mUTATIon AnD VARIATIon 95
There is substantial variation between the mutation rates of different regions
of the genome, and between different DNA bases. Transition mutations are those
between A and G, and between C and T. Transversion mutations are all the other
kinds (for example, between A and C). Even though there are twice as many pos-
sible transversion mutations, transition mutations are more common. In short, not
all mutations are equally likely. In that sense, mutation is not random.
Mutation is random, however, in a different and fundamental sense. Mutations
are random with respect to what will improve survival and reproduction. New
conditions do not increase the frequency of mutations that are beneficial in those
conditions. Geneticists have confirmed this fact experimentally, and it is important
for the following reason. We could imagine a world in which organisms respond
to increasing temperatures (for example) by increasing the frequency of mutations
that make them more heat tolerant. This kind of “directed mutation” would allow
organisms to adapt more rapidly to the changing conditions.
An elegant test of the directed mutation hypothesis is the famed replica plate
experiment done by Joshua and Esther Lederberg [14]. The bacterium Escherichia coli
is attacked by a virus called T1, but some cells carry a mutation that allows them to
resist the attack. The Lederbergs began by inoculating a petri plate with a culture
of E. coli that they started from a single cell that was not resistant to the virus. After
incubation, this “master plate” had a few hundred colonies on its surface, each of
which grew from a single cell in the original culture. A disk covered in velvet was
gently pressed to the surface of the plate, then gently pressed to the surface of
several other “replica plates” that had been sterilized. The velvet picked up a few
cells from each colony on the master plate, then transferred them to the replica
plates. The brilliance of this experimental design is that the spatial positions of the
colonies was the same on the master and the replica plates.
The next step of the experiment was to treat all of the plates with a culture of the
T1 virus. As expected, the virus killed almost all of the colonies. A small number
of colonies, however, survived. The Lederbergs showed that those colonies car-
ried a mutation for phage resistance: after they were transferred to new plates and
attacked again with T1 virus, those colonies still survived.
What can this experiment tell us about the randomness of mutation? Consider
the two hypotheses shown in FIGURE 4.19. Under hypothesis 1, the addition of
the virus induces resistance mutations in the bacteria. In that case, some colonies
should survive and some should not, depending on whether they are able to make
the adaptive mutation before they are killed. But crucially, there is no reason that
the particular colonies that survive on the replica plates should be the same. We
predict that the positions of the surviving colonies will vary between the plates.
Under hypothesis 2, resistance mutations occur randomly, whether the virus
is present or not. In this case, some of the colonies on the master plate will have
the mutation, even though they have never been in contact with the virus. Those
colonies will appear in the same locations on the replica plates. When the virus is
added to the replica plates, we predict that the colonies that survive will be in the
same locations.
The results of the Lederbergs’ experiment were clear: the same colonies sur-
vived the viral attacks. This shows clearly that the mutation for resistance to the
virus occurred in colonies on the master plate, before the mutation was favorable
to the bacteria. This experiment, and many more like it, give strong support to the
hypothesis that mutation is random with respect to what the environment favors.
A final point is that the environment can (and does) have important effects on
mutation rates. Exposure to radiation can increase a person’s mutation rate. But
the mutations that result will not be particularly good at improving our chance
of surviving the effects of radiation. A species becomes better at surviving in its04_EVOL4E_CH04.indd 95 3/23/17 8:55 AM