Evolution__3rd_Edition

178 PART 2 / Evolutionary Genetics
Selectionists predict rapid finetuning
adjustments in genes ...
. . . but that theory is implausible
for non-coding DNA
probably change the enzyme’s activity. Because the enzyme is relatively well adapted,
the change is likely to be for the worse. It may well spoil the enzyme’s function. In other
parts of the molecule it may matter less what amino acid occupies a site, and a change is
more likely to be neutral. The proportion of mutations that are neutral will be lower for
the functionally constrained regions. Therefore, if the total mutation rate is similar
throughout the enzyme, the number of neutral mutations will be lower in the active
site. The evolutionary rate will then be lower too.
What is the selective explanation? The answer is usually expressed in terms of
Fisher’s (1930) model of adaptive evolution. We shall look at that model in Section
10.5.1 (p. 266). The model predicts that small, fine-tuning changes are more likely
to improve the quality of adaptation than large changes. We could make an analogy
with a radio. Biological molecules are fairly well adapted, but need to change from time
to time to keep up with environmental change. This corresponds to a radio that is
tuned to a station, but may wander out of tune from time to time as the signal changes.
Most of the changes to the radio will be small, fine-tuning adjustments; a large jerk on
the tuning knob would usually make things worse.
Mutations in a protein’s active site will tend to have large effects; mutations in the
outlying regions will have smaller effects. A change in amino acid in the active site is a
virtual macromutation, which will almost always make things worse; natural selection
will only rarely favor amino acid changes. But a similar change in the less functionally
constrained parts may have more chance of being a small fine-tuning improvement
which natural selection would favor. Selection will then more often favor changes in
the less constrained regions of molecules, because there is more scope for fine tuning in
those parts.
For amino acid changes in protein evolution, the neutralist and selectionist explanations
are both possible. There was a controversy between the two in the 1970s and
1980s, and that controversy has never been settled. However, since the 1980s, interest
has shifted more to DNA. For the DNA evidence a particularly the rapid evolution
in synonymous sites and in pseudogenes a the selectionist explanation has few, or
no, supporters. There is no evidence that the rapid evolution of these regions of DNA
is due to exceptionally rapid, adaptive fine tuning. Pseudogenes are, after all, functionless
and it is difficult to see what adaptation could be fine tuned within them.
Some biologists favor the full neutralist view, according to which evolution at both
synonymous and non-synonymous sites is mainly neutral. The slower evolution at
non-synonymous sites is then because many amino acid changes are disadvantageous.
Other biologists accept the neutralist view for synonymous sites and pseudogenes,
but remain undecided whether amino acid changes are driven more by drift or positive
selection.
7.7 Conclusion and comment: the neutralist paradigm shift
Arguably, the view of evolutionary biologists about molecular evolution has shifted
since the 1980s. When Kimura, King and Jukes first suggested the neutral theory in
1968 and 1969, they did so for protein evolution. The neutral theory was controversial
..