Essential Cell Biology 5th edition

316 CHAPTER 9 How Genes and Genomes Evolve
Figure 9−24 The most common mobile
genetic elements in bacteria, DNAonly
transposons, move by two types
of mechanism. (A) In cut-and-paste
transposition, the element is cut out of the
donor DNA and inserted into the target
DNA, leaving behind a broken donor
DNA molecule, which is subsequently
repaired. (B) In replicative transposition, the
mobile genetic element is copied by DNA
replication. The donor molecule remains
unchanged, and the target molecule
receives a copy of the mobile genetic
element. In general, a particular type of
transposon moves by only one of these
mechanisms. However, the two mechanisms
have many enzymatic similarities, and a few
transposons can move by either mechanism.
The donor and target DNAs can be part
of the same DNA molecule or reside on
different DNA molecules.
QUESTION 9–4
Many transposons move within a
genome by replicative mechanisms
(such as those shown in Figure
9−24B). They therefore increase
in copy number each time they
transpose. Although individual
transposition events are rare, many
transposons are found in multiple
copies in genomes. What do you
suppose keeps the transposons
from completely overrunning their
hosts’ genomes?
(A)
(B)
donor DNA
transposon
+
+
target DNA
CUT-AND-PASTE
TRANSPOSITION
REPLICATIVE
TRANSPOSITION
new DNA
sequence
new DNA
sequence
In addition to relocating themselves, mobile genetic elements occasionally
rearrange the DNA sequences of the genome in which they are
embedded. For example, if two mobile genetic elements that are recognized
by the same transposase integrate into neighboring regions
of the same chromosome, ECB5 the DNA e9.24/9.24 between them can be accidentally
excised and inserted into a different gene or chromosome (Figure 9−26).
In eukaryotic genomes, such accidental transposition provides a pathway
for generating novel genes, both by altering gene expression and by
duplicating existing genes.
The Human Genome Contains Two Major Families of
Transposable Sequences
The sequencing of human genomes has revealed many surprises, as we
describe in detail in the next section. But one of the most stunning was
the finding that a large part of our DNA is not entirely our own. Nearly
half of the human genome is made up of mobile genetic elements, which
number in the millions. Some of these elements have moved from place
to place within the human genome using the cut-and-paste mechanism
discussed earlier (see Figure 9−24A). However, most have moved not as
DNA, but via an RNA intermediate. These retrotransposons appear to be
unique to eukaryotes.
One abundant human retrotransposon, the L1 element (sometimes
referred to as LINE-1, a long interspersed nuclear element), is transcribed
into RNA by a host cell’s RNA polymerase. A double-stranded DNA copy
of this RNA is then made using an enzyme called reverse transcriptase,
an unusual DNA polymerase that can use RNA as a template. The reverse
transcriptase is encoded by the L1 element itself. The DNA copy of
the element is then free to reintegrate into another site in the genome
(Figure 9−27).
L1 elements constitute about 15% of the human genome. Although
most copies have been immobilized by the accumulation of deleterious
+
+
IS3
Tn3
transposase gene
transposase gene
~2000
nucleotide pairs
AmpR
Figure 9−25 Transposons contain the components they need
for transposition. Shown here are two types of bacterial DNA-only
transposons. Each carries a gene that encodes a transposase (blue and
red )—the enzyme that catalyzes the element’s movement—as well as
DNA sequences (red) that are recognized by each transposase.
Some transposons carry additional genes (yellow) that encode
enzymes that inactivate antibiotics such as ampicillin (AmpR). The
spread of these transposons is a serious problem in medicine, as it
has allowed many disease-causing bacteria to become resistant to
antibiotics developed during the twentieth century.