Page 62 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

7.1 Mutations: Primary Tools of Genetic Analysis 221

Figure 7.2 Point mutations classified by their effect function or change the DNA between genes. We discuss
on DNA. mutations without observable phenotypic consequences in
Starting sequence Chapter 11; such mutations are invaluable for mapping
T C T C G C A T G G T A G G T genes and tracking differences between individuals. In the
A G A G C G T A C C A T C C A remainder of this chapter, we focus on those mutations that
Type of mutation and e ect on base sequence have an impact on gene function and thereby influence
phenotype.
(a) Substitution
Transition: Purine for purine, pyrimidine for pyrimidine
T C T C G C A T A G T A G G T Spontaneous Mutations Occur
A G A G C G T A T C A T C C A
Transversion: Purine for pyrimidine, pyrimidine for purine at a Very Low Rate
T C A C G C A T C G T A G G T Mutations that modify gene function happen so infrequently
A G T G C G T A G C A T C C A
or that geneticists must examine a very large number of indi-
T C T C G C A T T G T A G G T viduals from a formerly homogeneous population to detect
A G A G C G T A A C A T C C A the new phenotypes that reflect these mutations. In one
ongoing study, dedicated investigators have monitored the
(b) Deletion T C T C T G G T A G G T coat colors of millions of specially bred mice and discovered
A G A G A C C A T C C A that on average, a given gene mutates to a recessive allele
in roughly 11 out of every 1 million gametes (Fig. 7.3).
G C A
C G T Studies of several other multicellular, eukaryotic organ-
isms have yielded similar results: an average spontaneous
(c) Insertion A A rate of 2−12 × 10 mutations per gene per gamete.
−6
T T
Looking at the mutation rate from a different perspec-
T C T C AA G C A T G G T A G G T tive, you could ask how many mutations might exist in the
A G A G TT C G T A C C A T C C A

Figure 7.3 Rates of spontaneous mutation. (a) Wild-type
(left) and mutant mouse coat colors: albino (middle), and brown
(C or T) replaces the other; and transversions, in which a (right). (b) Mutation rates from wild type to recessive mutant alleles
purine changes to a pyrimidine, or vice versa. for five coat color genes. Mice from highly inbred wild-type strains
Other types of mutations rearrange DNA sequences were mated with homozygotes for recessive coat color alleles.
rather than just change the identity of a base pair. A deletion Progeny with mutant coat colors indicated the presence of
recessive mutations in gametes produced by the inbred mice.
occurs when a block of one or more nucleotide pairs is lost a (left): © imageBROKER/SuperStock RF; (middle, right): © Charles River
from a DNA molecule; an insertion is just the reverse—the Laboratories
addition of one or more nucleotide pairs (Figs. 7.2b and c). (a)
Deletions and insertions can be as small as a single base
pair or as large as megabases (that is, millions of base pairs).
Large deletions and insertions are only some of the com-
plex mutations that can reorganize genomes by changing
either the order of genes along a chromosome, the number
of genes in the genome, or even the number of chromo-
somes in an organism. We discuss all such chromosomal
rearrangements, which affect many genes at a time, in (b)
Chapter 13. Here, we focus on point mutations (transi-
tions, transversions, and small deletions or insertions) that Number of Number of Mutation
affect one or just a few base pairs in the DNA and thus alter Locus a gametes tested mutations rate ( 10 )
–6
only one gene at a time.
Only a small fraction of the mutations in a genome – 67,395 3 44.5
actually alter the nucleotide sequences of genes in a way a (albino) 919,699 3 3.3
–
b (brown)
–
that affects gene function. By changing one allele to an- c (nonagouti) 150,391 5 33.2
–
other, these mutations modify the structure or amount of a d (dilute) 839,447 10 4 11.9
16.4
243,444
–
ln (leaden)
gene’s protein product, and the modification in protein 2,220,376 25 11.2 (average)
structure or amount can influence phenotype. Other
mutations either alter genes in ways that do not affect their a Mutation is from wild type to the recessive allele shown.