The Molecular Evolution of Proteins and Viruses
Rapid evolution is a defining
feature of many of the most medically problematic viral diseases,
including influenza. Although this rapid evolution is usually bad from
the perspective of public health, it offers a unique vantage from which
to study a range of important questions in biology. For instance,
consider the figure below, which summarizes the evolution of the human
and swine descendants of the 1918 influenza pandemic. It took less than
90 years for these two viral lineages to become as different at the
protein level as humans and pigs themselves – and the full sequences of
many of the evolutionary intermediates are known. Furthermore, this is
just one example of the many viral evolutionary histories that can be
reconstructed in remarkable detail.
We apply a combination of experimental and computational approaches
to use the information in such histories to address questions such as:
- What are the constraints that shape evolutionary trajectories? Can
we use an understanding of these constraints to better predict future
- Can we identify the underlying molecular changes that enable
phenotypically obvious and medically important evolutionary events such
as drug resistance, immune escape, and host-species transfer?
- When a single ancestor gives rise to multiple parallel lines of
descent (such as the human and swine lineages in the figure below), in
what ways are the subsequent molecular changes similar, and how do they
differ? Can we identify selection pressures (such as variation in the
host immune systems) responsible for the differences?
- Why do some viruses (such as influenza) so readily escape
pre-existing immunity, while others with similarly high mutation rates
(such as polio) can easily be tamed by a vaccine? Can we identify
physical properties that contribute to differences in molecular
- How can we create therapeutics and vaccines that are more resistant to viral evolutionary escape?