CRePE Project 1:
Predictability of
Viral Evolution
Evolution of many viruses is so rapid
that they can quickly adapt to new hosts
or evolve resistance that renders
antiviral drugs ineffective. Large
population size, high mutation rate, and
relatively small genome size facilitate
rapid and extensive exploration of the
local adaptive landscape. It has
generally been assumed that evolution
has too many degrees of freedom to allow
predicting the molecular bases of such
changes. However, the molecular changes
leading to short-term viral evolution
may be predictable when there are
limited alternative solutions to an
adaptive challenge, or when population
size and mutation rate allow the virus
to quickly find the best of many
possible solutions. ‘Predictability’ may
take the form of general principles,
statistical predictions about changes in
response to specific adaptive
challenges, or definitions of conditions
under which evolution is predictable or
not. Thus, predictability will give
rise to a set of rules of molecular
evolution, and we are now well
positioned to learn these rules. While
it is easy to learn the rules for a
specific virus evolving under a defined
set of conditions, it is more
challenging to determine the generality
of these rules. This project uses a
bacteriophage model system to begin to
address questions about the generality
of rules of viral evolution.
The
specific aims are:
-
To look for signatures of
specific evolutionary processes, such as
recombination, deletions and insertions,
and adaptive substitutions, in the
genomes of natural viral isolates;
-
To
use experimental evolution to develop a
predictive model of the specific
molecular changes that confer gain or
loss of host specificity;
-
To assess
the impact of the spatial population
structure on the trajectory of evolution
using coordinated experimental and
mathematical models;
-
To test our
ability to accurately reconstruct
short-term viral phylogenies using known
phylogenies evolved under conditions of
large population size, high mutation
rate and strong selection.
Information
from natural isolates will be used to
refine our hypothesis about the specific
molecular changes involved in host
specificity. Experimental evolution
will be carried out in chemostats or on
plates, and adapted genomes will be
sequenced. These experiments will test
both the validity and the generality of
the hypothesis. A better understanding
of the rules of molecular evolution
could ultimately help us track
pathogens, anticipate and control
mechanisms of resistance, and develop
long-lasting vaccines and drugs.
Contact:
Dr.
Holly Wichman (Biological
Sciences)
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