THE GENETiCAl THEoRy of NATuRAl SElECTioN 131
with a hypothetical population without mutations. Mutations that reduce indi-
vidual fitness to different degrees have the same mutation load when they are at
mutation-selection equilibrium, because of the balance between their harmful-
ness and their frequency. This means that the effect of a deleterious mutation on
a population’s fitness is unaffected by s, that is, the size of the mutation’s effect
on fitness. The load is determined only by the rate at which mutations enter the
population. The load caused by deleterious mutation at a single locus is simply 2μ.
For example, with mutation rate of μ = 10–6, the mean fitness of the population is
reduced by a very small amount: L = 0.000002.
But while mutation rates at individual loci are typically very small, eukary-
otes (including humans) have a great many loci. We use U to represent the total
mutation rate across the genome for deleterious alleles. That is, U is the average
number of new deleterious mutations that are added to the genome each genera-
tion. Recent studies suggest that U in humans is about two new deleterious muta-
tions per genome per generation [24]. A result is that each of us carries hundreds
of deleterious mutations at various loci scattered throughout the genome [1, 15].
Their combined impact on mean population fitness (i.e., the total mutational load)
depends on how the effects of deleterious mutations at different loci combine
to determine overall fitness, which is very difficult to estimate accurately. If we
assume that mutations have independent effects on fitness, the mutation load is:L = 1 – e–U (5.10)where e is a mathematical constant approximately equal to 2.7.
The genome-wide mutation rate estimated for humans is U = 2, so this equation
says that the load is L = 0.86. This implies that 86 percent of the potential mean
fitness in humans is lost to the effects of deleterious mutations, either by mortality
or reduced fertility.
Do deleterious mutations really have that big an impact on human health?
The actual effect is likely much smaller because it also depends on factors such
as demography and how individuals compete for resources. Furthermore, the
assumption that mutations have independent fitness effects may not be correct
[27]. Nevertheless, deleterious mutations do contribute to senescence and genetic
disease in humans and other species (see Chapter 11). Less than half of eggs that
are fertilized lead to a successful birth [29], and it is possible that this high rate
of mortality at the earliest stages of development is partly caused by deleterious
mutations.
What is the impact of modern health care on deleterious mutations? By sav-
ing individuals from genetic diseases, medical intervention does allow mutations
to be passed on that would have been eliminated by natural selection earlier in
human history. But population genetic theory tells us that the frequency of these
mutations will increase slowly, and many generations will pass before they become
much more common. Whether the end result will have a major impact on human
health is controversial [19, 24, 28].Go to the
Evolution Companion Website
EVoluTioN4E.SiNAuER.CoM
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