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 viral evolution?
- 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 evolvability?
- How can we create therapeutics and vaccines that are more resistant to viral evolutionary escape?
Below are a few selected publications that illustrate some of the approaches that we employ.
Click here for a complete list.
L. Ian Gong, Marc A. Suchard, Jesse D. Bloom. "Stability-mediated epistasis constrains the evolution of an influenza protein." eLife. 2:e00631 (2013) Link
Jesse D. Bloom, L. Ian Gong, and David Baltimore. “Permissive secondary mutations enable the evolution of influenza oseltamivir resistance.” Science. 5983:1272-1275 (2010) Link
Jesse D. Bloom and Matthew J. Glassman. “Inferring stabilizing mutations from protein phylogenies: application to influenza hemagglutinin.” PLoS Comput. Biol. 5:e1000349 (2009) Link
Jesse D. Bloom, Alpan Raval, and Claus O. Wilke. “Thermodynamics of neutral protein evolution.” Genetics. 175:255-266 (2007) Link
