Evolution__3rd_Edition

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The original neutral theory has been
modified
CHAPTER 7 / Natural Selection and Random Drift 159
neutral” theory of molecular evolution. Kimura’s original theory considered only
purely neutral mutations, with a selection coefficient of zero. His modern followers
also consider mutations with small positive or negative selection coefficients. Because
drift is more powerful with small population sizes (Section 6.1, p. 138), these nearly
neutral mutations are influenced more by drift in small populations and more by
selection in large populations. The mutations become effectively neutral, or nonneutral,
depending on population size.
Secondly, the original neutral theory made a global claim about all molecular evolution.
The neutral theory suggested that almost all molecular evolution is driven by
neutral drift. Now the theory has been refined. Some parts of the DNA appear to evolve
by neutral drift, but the relative contributions of selection and drift in other parts of
the DNA are less clear. The stark contrast between (a) and (b) in Figure 7.1 has been
modified by 30 years of accumulated evidence.
The crucial difference between the selectionist and neutral theories of molecular
evolution lies in the relative frequencies of neutral and selectively advantageous mutations.
The direct way to test between them should simply be to measure the fitnesses
of many genetic variants at a locus, and count the numbers with negative, neutral, or
positive selection coefficients under certain environmental conditions. But the controversy
has not been settled in this way. To measure the fitness of even one common
genetic variant is a major research exercise, and to measure the fitnesses of many rare
variants would be practically impossible.
In the first half of this chapter we shall look at three lines of less direct evidence that
were originally used by Kimura, and King and Jukes, to argue for the importance of
neutral drift in molecular evolution.
1. The absolute rate of molecular evolution and degree of polymorphism, both of
which have been argued to be too high to be explained by natural selection.
2. The constancy of molecular evolution, which has been argued to be inconsistent
with natural selection.
3. The observation that functionally less constrained parts of molecules evolve at a
higher rate, which has been argued to be the opposite of what the theory of natural
selection would predict.
Observation 1 is now of little influence. The molecular clock (observation 2) is not
merely still influential, but has become the basis of a major research program in evolutionary
biology. The relation between functional constraint and rate of evolution
(observation 3) is also important. It has turned out that observation 3 can be studied
more powerfully with DNA sequences, which have become increasingly available since
the 1980s, than in protein sequences, which were used in the 1960s and 1970s.
In the second half of the chapter we shall look at some additional ways of testing
between drift and selection that have become possible in the genomic era.
7.2 Rates of molecular evolution and amounts of genetic
variation can be measured
Rates of evolution are estimated from the amino acid sequence of a protein, or
nucleotide sequence of a region of DNA, in two or more species. For any two species,