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Chapter: Genetics and Molecular Biology: Genetics

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Genetics Mutations

Historically, one reason for the study of genetics was to discover the chemical basis of heredity.

Mutations

Historically, one reason for the study of genetics was to discover the chemical basis of heredity. Naturally, the existence of mutations was necessary to the execution of the classical experiments in genetics, and an understanding of mutations will facilitate our study of these experi-ments. We have already covered the chemical basis of heredity and the basics of gene expression. Perhaps here we should explicitly state that a gene refers to a set of nucleotides that specifies the sequence of an RNA or protein. We will define mutation and in the next section mention the three basic types of mutations. In the following section we will review the classical genetic experiments before turning to recombina-tion.

A mutation is merely an inheritable alteration from the normal. It is an alteration in the nucleotide sequence of the DNA or, in the case of RNA viruses, an alteration in the nucleotide sequence of its genomic RNA. We already know that changes in coding portions of DNA may alter the amino acid sequences of proteins and that changes in noncod-ing regions of DNA have the potential for changing the expression of genes, for example by altering the strength of a promoter. Of course, any cellular process that makes use of a sequence of DNA can be affected by a mutation. The existence of mutations implies that the sequence of DNA in living things, including viruses, is sufficiently stable that most individuals possess the same sequence but sufficiently unstable that alterations do exist and can be found.

The terms wild-type, mutant, mutation, and allele are closely related but must be distinguished. Wild-type is a reference, usually found naturally. It can mean an organism, a set of genes, a gene, a gene product like a protein, or a nucleotide sequence. A mutation is an inheritable change from that reference. A mutant is the organism that carries the mutation. Two mutations are said to be allelic if they lie in the same gene. However, now that genes can be analyzed at the nucleotide level, in some situations alleles refers to nucleotides rather than to genes.

Until it became possible to sequence DNA easily, mutations could readily be identified only by their gross effects on the appearance of the cell or the shape, color, or behavior of an organism. Some of the most easily studied biological effects of mutations in bacteria and viruses were changes in the colony or plaque morphology. Other easily studied effects of mutations were the inability of cells to grow at low or high temperatures or the inability to grow without the addition of specific chemicals to the growth medium. Such readily observed properties of cells constitute their phenotype. The status of the genome giving rise to the phenotype is called the genotype. For example, the Lac- phenotype is the inability to grow on lactose. It can result from mutations in lactose transport, β-galactosidase enzyme, lac gene regulation, or the cells’ overall regulation of classes of genes that are not well induced if cells are grown in the presence of glucose. Such cells would have a mutation in any of the following genes: lacY, lacZ, lacI, crp, or cya.


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