Mutations in DNA

Consider again the earlier discussion of DNA replication. When the double-stranded molecule uncoils and the paired bases disjoin, the liberated bases can then attach to new nucleotides. Recall also that adenine always pairs with thymine, and guanine always pairs with cytosine. Well, almost always. If this pairing were completely free of error, there would be no evolution. Everything would always remain the same. But errors in replication do occur. Such errors are called mutations. While errors in replication may explain evolution, most such mutations do not confer any advantage. In fact, most are harmful.

There are several kinds of mutations. One type of error that can have major consequences is called an insertion; an extra nucleotide is put into the chain. Suppose a segment of DNA should have the following sequence of bases:

GTAACCCGGTI'TGCA

Although there are no breaks or spaces between the triplets (codons) in a DNA molecule, inserting breaks on paper facilitates visualization. Thus, the preceding sequence may be represented as follows:

GTA

ACG

CGG

TTT

GCA

The m-RNA that would be fabricated on this sequence would be as follows:

CAU

UGC

GCC

AAA

CGU

representing the codons for:

histidine-tryptophane-alanine-lysine-arginine

If a guanine were to be inserted between the second and third bases of the DNA chain (at the arrow), changes would occur all along the line. The triplets would then be as follows:

GTG AAC CCG GTT TGC A—

↑

The m-RNA would then be codified as follows:

CAC

UUG

GGC

CAA

ACG

The following sequence of amino acids would then result:

histidine-leucine-glycine-glutamine-threonine

The first amino acid in the series, histidine, is not changed, because both CAU and CAC represent the same amino acid. The others, however, are changed.

Deletion is another kind of mutation. Assume the same sequence of DNA bases as noted earlier:

GTA ACC CGG TTT

↑

If the third base in the chain (see arrow) were to be knocked out (deleted), the sequence would then be as follows:

GTA CCC GGT TT−

The deletion does not alter the first triplet, because a neighboring adenine takes the place of the adenine deleted from the first triplet. The other codons, however, are altered, and the m-RNA sequence becomes:

CAU GGC CCA AA−

Thus, the amino acid sequence is changed from histidine-tryptophane-alanine- lysine to histidine-lysine-proline. Obviously, a small alteration of DNA can result in great changes in protein structure.

Another type of DNA alteration called substitution appears to have lesser consequences. If the original segment of DNA were to be changed by replacing a nucleotide with one of a different kind, only one amino acid in the chain would be changed. For example, consider a substitution made at the third position in our original chain:

GTA ACC CGG TTA

GTC ACC CGG TTA

The m-RNA in the first part, then, changes from CAU to CAG the amino acid histidine is replaced with glycine.(Other anomalous chromosomal alterations that can affect protein synthesis [such as inversions, crossing over, and polyploidy] are described in chapter 3 on mitosis and meiosis.)