Dna

Gene

New stop codon due to mutation

Original stop codon

Shortened protein

Degradation

Shortened protein chain cannot fold properly (Fig. 13.05). Such misfolded proteins are detected and degraded by the cell (see Ch. 8). The result, in practice, is normally the total absence of this particular protein. Nonsense mutations are often lethal if they affect important proteins.

Deletions may remove critical segments of DNA or largely functionless regions of DNA.

Deletion Mutations Result in Shortened or Absent Proteins

Mutations that remove one or more bases are known as deletions and those that add extra bases are known as insertions. Clearly, the effect of a deletion (or insertion) depends greatly on how many bases are removed (or inserted). In particular, we should distinguish between point mutations where one (or a very few) bases are affected, and gross deletions and insertions that affect long segments of DNA. Point deletions and insertions may have major effects due to disruption of the reading frame—see below. Here we will consider the effects of larger deletions.

Deletions are indicated by the symbol D or by DE. Thus D(argF-lacZ) or DE(argF-lacZ) indicates a deletion of the region (of the E. coli chromosome in this case) from the argF to the lacZ gene. Obviously, deletion of the DNA sequence for a whole gene means that no mRNA and no protein will be made (Fig. 13.06). If the protein is essential, then the deletion will be lethal. Large deletions may remove part of a gene, an entire gene or several genes. Deletions may also remove part or all of the regulatory region for a gene. Depending on the precise region removed, gene expression may be decreased or increased. For example, a deletion that removes the binding site for a repressor may result in a large increase in activity of the gene in question. Thus loss of DNA may result in elevated activity. Again, deletions may remove largely func-tionless DNA, such as the non-coding sequences between genes or the introns found within genes. In this case, the effects may be small or marginal.

Deletion mutations are surprisingly frequent. About 5 percent of spontaneous mutations in bacteria such as E. coli are deletions. Although bacteria lack introns and the intergenic spacer regions are very short, it is still possible to generate non-lethal deletions of considerable size. The main reason is that many genes are needed only under certain limited environmental conditions. Thus deletions of the entire lac operon in E. coli prevent the organism from using lactose as a source of carbon, yet have no other deleterious effects.

Insertion Mutations Commonly Disrupt Existing Genes 341

Original DNA Gene

Deletion of ' these areas

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