Download 16.1 X-Rays Were the First Environmental Agent

Robert J. Brooker - Genetica
Esperimento di genetica 16.1
X-Rays Were the First Environmental
Agent Shown to Cause Induced
Mutations
As shown in Table 16.5, changes in DNA structure can also be
caused by environmental agents, either chemical or physical agents.
These agents are called mutagens, and the mutations they cause are
referred to as induced mutations. In 1927, Hermann Müller devised
an approach to show that X-rays can cause induced mutations in
Drosophila melanogaster. Müller reasoned that a mutagenic agent
might cause some genes to become defective. His experimental
approach focused on the ability of a mutagen to cause defects in Xlinked genes that result in a recessive lethal phenotype.
To determine if X-rays increase the rate of recessive, X-linked
lethal mutations, Müller sought an easy way to detect the occurrence of such mutations. He cleverly realized that he had a laboratory strain of fruit flies that could make this possible. In particular,
he conducted his crosses in such a way that a female fly that inherited a new mutation causing a recessive X-linked lethal allele would
not be able to produce any male offspring. This made it very easy
for him to detect lethal mutations; he had to count only the number
of female flies that could not produce sons. To understand Müller’s
crosses, we need to take a closer look at a peculiar version of one of
the X chromosomes in a strain of flies that he used in his crosses.
This X chromosome, designated ClB, had three important genetic
alterations.
(Note: C and B are uppercase because they are inherited in a dominant manner, and l is lowercase because it is a recessive allele.)
A female fly that has one copy of this X chromosome would
have bar-shaped eyes, because bar is a dominant allele. Even
though this X chromosome has a recessive lethal allele, a female fly
can survive if the corresponding gene on the other X chromosome is
a normal allele. In Müller’s experiments, the goal was to determine
if exposure to X-rays caused a mutation on the normal X chromosome (not the ClB chromosome) that created a recessive lethal allele in any essential X-linked gene except for the gene that already
had a lethal allele on the ClB chromosome (Figure EG16.1.1). If a
recessive lethal mutation occurred on the normal X chromosome,
this female could survive because it would be heterozygous for recessive lethal mutations in two different genes. However, because
each X chromosome would have a lethal mutation, this female
would not be able to produce any living sons.
The steps in Müller’s protocol are shown in Figure EG16.1.2. He
began with wild-type males and exposed them to X-rays. These Xrays may mutate the X chromosome in sperm cells, resulting in a
recessive lethal allele. These males, and a control group of males
that were not exposed to X-rays, were then mated to females carrying the ClB chromosome. Daughters with bar eyes were saved from
this cross and mated to nonirradiated males. You should look carefully at this cross and realize that if these daughters also contained a
lethal allele on the X chromosome they inherited from their father
(e.g., an irradiated male in step 1), they would not be able to produce living sons.
THE HYPOTHESIS
The exposure of flies to X-rays will increase the rate of mutation.
THE DATA
Treatment of
Fathers of the
ClB Daughters
Control
X-ray treated
Number of ClB
Daughters
Crossed to
Normal Males*
1011
1015
Number
of Tubes
Containing
Any Offspring†
947
783
Number of
Tubes
with Female
Offspring but
Lacking Male
Offspring
1
91
*See step 4.
†The reason why these values are less than the numbers of mated ClB daughters is
because some crosses did not produce living offspring.
FI GU RE EG1 6 .1 .1 A st ra t egy t o de t e c t t he pre se nc e of
le t hal X-linke d m ut a t ions. X-rays may cause a recessive lethal
mutation to occur in the normal X chromosome. This female also contains another lethal allele in the ClB chromosome. Nevertheless, this
female could survive because it would be heterozygous for recessive
lethal mutations in two different genes. Because each X chromosome
would have a lethal mutation, this female would not be able to produce
any living sons.
© 2010 The McGraw-Hill Companies, S.r.l. - Publishing Group Italia
Robert J. Brooker - Genetica
Starting material: The female flies used in this study had one normal X chromosome and a ClB X chromosome. The male flies had a
normal X chromosome.
FI GU RE 1 6 .2 Evide nc e t ha t X -ra ys c ause m ut at ion.
© 2010 The McGraw-Hill Companies, S.r.l. - Publishing Group Italia
Robert J. Brooker - Genetica
INTERPRETING THE DATA
As shown in the data of Figure EG16.1.2, in the absence of X-ray
treatment, only 1 cross in approximately 1,000 was unable to produce male offspring. This means that the spontaneous rate for any
X-linked lethal mutation was relatively low. By comparison, X-ray
treatment of the fathers that gave rise to these ClB females resulted
in 91 crosses without male offspring. Because these females inherited their non-ClB chromosome from irradiated fathers, these results
indicate that X-rays greatly increase the rate of X-linked, recessive
lethal mutations. This conclusion has been confirmed in many subsequent studies, which have shown that the increase in mutation rate
is correlated with the amount of exposure to X-rays.
© 2010 The McGraw-Hill Companies, S.r.l. - Publishing Group Italia