Essential Cell Biology 5th edition

676 CHAPTER 19 Sexual Reproduction and Genetics
large numbers of organisms with mutagens, collections of mutants can
be generated quickly, increasing the odds of finding an interesting phenotype,
as we discuss next.
Genetic Screens Identify Mutants Deficient in Specific
Cell Processes
A genetic screen typically involves examining many thousands of mutagenized
individuals to find the few that show a specific altered phenotype
of interest. To search for genes involved in cell metabolism, for example,
one might screen mutagenized bacterial or yeast cells to pick out those
that have lost the ability to grow in the absence of a particular amino acid
or other nutrient (see Figure 9–5).
Even genes involved in complex phenotypes, such as social behavior,
can be identified by genetic screens in multicellular organisms. For example,
by screening for worms that feed alone rather than in clusters as do
wild-type individuals, scientists identified and isolated a gene that affects
this “social behavior” (Figure 19−32).
Advances in modern technologies have made it possible to carry out
high-throughput genetic screens using large collections of individuals,
each of which has a different gene inactivated. Such mutant collections
can often be screened using automated robots. For example, investigators
have made use of RNA interference (explained in Figure 8−28) to
generate a collection of nematode worms in which the activity of every
protein-coding gene has been disrupted, with each worm being deficient
in just one gene. These collections can be screened rapidly for dramatic
changes in phenotype, such as stunted growth, uncoordinated movement,
decreased fertility, or impaired embryonic development (Figure
19−33). Using this strategy, the genes needed to produce a particular
characteristic can be identified.
Conditional Mutants Permit the Study of Lethal
Mutations
Genetic screens are a powerful approach for isolating and characterizing
mutations that are compatible with life—those that change the appearance
or behavior of an organism without killing it. A problem arises,
however, if we wish to study essential genes—those that are absolutely
required for fundamental cell processes, such as RNA synthesis or cell
division. Defects in these genes are usually lethal, which means that special
strategies are needed to isolate and propagate such mutants: if the
mutants cannot be bred, their genes cannot be studied.
Figure 19−32 Genetic screens can be
used to identify mutations that affect
an animal’s behavior. (A) Wild-type
C. elegans dine alone. (B) Mutant worms
engage in social feeding. (Courtesy of
Cornelia Bargmann.)
(A)
(B)
1 mm