Mutation
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[edit] Introduction
A mutation is a change to the DNA of a cell, including small local changes to genetic information, or restructuring of the chromosomes, or changes in chromosome number. Readers uncertain of what DNA is, or what a chromosome is, should consult those articles before attempting to read further.
This article explains the biological basis of mutations and the effect they have on cell function. For a discussion of the role of such mutations in the theory of evolution, and a discussion of the common misconceptions on this point, consult our article on Mutation and Evolution.
[edit] Point Mutations
Point mutations are small localized changes to the DNA. They can be caused by errors in DNA replication, or by damage caused by chemical mutagens or radiation. To explain the significance of such changes, let us recapitulate the relationship between DNA and proteins.
Bearing this in mind, we can look at the various kinds of point mutations and their potential effects on the proteins that the altered DNA codes for.
A substitution involves the change of a base in the DNA. So, for example, the miniature gene that we're using as an example might get miscopied as ATG GCC ACG TTC TGA AAA.
Such a substitution will usually change at most one amino acid: in this case, the new sequence of amino acids will be Met-Ala-Thr-Phe. There are also "silent mutations" that don't change the amino acid at all, because of the redundancy in the genetic code. In particular, a mutation to the third base of a codon often has little effect, as you can see from the table of the genetic code.
A substitution can potentially have more sweeping effects. Recall that the sequence ATG, besides coding for methionine, also functions as a start codon: no translation will take place until the first instance of ATG in the gene. In the case of our little example gene, a mutation to the ATG codon would mean that nothing got translated at all; in a real gene, which would be longer, there would most likely be another ATG somewhere in the gene, and translation would start from there. The effect would be to delete the start of the chain of amino acids.
Similarly, a mutation which turns a stop codon into a codon coding for some amino acid will cause the process of translation to run on beyond the point where it should have stopped.
We should note that some people use the term "point mutation" to refer exclusively to substitutions, a practice that we have not followed.
An insertion, as the name suggests, involves the insertion of one or more bases into the DNA. If the number of bases inserted is not exactly divisible by three, then this will cause a frame shift: the bases following the insertion will group into codons differently.
For example, suppose our toy gene undergoes the insertion of an G just after the fourth base, so that now it reads ATG CGC CAC GTT CTG AAA A. Every codon following, and including, the affected codon is now different, and so are all the amino acids: the chain is now Met-Arg-His-Val-Leu-Lys. (Note the disruption of the stop codon.)
Obviously this brings about a radical change in the structure of the protein which is usually disastrous; however, such a frame shift is sometimes beneficial: see the examples of vancomycin-dependent enterococci and of bacteria that produce nylonase in our article on beneficial mutations.
An insertion of a number of bases exactly divisible by three will result in the insertion of amino acids into the chain, and possibly a change to the adjacent amino acids. For example, ATG CCC TAT ACG TTC TGA AAA will be translated as Met-Pro-Tyr-Thr-Phe, whereas if the insertion cuts across a codon boundary, as, for example, ATG CTA TCC ACG TTC TGA AAA, then we get Met-Leu-Ser-Thr-Phe.
Deletion is the opposite of insertion, and the same remarks apply: the deletion of a number of bases not divisible by three will cause a frame shift.
In this discussion of the role of point mutations, we have concentrated on those that affect protein-coding portions of the DNA. A point mutation can also affect a bit of DNA that does nothing in particular; or it can affect a part that doesn't code for amino acids but does affect cell function. For example, a change to the promoter region that controls gene transcription may result in the affected gene being transcribed more, or less, or not at all.
[edit] Changes to chromosome structure
Deletion is just what it sounds like: a chunk of chromosome goes missing.
The loss of any substantial piece of a chromosome will usually prevent a zygote from developing, or at the very least from developing properly.
You might suppose that an inversion would result in the genes on the inverted section being read back-to-front, making a nonsense of them. However, remember that every bit of DNA has a built-in direction --- it has a 5' end and a 3' end. In transcription, the coding strand is transcribed in the 5' → 3' direction, and the fact that the inverted part has been turned around in the DNA doesn't affect which is the 5' end and which the 3' end of each strand of the inverted part.
Fusion is caused by a translocation in which both chromosomes break into a big bit and a small bit, and the two big bits get stuck together into one large chromosome, and the two small bits get stuck together into a little nubbin of a chromosome, which then gets lost during cell division. (This is especially likely if the smaller piece has no centromere, as then it can't take part properly in mitosis and meiosis.) The result is the fusion of the chromosomes into one big chromosome, minus the small amount of material that's been lost, and so this process results in a change of chromosome number.
Fission involves a chromosome splitting at the centromere, and not being repaired, in such a way that the two resulting chromosomes each have enough of a centromere to be getting on with, and can take part in mitosis and meiosis.
Duplications are of particular interest in the study of evolution. Once a duplication has taken place, further point mutations to either one of the duplicates will not, of course, affect the other, and so over time you would get two similar, but not identical genes, coding for similar but not identical polypeptides. Repetition of the process of duplication and diversification would produce a whole "family" of genes with diverse functions. There are a number of well-studied gene families, such as the Hox genes[1], the beta-like globin genes[2], and the opsin gene family[3], which have every appearance of such an evolutionary history.
[edit] Changes in chromosome number
Besides the processes of fission and fusion described above, changes in chromosome number can be caused by mistakes in the process of meiosis. If sister chromosomes don't separate properly during anaphase I, or sister chromatids don't separate properly during anaphase II, or both, then the result will be that the chromosomes are shared out unequally among the four gametes produced by the meiosis of the cell, so that on fertilization, the resulting zygote will have more or fewer copies of some chromosome, or of all its chromosomes, than its parents did.
In animals, such changes in chromosome number are almost invariably bad, causing spontaneous abortion, early death, various handicaps, or sterility. Plants, on the other hand, are quite tolerant of events which add whole sets of chromosomes; such changes can (and, observably, do[4]) result in reproductive isolation and the formation of new plant species literally within a generation. This process can recur several times through the history of a plant lineage. Strawberries, for example are octoploid --- they have eight homologues of each chromosome, and this cannot be the result of a single error in meiosis.
[edit] Note on somatic and germ-line mutations
Mutations may also be classed as germ-line or somatic. A germ-line mutation is one which affects a gamete. Such mutations are heritable, and are the mutations that chiefly interest geneticists, and the only mutations important to the theory of evolution.
A somatic mutation is one that affects an ordinary cell. Such mutations are not heritable, and are usually not noticeable, unless they are one of the sort that causes unrestrained cell division (i.e. cancer).
In organisms which are single-celled and reproduce asexually by cell division, there is no distinction between the two: any mutation will be inherited.
[edit] Misconceptions
There are a number of misconceptions about mutation, promulgated by creationists, or comic books, or indeed by creationist comic books.
The first is to misunderstand the role of mutation in the theory of evolution: for this, see our article on Mutation and Evolution.
The second is to claim that there are no beneficial mutations: for a collection of counterexamples, see our article on Beneficial Mutations.
A third is to claim that mutations "cannot increase information": for three good reasons why this is nonsense, consult our article on Mutations and Information.
