Introduction to Our Research
The current efforts of the laboratory are centered on the
use of LINE-1 repetitive sequences as a probe of mammalian
molecular genetics. LINE-1 is a transposon that has left
over 100,000 copies of itself in the genome of mammals.
Through molecular evolutionary reconstruction from this
extensive sequence record, we are attempting to resolve the
following biological issues:
(Background on LINE-1)
-
What controls LINE-1 copy number? LINE-1 is
considered to be a selfish parasite of the genome. Why
doesn't the number of copies
expand until it overwhelms the
host?
LINE-1 has maintained itself stably
in the mammalian genome for over 100,000 years, in spite of
major revisions in the host's genomic mechanics. How did
LINE-1 manage to adapt to the major changes in mutation
pressure exerted against it and the major changes in host
generation time that limit its capacity to spread in the
population. Through a detailed reconstruction of the LINE-1
history, we hope to learn what is the principle that makes
coexistence of host and transposon possible, and eventually
see how that principle is executed by a transposon that only
makes two proteins.
Selfish Transposon Theory
-
Can LINE-1 be used to monitor the rate of processes
affecting the host genome? Once LINE-1 sequences are
dispersed in the genome, they drift within the population
and acquire mutations, recombinations, etc. according to the
same pressures that affect the surrounding mammalian genes.
Since LINE-1 sequences contain a record of their time of
introduction, the frequency of different events that happen
to them over this time can be expressed as a rate. We hope
to use LINE-1 to ascertain genome-wide rates of genetic
drift and gene conversion, two important parameters for
mammalian genetics that are currently beyond reach.
Project Status
-
Can LINE-1 give a definitive measure on the relative
contribution of drift and selective pressure to the
evolution of its proteins? LINE-1 proteins evolve in
sequence over time as do ordinary cellular proteins, except
that the extensive record of LINE-1 sequence will eventually
allow the reconstruction of the exact order of amino acid
changes accepted by functional LINE-1 proteins. The order
of change is important, because the acceptability of a given
side chain at any particular position is influenced by
changes to the identity of its neighbors. The various
theories of protein evolution don't agree on how to handle
this, because of a lack of empirical data upon which to
ground the theory. We hope to fill this void with LINE-1
data.
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