA, known as a transposable element, is able to duplicate itself and insert itself elsewhere in the genome. These have many qualities in common with viruses, and are in fact often related to or derived from them.
- Retrotransposition: Similar to transposition, retrotransposons are first transcribed into RNA, and then RNA is then reverse transcribed into DNA by an enzyme known as reverse transcriptase. This is then inserted at some point in the genome. They are similar to retroviruses.
- Chromosomal mutations: These are very large scale mutations. They involve whole chromosomes or pieces of them, and can alter or duplicated hundreds or thousands of genes at a time. They are an imporant source for new genetic material.
- Translocation: Part of a chromosomal arm is removed from that chromosome and attached to another.
- Fusion: Two chromosomes get fused together, resulting in a single chromosome. There is evidence of such a fusion in the human genome, resulting in one fewer chromosome pairs than is found in great apes.
- Fission: The opposite of fusion. One chromosome becomes two.
- Segmental Duplication: This is the duplication of a large segment of a chromosome.
- Chromosomal Duplication: The duplication of an entire chromosome.
- Genome Duplication: This is where the entire genome gets duplicated, forming two or more copies, also known as polyploidy. For example, the organism goes from being diploid (2n) to tetraploid (4n). There is evidence that all vertebrates have descend from an ancestor that underwent either one or two rounds of whole genome duplication.
Effects of Mutations
Mutations can have a wide variety of effects depending on the function of the DNA in which they occur. The most well-known function of DNA is that of protein coding. Protein coding DNA is transcribed into RNA, which is then translated into proteins. Proteins have physiological functions which help to specify the organism's phenotype; they are the workhorse of life as we know it. This is a major way in which DNA is responsible for heritable variation. Within a coding sequence, every three nucleotides constitute what is known as a codon, and each codon codes for a particular amino acid according to the genetic code. The genetic code is what is known as 'redundant' or 'degenerate': there are more codons than there are amino acids; therefore, each amino acid can be coded for by more than one codon, but a given codon can never code for more than one amino acid (with some rare exceptions). It is therefore possible to know the amino acid sequence of a protein based only on the DNA sequence of a gene, but only part of the DNA sequence can be determined from the corresponding amino acid sequence.
As it turns out, only a small percentage (around 3% in H. sapiens) of eukaryotic DNA is protein coding. The function of the rest is not clear -- some of it is regulatory, structural, or carries out other functions; but most of it is probably what is known as junk DNA or selfish DNA. Listed below are some common terms for mutational effects in protein coding DNA.
- Silent Mutation: A silent mutation is one that has no effect on the amino acid sequence of the protein. Since the genetic code is redundant, and most amino acids can be coded for by more than one codon, a substitution may change codons without changing amino acids. For example, the amino acid proline is coded for by the codons CC-, where - is any nucleotide. Therefore, any mutation at that position will be silent. In general, it's the third base of the codon, often called the "wobble base", that can be mutated without changing the amino acid that it codes for.
- Frameshift: A frameshift is a dramatic change to an amino acid sequence that results from changing the frame in which the codons are read. These usually occur as a result of a single insertion or deletion (in/del); any larger in/del that is not divisible by three can also cause a frameshift. A frameshift will change all of the codons that are downstream of where the insertion or deletion occurs. This may be of little consequence if it's near the end of a gene, or of great consequence if it's near the beginning.
- To understand how a frameshift works, and why its effects can be dramatic, consider an analagous example in English:
- THE DOG ATE THE CAT WHO ATE THE RAT
- Now let's insert an "R" after the first G:
- THE DOG RAT ETH ECA TWH OAT ETH ERA T
- You can see how everything after the insertion has now been changed, and why frameshifts are sometimes called gibberish mutations.
- Missense Mutation: This is when one codon is replaced with another that codes for a different amino acid. The result is a protein with one amino acid that's been substituted for another. There are relatively common, and since proteins tend to have a lot of plasticity (most of the protein doesn't have a significant function), they readily tolerate missense mutations. Missense mutations may be divided into two types:
- Non-conservative Mutation: This is when the substituted amino acid is quite different in its chemical properties to the original. For example, a mutation to a codon for Leucine from a codon for Lysine is non-conservative, as one amino acids is non-polar with branched side-chains but the other is linear and positively charged at neutral pH.
- Nonsense Mutation: This is when a point mutation changes an amino acid codon into a "Stop" codon. The causes the amino acid chain to stop growing prematurely, and the result is a truncated protein.
- Suppressor Mutation: This is when a mutation counteracts the phenotypic effect of a previous mutation. For example, say a mutation causes the codon 'AGA' (which codes for the amino acid Arginine) to change to 'AGC' (which codes for the amino acid Serine, a very different amino acid to Arginine). A suppressor mutation may be one that changes the mutated codon to 'CGC' (which also codes for Arginine), or to 'AAG' (which codes for Lysine, a similar amino acid to Arginine).
- Spontaneous mutation
- Mutation rates
- Junk DNA
- Evolution of new information
- Material for Natural Selection
- Gene expression
- Evolution of new information
This page is part of the EvoWiki encyclopedia of genetics and molecular biology.