Why
there is genome instability? – Discovery of sleeping beauty
Transposable elements (TE) are a large family of DNA
elements widely presented in the genome of organism. These elements may not
share the exactly same sequence, but consist of elements that confer similar
biological function, which is inserting into genome and causing target site duplications.
There are two classes of TE in eukaryotic cells: retrotransposon elements and
DNA transposons.
The first transposon, founded by Barbara McClintock in 1983,
is a naughty gene jumping around in the genome of maize. She found that there
were deletions and insertions in the genome that are related to the change in
the color of corn kernels. This transposon belongs to class II TEs, being
called as DNA copy & paste system (or ctrl+x & ctrl+v system, geeky
joke). Class II transposons are composed of two inverted repeats (IR) at each
end, and one transposase element in the middle, which determines the autonomy
of the transposon. The structure enables class II transposons to insert in the
genome, changing the size of the genome and leading to genome instability.
Class I transposon is a family of retroviral genome (I have
talked about retrotransposon and viral oncology in a previous post). It is
interesting to know that not only in retrovirus, in yeast cells there are
transposons that resemble retrotransposon structure. Ty element includes TyA, a
gag-like protein and TyB, homology to RTase. The structure of Ty element is
shown as follows.
Indication of evolution
Comparing these transposons from different branches of
species reveal the role of transposon in organism development and evolution.
Because the unstable nature of TE leads to mutagenesis, changes in genome sizes
and eventually deleterious mutations, most biologists regard these TEs as
“selfish DNA parasites”. Therefore, selection force is “giving a harsh time” to
the TEs. Many organisms have their special mechanism to inhibit the activity of
TE. In human genome, most of the transposable elements have been inactivated by
mutagenesis long time ago. Very few transposons still remain their function of
being a troublemaker. For example, Alu element is a most common transposon in
human and has been proved to have association with inherited diseases and
cancer. The figure below shows the karyotype of human chromosome of a female
(XX). Green color labels the hybridized Alu element widely distributed in the
chromosomes.
The discovery of TE also shed light on the speciation of
organism in a molecular level. Scientists claim that these TEs have a common
ancestor, and that transposons help exchange genetic information in the
horizontal gene transmission. However, some researchers believe that these TEs
emerged independently in multiple times. But still, except for the understanding
of retroviral genome integration into host genome, we are unable to tell how
the transposon from one ancestral species has been introduced to another
species.
The wake up of sleeping beauty
TEs are named as sleeping beauty by their inactivated nature.
However, in 1997 Ivics et al successfully woke up the sleeping beauty in
salmonid cells. The researchers used a powerful approach to construct an
activated transposon in fish cells by mutagenesis. They mapped several
inactivated mutation in the ORF of sleeping beauty, replaced these mutations
with robust amino acid residues, and finally woke up the beauty. The following
shows how they performed this elegant biological trial.
Reference
Ivics, Z., Hackett, P. B., Plasterk, R. H., & Izsvák, Z.
(1997). Molecular Reconstruction of< i> Sleeping Beauty</i>, a<
i> Tc1</i>-like Transposon from Fish, and Its Transposition in Human
Cells. Cell, 91(4), 501-510.
http://en.wikipedia.org/wiki/Transposable_element
No comments:
Post a Comment