Evolution__3rd_Edition

162 PART 2 / Evolutionary Genetics
Box 7.1
Genetic Loads and Kimura’s Original Case for
the Neutral Theory
Two of Kimura’s (1968, 1983) three original arguments for
the neutral theory made use of a general concept called “genetic
load.” Genetic load is a property of a population and is defined as
follows. The population will contain a number of genotypes, and
each genotype has a certain fitness. We identify the genotype, of
those present in the population, that has the highest fitness, and
assign that genotype a relative fitness of one. All the other
genotypes will have fitnesses of less than one. We also measure
the average fitness of the whole population; it is just the fitness
of each genotype multiplied by its frequency and is called mean
fitness (Section 5.6, p. 105). Mean fitness is conventionally
symbolized by D. The general formula for genetic load (L)
is then
L = 1 − D
If all the individuals in the population have the optimal genotype,
D = 1 and the load is zero. If all but one have a genotype of zero
fitness, D = 0 and L = 1. Genetic load is a number between 0
and 1 and it measures the extent to which the average individual
in a population is inferior to the best possible kind of individual,
given the range of genotypes in the population. To be exact, the
genetic load equals the relative chance that an average individual
will die before reproducing because of the disadvantageous genes
that it possesses.
Genetic load can exist for several reasons. Kimura’s original
argument considered substitutional load and segregational load.
Substitutional load arises when natural selection is substituting one
(superior) allele for another (inferior) allele. While the inferior allele
exists in the population, mean fitness is lower than if all individuals
had the superior allele. The substitutional load is mathematically
equivalent to another concept, defined by Haldane (1957), and
called the “cost of natural selection.”
Kimura, following Haldane, suggested that the rate of evolution
has an upper limit. A favorable mutation might arise; initially it is
a single copy in the population. At a very theoretical extreme,
the favorable mutation could rise to a frequency of 100% in the
population in three generations. In the first two generations, all
individuals lacking a copy of the favorable mutation would have
to die without breeding (except one in the first generation to
provide a mate for the mutant). In the third generation, all
individuals lacking two copies of the favorable gene would
have to die without breeding. The mutation would then
have spread to a frequency of 100%.
Such rapid evolution is unlikely for various reasons, but the
reason discussed by Haldane and Kimura was that the population
would be driven down to such a low level that it would go extinct.
A real population is unlikely to persist if it is cut down to one
breeding pair. Moreover, a population certainly could not persist if
two such mutations arose at separate loci, because then even the
individuals who survived because they had one of the mutations
would die for want of the other. Everyone would be dead. More
realistic evolution will proceed at a lower rate, because the
population must continue to exist in reasonable numbers while
natural selection substitutes superior alleles. Haldane (1957)
suggested an upper limit on the rate of evolution of about one
gene substitution per 300 generations.
Molecular evolution proceeds at a far higher rate than this.
When Kimura (1968) first estimated the total rate of molecular
evolution in an average mammal species he derived a figure of one
substitution every two generations. However, he only had evidence
from amino acids. We now know that the rate of synonymous
change is even higher. The full rate of DNA evolution is more like
eight substitutions per year, or one substitution every 1.5 months
(Hughes 1999, p. 41). The rate of molecular evolution is clearly far
higher than Haldane’s estimated upper limit. Kimura concluded that
most molecular evolution could not be driven by natural selection.
Molecular evolution must be driven instead by random drift.
Random drift creates no genetic load, because all the genotypes
concerned have equal fitness.
The argument with segregational load is similar. Segregational
load arises when a polymorphism exists, maintained by
heterozygous advantage (Section 5.12, p. 123). (Segregational load
may or may not exist with polymorphisms maintained by frequencydependent
selection, but the original arguments considered
heterozygous advantage.) With heterozygous advantage, the
fitnesses of the genotypes are:
Genotype AA Aa aa
Fitness 1 − s 1 1 − t
The population has a genetic load because the population
cannot consist purely of heterozygotes. Even if a population did
temporarily consist only of heterozygotes, they would produce
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