Evolution, 4th Edition

92 CHAPTER 4

Effects of mutations

Mutations affect virtually all aspects of an organism, ranging from the ability of

a bacterium to metabolize a new substrate to the ability of a person to learn lan-

guage. Despite the huge range of effects that mutations have, they show two gen-

eral features.

The first is pleiotropy, which occurs when a single mutation affects multiple

traits. An extreme example is a type of dwarfism called achondroplasia (FIGURE

4.16), which results from a mutation in a single gene that interferes with the con-

version of cartilage to bone during development. This decreases the size of many

bones in the body, particularly in the arms and legs. It also decreases longevity and

affects many physiological traits.

Virtually all mutations that have phenotypic effects show pleiotropy. Often the

effects are on seemingly unrelated traits. Pleiotropy therefore plays a key role in

evolution: genetic changes that alter one aspect of an organism invariably have

side effects on other aspects (see Chapters 5 and 6).

Mutation is fundamental to genetics and evolution, and

generations of scientists have devoted their careers to its

study. Several strategies have been invented to estimate

mutation rates [11, 13]. The first approach used was pheno-

type screening. Here the investigator examines (“screens”)

a large number of individuals in a laboratory population,

looking for changes in a character caused by a new muta-

tion (for example, changes in the eye color of the fruit fly

Drosophila melanogaster). The mutation rate, μ, is simply

estimated by counting the number of new mutations

found by the total number of individuals. There are sev-

eral drawbacks of this method; among them, we cannot

estimate mutation rates at individual DNA bases, and only

some kinds of organisms can be used.

Another strategy became possible with the advent

of DNA sequencing. The phylogenetic method exploits

the fact that if a segment of chromosome has no effect

on fitness, it will accumulate mutations at a rate of μ per

generation (as we will see in Chapter 7). Two species that

last shared a common ancestor t generations ago are

therefore expected to differ in that segment by 2μt muta-

tions. (The factor of 2 appears because mutations have

accumulated in each of the two species since their com-

mon ancestor.) By sequencing a neutrally evolving piece

of chromosome in two species, we can count the number

of mutations by which they differ. If we know when their

last common ancestor lived (for example, from fossils) and

the number of generations per year, we can then calculate

μ. Weaknesses of this approach are that it can be applied

only to neutrally evolving regions of the genome, and

requires that we know the number of generations since

the common ancestor.

A related method is called mutation accumulation.

Here several laboratory populations are established from

a single founding population (or individual, in the case

of asexual species). Each population is maintained under

conditions that largely eliminate natural selection so that

mutation is the only evolutionary process at work. After

many generations, individuals from each population are

sequenced, and mutation rate is estimated by the same

calculation used in the phylogenetic method. An ad-

vantage of this approach is that we can be much more

confident about the number of generations since the

common ancestor and the assumption of neutral evolu-

tion. Disadvantages are that there are fewer mutations to

study (because they accumulate over a much shorter time)

and that only some species are suitable.

The conceptually simplest method for estimating muta-

tion rates became possible recently as DNA sequencing

became relatively inexpensive. In the direct method, we

sequence the DNA of parents and offspring and look for

differences caused by mutations. This approach is free

of the assumptions that are important weaknesses of the

other two methods. But it too has limitations. The chance

of a mutation in any specific gene is extremely small, and

so at present the direct method can only give estimates for

mutation rates that are averages over large regions of the

genome.

BOX 4A

Estimating Mutation Rates

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