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When a cell reproduces, its DNA and genes are physically replicated. Normally an exact copy of the parental DNA is produced, but sometimes a copying error happens. The set of enzymes that replicate the DNA include proof-reading and repair enzymes. These enzymes detect and correct most of the copying errors, but some errors persist even after proof-reading and repair. These errors are called mutations. The new sequence of

Protein chain

Transfer RNA

Messenger RNA

Ribosome Chromosome Gene Messenger

RNA

Translation Protein

Figure 2.3

The transfer of information in a cell.

Much of the DNA does not code for genes

DNA that results from a mutation may code for a form of protein with different prop-erties from the original. Mutations can happen in any cell, but the most important mutations, for the theory of evolution, are those occuring in the production of the gametes. These mutations are passed on to the offspring, who may differ from their parents because of the mutation.

Various kinds of mutation can occur. One is point mutation, in which a base in the DNA sequence changes to another base. The effect of a point mutation depends on the kind of base change (Figure 2.4a– c). Synonymous, or silent, mutations (Figure 2.4a) are mutations between two triplets that code for the same amino acid, and have no effect on the protein sequence. Non-synonymous, or meaningful, point mutations do change the amino acid. Because of the structure of the genetic code (Table 2.1), most synonymous mutations are in the third base position of the codon. About 70% of changes in the third position are synonymous, whereas all changes in the second and most (96%) at the first position are meaningful. Another distinction for point muta-tions is between transimuta-tions and transversions. Transimuta-tions are changes from one

Original DNA sequence

Different sorts of mutation. (a) Synonymous mutations a the base changes but the amino acid encoded does not.

(b) Transition a a change between purine types or between pyrimidine types. (c) Transversion a a change from purine to pyrimidine or vice versa. (d) Frameshift mutation a a base is inserted. (e) Stop mutation a an amino acid-encoding triplet mutates to a stop codon. The terms transition and transversion can apply to synonymous or amino acid-changing mutations,

but it has only been illustrated here for mutations that alter amino acids. The base sequence here is for the DNA. The genetic code is conventionally written for the mRNA sequence;

thus G has to be transcribed to C, etc. when comparing the figure with Table 2.1 (the genetic code). (The figure is stereochemically unconventional because the 3′ end has been put at the left and 5′ at the right; but this detail is unimportant here.)

Different kinds of mutation can be distinguished, such as . . .

. . . point mutations . . .

pyrimidine to the other, or from one purine to the other: between C and T, and between A and G. Transversions replace a purine base by a pyrimidine, or vice versa:

from A or G to T or C (and from C or T to A or G). The distinction is interesting because transitional changes are much commoner in evolution than transversions.

Successive amino acids are read from consecutive base triplets. If, therefore, a muta-tion inserts a base pair into the DNA, it can alter the meaning of every base “down-stream” from the mutation (Figure 2.4d). These are called frameshift mutations, and will usually produce a completely nonsensical, functionless protein. Another kind of mutation is for a previously coding triplet to mutate to a “stop” codon (Figure 2.4e);

the resulting protein fragments will probably again be functionless.

Some stretches of non-coding DNA consist of repeats of a short unit sequences.

These sequences are particularly vulnerable to a kind of error called slippage (Fig-ure 2.5). In slippage, the DNA strand that is being copied from slips relative to the new strand that is being created. A short stretch of nucleotides is then missed out or copied twice. Slippage contributes to the origin of non-coding DNA that consists of repeats of short unit sequences. However, slippage can also occur in DNA other than repetitive non-coding DNA. Slippage can cause frameshift mutations (Figure 2.4d), for instance.

The mutational mechanisms we have considered so far concern single nucleotides, or short stretches of nucleotides. Other mutational mechanisms can influence larger chunks of DNA. Transposition is an important example. Transposable elements a informally known as “jumping genes” a can copy themselves from one site in the DNA to another (Figure 2.6a). If a transposable element inserts itself into an existing gene, it will corrupt that gene; if it inserts itself into a region of non-coding DNA, it may do less or even no damage to the body. Transposable elements can pick up a stretch of DNA and copy it as well as itself into the new insertion site. Transposition usually alters the total length of the genome, because it creates a new duplicated stretch of DNA. This contrasts with a simple miscopying of a nucleotide, in which the total length of the genome is unchanged. Unequal crossing-over is another kind of mutation that can duplicate (or, unlike transposition, delete) a long stretch of DNA (Figure 2.6b).

Finally, mutations may influence large chunks of chromosomes, or even whole chromosomes (Figure 2.7). A length of chromosome may be translocated to another

Either Or

Slippage happens when a stretch of DNA is copied twice or not at all. r in the figure is a certain sequence of DNA. It is repeated three times in a region of the DNA molecule. This molecule is being copied, and r′ refers to the same unit sequence in the new DNA molecule. In this case the DNA polymerase has slipped past one repeat and the new molecule has two rather than three repeats.

It is also possible for the polymerase to slip back and copy a unit repeat twice; then the new molecule has four repeats. The old and new copies will have different numbers of repeats. They may be repaired to create a mutant DNA (with two or four repeats) or to restore the original number of three repeats. Sections of DNA with many repeats of a similar sequence may be particularly vulnerable to slippage.

. . . frameshift mutations . . .

. . . slippage . . .

. . . transposition . . .

chromosome, or to another place on the same chromosome, or be inverted. Whole chromosomes may fuse, as has happened in human evolution; chimps and gorillas (our closest living relatives) have 24 pairs of chromosomes whereas we have 23. Some or all of the chromosomes may be duplicated. The phenotypic effects of these chromosomal mutations are more difficult to generalize about. If the break-points of the mutation divide a protein, that protein will be lost in the mutant organism. But if the break is between two proteins, any effect will depend on whether the expression of a gene depends on its position in the genome. In theory, it might not matter whether a protein is transcribed from one chromosome or another; though in practice gene expression is probably at least partly regulated by relations between neighboring genes and a chromosomal mutation will then have phenotypic consequences.

(a) Transposition (by reverse transcription)

Transposition and unequal crossing-over are mutation mechanisms that affect stretches of DNA longer than one or two nucleotides. They duplicate DNA laterally through the genome.

(a) Transposition can occur by more than one mechanism. Here transposition occurs via an RNA intermediate that is copied back into the DNA by reverse transcription. Transposable elements of this kind are called retroelements. (b) Unequal crossing-over happens when the sequences of the two chromosomes are misaligned at recombination (for recombination, see Figure 2.9 below). In the simple case illustrated here, chromosomes with three and with one copy of a gene could be generated from two chromosomes with two genes each. In practice, misalignment is more likely if there are a long series of copies of similar sequences.

Figure 2.7 gains more than the other). In addition, whole chromosomes may fuse, and whole

chromosomes (or the whole genome) may duplicate.

. . . and chromosomal mutations

Mutations can also delete, or duplicate, a whole chromosome. Mutations on the largest scale can duplicate all the chromosomes in the genome. The duplication of the whole genome is called polyploidy. For example, suppose that the members of a normal diploid species have 20 chromosomes (10 from each parent). If all 20 are duplicated in a mutation, the offspring has 40 chromosomes. Polyploidy has been an important process in evolution, particularly plant evolution (Chapters 3, 14, and 19).

That concludes our review of the main types of mutation. It is not a complete list of all known mutation mechanisms, but is enough for an understanding of the evolution-ary events described later in this book.