Essential Cell Biology 5th edition

Mendel and the Laws of Inheritance
673
mutant allele, r, does not. Because they lack this enzyme, plants that
are homozygous for the r allele contain more sugar and less starch than
plants that possess the dominant R allele, which gives their peas a wrinkled
appearance. The sweet peas available in the supermarket are often
wrinkled mutants of the same type that Mendel studied.
Although most loss-of-function mutations are recessive, some can be
dominant. Take, for example, a mutation that causes a protein to misfold.
In a heterozygote, 50% of the proteins produced would be misfolded
and inactive, while the other 50% would function normally. However, the
misfolded form of the protein could go on to form aggregates that cause
severe problems for the cell (see Figure 4−19). Because of its widespread
impact, this particular loss-of-function mutation would be dominant.
Mutations that increase the activity of a gene or its product, or result
in the gene being expressed in inappropriate circumstances, are called
gain-of-function mutations (see Figure 19−30). Such mutations are
usually dominant. For example, as we saw in Chapter 16, certain mutations
in the Ras gene generate a form of the protein that is always active.
Because the normal Ras protein is involved in controlling cell proliferation,
the mutant protein drives cells to multiply inappropriately, even in
the absence of signals that are normally required to stimulate cell division—thereby
promoting the development of cancer. About 30% of all
human cancers contain such dominant, gain-of-function mutations in
the Ras gene.
Each of Us Carries Many Potentially Harmful Recessive
Mutations
As we saw in Chapter 9, mutations that occur in the germ line provide
the fodder for evolution. They can alter the fitness of an organism, making
it either less or more likely for the individual to survive and leave
progeny. Natural selection determines whether these mutations are preserved:
those that confer a selective advantage on an organism tend to
be perpetuated, whereas those that compromise an organism’s fitness or
ability to procreate tend to be lost.
The great majority of chance mutations are either neutral, with no
effect on phenotype, or deleterious. A deleterious mutation that is dominant—one
that exerts its negative effects when present even in a single
copy—will be eliminated almost as soon as it arises. In extreme cases,
if a mutant organism is unable to reproduce, the mutation that causes
that failure will be lost from the population when the mutant individual
dies. For deleterious mutations that are recessive, things are a little more
complicated. When such a mutation first arises, it will generally be present
in only a single copy. The organism that carries the mutation can
produce just as many progeny as other individuals; some of these progeny
will inherit a single copy of the mutation, and they too will appear fit
and healthy. But as they and their descendants begin to mate with one
another, some individuals will inherit two copies of the mutant allele and
display an abnormal phenotype.
If such a homozygous individual fails to reproduce, two copies of the
mutant allele will be lost from the population. Eventually, an equilibrium
is reached, where the rate at which new mutations occur in the gene
balances the rate at which these mutant alleles are lost through matings
that yield abnormal, homozygous mutant individuals. As a consequence,
many deleterious recessive mutations are present in heterozygous
individuals at a surprisingly high frequency, even though homozygous
individuals showing the deleterious phenotype are rare. For example, the
most common form of hereditary deafness (due to mutations in a gene
QUESTION 19–3
Imagine that each chromosome
undergoes one and only one
crossover event on each chromatid
during each meiosis. How would
the co-inheritance of traits that are
determined by genes at opposite
ends of the same chromosome
compare with the co-inheritance
observed for genes on two different
chromosomes? How does this
compare with the actual situation?