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Griffiths AJF, Miller JH, Suzuki DT, et al. An Introduction to Genetic Analysis. 7th edition. New York: W. H.
Freeman; 2000.

Mutant types

The phenotypic consequences of mutation may be so subtle as to require refined biochemical

techniques to detect a difference from the phenotype conferred by the wild-type allele.
Alternatively, the mutation may be so severe as to produce gross morphological defects or death.
A rough classification follows, based only on the ways in which the mutations are recognized.
This classification is not meant to be complete. Furthermore, the various ways of categorizing
mutations often overlap.

Morphological mutations
Morph means “form.” Morphological mutations affect the outwardly visible properties of an
organism, such as shape, color, or size. Albino ascospores in Neurospora, curly wings in
Drosophila, and dwarf peas are all morphological mutations. Some additional examples of
morphological mutants are shown in Figure 15-9.

Figure 15-9

Eight morphological mutations of Drosophila, and the wild

type for comparison. Most of the mutant phenotypes are self-
explanatory; bithorax is an abnormality of the thorax
featuring small wings instead of balancers; the most
prominent feature of dichaete (more...)

Lethal mutations
A new lethal mutant allele is recognized by its effects on the survival of the organism.
Sometimes a primary cause of death from a lethal mutation is easy to identify (for example, in
certain blood abnormalities). But often the cause of death is hidden, and the mutant allele is
recognizable only by its effects on viability. An example of a lethal mutation is shown in Figure
15-10.

Figure 15-10

Phenotypes of the wild type (left) and a mutation affecting

plumage of Japanese quail (right). This mutation arose in a
laboratory colony of quail and could be maintained as an
interesting subject for genetic analysis. However, if such a
mutation had (more...)

Conditional mutations
In the class of conditional mutations, a mutant allele causes a mutant phenotype in only a certain
environment, called the restrictive condition, but causes a wild-type phenotype in some
different environment, called the permissive condition. Geneticists have studied many
temperature-conditional mutations. For example, certain Drosophila mutations are known as
dominant heat-sensitive lethals. Heterozygotes (say, H
+/H) are wild type at 20°C (the permissive
condition) but die if the temperature is raised to 30°C (the restrictive condition).
Many mutant organisms are less vigorous than their normal counterparts and thus more
troublesome as experimental subjects. For this reason, conditional mutants are useful because
they can be grown under permissive conditions and then shifted to restrictive conditions for
study. Another advantage of conditional mutations is that they allow the determination of a
developmental sensitive period at which specific time the gene acts. In these studies, organisms
carrying some specific conditional mutation are shifted from permissive to restrictive conditions
at different times in the course of development. Some shifts will lead to mutants, others to wild
types, and from these results the sensitive period of gene action is assessed.

Biochemical mutations
Microbial cultures are convenient material for the study of biochemical mutations, which are
identified by the loss or change of some biochemical function of the cells. This change typically
results in an inability to grow and proliferate. In many cases, however, growth of a mutant cell
can be restored by supplementing the growth medium with a specific nutrient. Microorganisms,
by and large, are prototrophic: they can exist on a substrate of simple inorganic salts and an
energy source; such a growth medium is called a minimal medium. Biochemical mutants,
however, often are auxotrophic: they must be supplied certain additional nutrients if they are to
grow. For example, one class of biochemically mutant fungi will not grow unless supplied with
the nitrogenous base adenine. They are called ad mutations, whereas the wild-type allele is ad
+.
Mutant ad alleles determine the auxotrophic, adenine-requiring phenotype. The practical method
of testing for the auxotrophic or prototrophic phenotype is shown in Figure 15-11.

Figure 15-11

Testing strains of Neurospora crassa for auxotrophy and

prototrophy. In this experiment, the test utilizes 20 progeny
from a cross of an adenine-requiring auxotroph and a leucine-
requiring auxotroph. Genotypically, the cross is ad · leu
(more...)

Although microbial cultures are used for experimental induction of biochemical mutations, we
should note that many human hereditary diseases are biochemical mutations defective in some
step of cellular chemistry. The expression inborn errors of metabolism has been used to
describe such biochemical disorders. Phenylketonuria and galactosemia are two examples.

Loss-of-function mutations
Generally, loss-of-function (null) mutations are found to be recessive. In a wild-type diploid cell,
there are two wild-type alleles of a gene, both making normal gene product. In heterozygotes (the
crucial genotypes for testing dominance or recessiveness), the single wild-type allele may be able
to provide enough normal gene product to produce a wild-type phenotype. In such cases, loss-of-
function mutations are recessive. In some cases, the cell is able to “upregulate” the level of
activity of the single wild-type allele so that in the heterozygote the total amount of wild-type
gene product is more than half that found in the homozygous wild type. However, some loss-of-
function mutations are dominant. In such cases, the single wild-type allele in the heterozygote
cannot provide the amount of gene product needed for the cells and the organism to be wild type.
The action of loss-of-function mutations is represented diagrammatically in Figure 15-12a and b.

Figure 15-12
 (a) Mutation m has completely lost its function (it is a null mut
heterozygote, wild-type gene product is still being made, and o
is enough to result in a wild-type phenotype, in which case, m
recessive. If the (more...)

Gain-of-function mutations
Because mutation events introduce random genetic changes, most of the time they result in loss
of function. The mutation events are like bullets being fired at a complex machine; most of the
time they will inactivate it. However, it is conceivable that in rare cases a bullet will strike the
machine in such a way that it produces some new function. So it is with mutation events;
sometimes the random change by pure chance confers some new function on the gene. In a
heterozygote, the new function will be expressed, and therefore the gain-of-function mutation
most likely will act like a dominant allele and produce some kind of new phenotype. Gain of
function is represented in Figure 15-12c.

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