To create new copies of DNA, an assembly of incredibly complex molecules act as machines that separate the DNA into two strands, splitting it down the middle of each ladder rung as though unzipping a zipper. These molecular machines then reconstruct each half of the DNA into a new DNA molecule by matching each nucleobase with a partner: adenine (A) always pairs with thymine (T), and cytosine (C) always pairs with guanine (G). This results in two perfect copies of the original genetic code—provided everything works as expected.
Occasionally, however, something goes wrong. Sometimes the molecular machinery malfunctions. This doesn’t happen very often, because the copying mechanism employs a sophisticated system of two independent proofreading devices to detect and fix errors. On average, a mistake slips past the proofreaders only once for every 10 billion bases copied!Mark Lorch, Biochemistry: A Very Short Introduction (New York, Oxford University Press, 2021), 83. Biochemist Mark Lorch likens this astonishing fidelity to “typing out copies of the complete works of Shakespeare and making just one typographical error in every 2,000 copies.”Mark Lorch, Biochemistry: A Very Short Introduction (New York, Oxford University Press, 2021), 77. Nevertheless, the DNA copying mechanism does produce errors on rare occasions, as it types out copies at the astounding rate of nearly 1,000 bases per second.Mark Lorch, Biochemistry: A Very Short Introduction (New York, Oxford University Press, 2021), 79-80. More frequently, the original DNA is damaged by radiation or toxic chemicals, so the copying mechanism has to repair the damage by inserting new base pairs, perhaps different from the old. Such “mistakes” resulting from malfunctioning machinery or damaged DNA are called mutations.
There are many kinds of mutations, all of which are thought to play some role in the evolution of life. Here are several of the most common:
In a substitution mutation, a single nucleobase is replaced with another. These mutations might have little or no effect, or they might have dramatic effects, depending on where they occur. For example, if the letter “G” in the codon CAG is replaced with “A,” this mutation will have no effect at all, since CAG and CAA both code for the same amino acid, glutamine. However, if the letter “C” in CAG is replaced with “T,” the result could be disastrous, because TAG is a stop codon.
Deletion mutations occur when bases are removed from a DNA sequence. Similarly, insertion mutations occur when extra bases are added. Both deletion and insertion mutations typically have severe consequences, especially when the number of inserted or deleted bases isn’t divisible by 3. Since the genetic code uses 3-letter codons, all of the subsequent codons will be misread. For example, consider the sequence ATGCAGCAGTAG. The cell interprets this as a start codon (ATG) followed by two glutamine codons (CAG) and a stop codon (TAG). Deleting the first “C” from the sequence yields ATGAGCAGTAG, which the cell will interpret as a start codon start codon (ATG) followed by the codons AGC and AGT, neither of which was present in the original sequence. Insertion or deletion mutations that cause the cell to misread subsequent codons are called frameshift mutations.
In a gene duplication mutation, a segment of DNA is copied more than once, so the resulting genome inherits multiple copies of the gene or genes located in that segment. Sometimes, an extra copy of an entire chromosome is produced. Polyploidy, the condition of having extra copies of a whole chromosome, is especially common in plants.
When mutations occur in a single-celled organism, the altered DNA will be passed to its descendants as well. Similarly, if mutations occur in the gametes of sexually-reproducing organisms (or in the germ cells that produce gametes), the offspring may inherit those mutated genes. Randomly-occurring mutations are presumed to be the source of new genes and alleles, which may be preserved by natural selection, allowing for greater diversity than would be possible with genetic recombination alone.