The molecular basis of mutations

Any alteration made to the DNA sequence of an organism is called a mutation. This may or may not have an effect on the phenotype (physically manifested properties) of the organism. It may for example enable bacteria to grow without the need for a particular growth supplement, or confer resistance to an antibiotic. Just how this happened was for many years a source of debate. Since the mutant forms only became apparent after the change in conditions (e.g. withdrawal of a nutrient, addition of antibiotic), have some of the bacteria been induced to adapt to the new conditions, or are mutant forms arising all the time at a very low frequency, and merely selected by the environmental change? In 1943, Salvador Luria and Max Delbrück devised the fluctuation test to settle the matter (see Box 11.6). Results of the fluctuation test together with other evidence led to the understanding that mutations occur spontaneously in nature at a very low frequency. As we shall see later on in this section, however, they can also be induced by a variety of chemical and physical agents. Any change to the DNA sequence is heritable, thus mutations represent a major source of evolutionary variation. Bacteria make marvellous tools for the study of mutations because of their huge numbers and very short generation times.

Since the DNA sequence of a gene represents highly ordered coded information, most mutations have a neutral or detrimental effect on the organism's phenotype, but occasionally a mutation occurs which confers an advantage to an organism, making it better able to survive and reproduce in a particular environment. Mutants that are favoured in this way may eventually become the dominant type in a population, and, by steps like this, evolution gradually takes place.

Mutations occur spontaneously in any part of an organism's genome. Spontaneous mutations causing an inactivation of gene function occur in bacteria at the rate of about one in a million for a given gene at each round of cell division. Most genes within a given organism show similar rates of mutation, relative to their gene size; clearly a larger 'target' will be 'hit' more often than a small one.

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