Evolution__3rd_Edition

46 PART 1 / Introduction
Figure 3.2
Evolution of drug resistance in
HIV. 3TC is a nucleoside
inhibitor and it resembles C.
(a) Drug-susceptible reverse
transcriptase binds both
3TC and C. When 3TC is
incorporated into a growing
DNA chain, it inhibits further
replication. (b) Drug resistance
is achieved by the evolution of
reverse transcriptase that binds
only C, and not 3TC.
HIV evolves drug resistance
Other examples exist too
(a) 3TC-susceptible HIV
RNA
DNA
RNA
DNA
(b) 3TC-resistant HIV
RNA
DNA
3TC
C
C
Reverse
transcriptase
Reverse
transcriptase
an AIDS patient is a microcosm of the process that has caused much of the diversity of
life on Earth.
The evolution of drug resistance can be followed at the molecular level. The change
from 3TC-susceptible HIV to 3TC-resistant HIV is achieved by a change in one codon
in the gene that codes for reverse transcriptase. The amino acid methionine is changed
to one of three other amino acids. The methionine is in a part of the reverse transcriptase
that interacts with the nucleosides. Probably what is happening is that the normal
reverse transcriptase is a relatively undiscriminating enzyme that does not distinguish
between C and 3TC. The change makes the enzyme more discriminating, such that it
binds C but does not bind 3TC. The virus can then reproduce in the presence of 3TC
(Figure 3.2). The superior discrimination is paid for by slower reproduction, and the
3TC-resistant version of HIV is therefore at a disadvantage when the drug is not present.
In the presence of the drug it is adaptive for HIV to reproduce slowly but carefully.
In the absence of the drug it is adaptive to reproduce faster, and in a molecularly carefree
manner.
Drug resistance in HIV is one of many examples in which evolution has been
observed on a small scale. In other examples, evolutionary change has been detected in
periods of years rather than days. In Section 5.7 (p. 108) we look at the famous example
of evolution in the peppered moth (Biston betularia). In Section 9.1 (p. 223) we look at
changes in the average beak size of a population of a finch species in the Galápagos
islands. In Section 13.4.1 (p. 359) we look at geographic variation in the house sparrow
C
3TC
C
3TC
..