Evolution, 4th Edition

130 CHAPTER 5

Deleterious Mutations

Some mutations increase fitness: they make individuals more resistant to a dis-

ease, say, or better able to digest a new food resource. But the vast majority of

mutations that have fitness effects are deleterious. Studies of the fitness effects of

mutations suggest that deleterious mutations are at least ten times more common

than beneficial mutations (see Fig ure 4.17). The injection of deleterious alleles into

populations by mutation has important evolutionary consequences.

A mutation-selection balance

Deleterious mutation is an important cause of genetic disease in humans and

other organisms. The famous American musician Woody Guthrie died at the age

of 55 of Huntington’s disease. This results from a dominant mutation that causes

degeneration of the central nervous system. In the United Kingdom, the muta-

tion is present in about 12 out of 100,000 people. More than 4000 genes have been

identified in humans that when mutated cause diseases such as Down syndrome,

cystic fibrosis, color blindness, and hemophilia. Selection that acts to remove del-

eterious mutations from a population is called purifying selection.

Why hasn’t purifying selection eradicated deleterious mutations that cause

these diseases? The answer is that they are being continually reintroduced. This

flow of new mutations into the population is offset by natural selection that acts

to eliminate them. This situation leads to a mutation-selection balance. Here it

is most convenient to use the mutation-free homozygote as the fitness reference,

and write the fitness of the mutant heterozygote as (1 – s). When the input of the

deleterious allele by mutation balances its removal by selection, the deleterious

mutation reaches an equilibrium frequency of

(5.9)

On the right side of the equation, μ is the mutation rate, that is, the probability

that a copy of the normal allele mutates to a deleterious allele in a given genera-

tion. In the denominator is the selection coefficient s, which is the proportional

decrease in relative fitness caused by carrying a copy of the mutation.^4

Equation 5.9 carries the simple and intuitive message that a deleterious muta-

tion will be more common if it appears at a higher rate (larger μ) and has weaker

deleterious effects (smaller s). While both numbers vary tremendously among loci

and organisms, to make the ideas clear consider a locus that mutates to a deleterious

allele at a rate of μ = 10–6 per generation, and this allele decreases relative fitness by

s = 0.01. At equilibrium, the deleterious allele will have a frequency of pˆ = 0.0001.

The mutation load

Deleterious mutations decrease survival and/or fecundity, and so they decrease a

population’s mean fitness. Remarkably, the impact on mean fitness of a mutation

is independent of whether the deleterious effect is strong or weak. Equation 5.9

shows that very harmful mutations will only persist at very low frequencies, while

mutations with milder effects will reach equilibrium at higher frequencies. The

net effect is that highly deleterious and weakly deleterious mutations decrease the

population’s mean fitness by the same amount.

The mutation load, represented by L, is the proportion by which the mean fit-

ness of individuals in the population is reduced by deleterious mutations compared

(^4) Equation 5.9 is an approximation that applies when μ << s and the mutation is not completely
recessive, which is typically the case. The fitness of the mutant homozygote does not matter
because it is so rare in this case. A more complex equation applies when those conditions do not
hold (see [18]).
p
μ
ˆ ≈ s
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