Essential Cell Biology 5th edition

678 CHAPTER 19 Sexual Reproduction and Genetics
then screened for cells that stopped making DNA when they were warmed
from 30°C to 42°C. Similarly, temperature-sensitive yeast mutants were
used to identify many of the proteins involved in regulating the cell cycle
(see How We Know, pp. 30–31) and in transporting proteins through the
secretory pathway (see Figure 15−28).
The DNA technologies discussed in Chapter 10 have made it possible to
construct an entirely different type of conditional mutant—one in which
the gene of interest is engineered such that it can be deleted at a particular
time in development or in a particular tissue (see Figure 10–30).
Essential genes—for example, those whose complete inactivation would
cause an organism to die early in development—can be studied in this
way because the organism can be allowed to develop past the critical
period before the gene is deleted. This strategy is particularly useful for
studying genes that are active in many different tissues, as the role they
play in each one can be independently assessed.
Figure 19−35 A complementation test
can reveal that mutations in two different
genes are ECB5 responsible e19.35/19.35 for the same
abnormal phenotype. When an albino
(white) bird from one strain is bred with an
albino from a different strain, the resulting
offspring have normal coloration. This
restoration of the wild-type plumage
implies that the two white breeds lack
color because of recessive mutations in
different genes. (From W. Bateson,
Mendel’s Principles of Heredity, 1st ed.
Cambridge, UK: Cambridge University
Press, 1913.)
A Complementation Test Reveals Whether Two
Mutations Are in the Same Gene
A large-scale genetic screen can turn up many mutant organisms with
the same phenotype. These mutations might affect the same gene or
they might affect different genes that function in the same process. How
can we distinguish between the two? If the mutations are recessive, a
complementation test can reveal whether they affect the same or different
genes.
In the simplest type of complementation test, an individual that is
homozygous for one recessive mutation is mated with an individual that
is homozygous for the other mutation. If the two mutations affect the
same gene, the offspring will show the mutant phenotype, because they
carry only defective copies of the gene in question. If, in contrast, the
mutations affect different genes, the resulting offspring will show the
normal, wild-type phenotype, because they will have one normal copy
(and one mutant copy) of each gene (see Panel 19−1, p. 675).
Whenever the normal phenotype is restored in such a test, the alleles
inherited from the two parents are said to complement each other (Figure
19−35). For example, complementation tests on mutants identified during
genetic screens have revealed that five genes are required for yeast
cells to digest the sugar galactose, that 20 genes are needed for E. coli
to build a functional flagellum, and many hundreds are essential for the
normal development of an adult nematode worm from a fertilized egg.
EXPLORING HUMAN GENETICS
Genetic screens in model experimental organisms have been spectacularly
successful in identifying genes and relating them to various
phenotypes, including many that are conserved between these organisms
and humans. But the same approach cannot be used in humans.
Unlike flies, worms, yeast, and bacteria, humans do not reproduce rapidly.
More importantly, intentional mutagenesis in humans is out of the
question for ethical reasons.
Nonetheless, humans are becoming increasingly attractive subjects for
genetic studies. Because the human population is so large, spontaneous
nonlethal mutations have arisen in all human genes—many times
over. A substantial proportion of these nonlethal mutations remain in
the genomes of present-day humans, and the most harmful of these
mutations are discovered when the affected individuals call attention to
themselves by seeking medical help—a uniquely human behavior.