Essential Cell Biology 5th edition

674 CHAPTER 19 Sexual Reproduction and Genetics
that encodes a gap-junction protein; see Figure 20–28) occurs in about
one in 4000 births, but about one in 30 of us are carriers of a loss-offunction
mutant allele of the gene.
GENETICS AS AN EXPERIMENTAL TOOL
Unraveling how chromosomes shuttle genetic information from one generation
to the next did more than demystify the basis of inheritance: it
united the science of genetics with other life sciences, from cell biology
and biochemistry to physiology and medicine. Genetics provides a
powerful way to discover what specific genes do and how variations in
those genes underlie the differences between one species and another or
between individuals within a species. Such knowledge also has practical
benefits, as understanding the genetic and biological basis of diseases
can help us to better diagnose, treat, and prevent them.
In this section, we outline the classical genetic approach to identifying
genes and determining how they influence the phenotype of experimental
organisms such as yeast or flies. The process begins with the generation
of a very large number of mutants and the identification of those
rare individuals that show a phenotype of interest. By analyzing these
rare mutant individuals and their progeny, we can track down the genes
responsible and work out what these genes normally do—and how mutations
that alter their activity affect how an organism looks and behaves.
The Classical Genetic Approach Begins with Random
Mutagenesis
Before the advent of DNA technology (discussed in Chapter 10), most
genes were identified and characterized by observing the processes disrupted
when the gene was mutated. This type of analysis begins with the
isolation of mutants that have an interesting or unusual phenotype: fruit
flies that have white eyes or curly wings or that become paralyzed when
exposed to high temperatures, for example. Working backward from
the abnormal phenotype, one then determines the change in DNA that
is responsible. This classical genetic approach—searching for mutant
phenotypes and then isolating the responsible genes—is most easily
performed in model organisms that reproduce rapidly and are amenable
to genetic manipulation, such as bacteria, yeasts, nematode worms,
zebrafish, and fruit flies. A few of the principles behind this classical
approach are outlined in Panel 19−1, (p. 675).
Although spontaneous mutants with interesting phenotypes can be found
by combing through a collection of thousands or millions of organisms,
the process can be made much more efficient by generating mutations
artificially with agents that damage DNA, called mutagens. Different mutagens
generate different types of DNA mutations (Figure 19−31). Not all
mutations will lead to a noticeable change in phenotype. But by treating
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nucleotide substitution
Figure 19−31 DNA-damaging agents
produce various types of mutations.
Some common types of mutation are shown
here. Different mutagens each produce
a characteristic spectrum of mutations.
Other types of mutation involve changes
in larger segments of DNA, including
deletions, duplications, and chromosomal
rearrangements (not shown).
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normal
gene
sequence
TREATMENT WITH
DNA-DAMAGING
AGENT (MUTAGEN)
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nucleotide insertion
nucleotide deletion
insertion of
multiple nucleotides
deletion of
multiple nucleotides