Omenn Prize awarded to an article by Demogines, et al. that explicates a host-pathogen arms race

The Foundation for Evolution, Medicine, & Public Health announces the winner of the Omenn Prize for the best article published in 2013 on a topic related to evolution in the context of medicine and public health.  The Prize Committee, Allen Rodrigo (chair), Carl Bergstrom, and Sarah Tishkoff, considered 47 articles, and awarded the prize to Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein by Demogines A, Abraham J, Choe H, Farzan M, Sawyer SL (2013). PLoS Biol 11(5):e1001571. doi: 10.1371/journal.pbio.1001571

The first author, Ann Demogines, will receive the $5000 Prize.  She is a Research Associate in the Center for Systems and Synthetic Biology, College of Natural Sciences, University of Texas, Austin, where she works in the laboratory of Sara Sawyer.  The Foundation is grateful to Gilbert Omenn for making this prize possible.

 The Committee cited four other papers for Honorable Mention:

•  Alberts, S. C., Altmann, J., Brockman, D. K., Cords, M., Fedigan, L. M., Pusey, A., … & Bronikowski, A. M. (2013). Reproductive aging patterns in primates reveal that humans are distinct. Proceedings of the National Academy of Sciences, 110(33), 13440-13445.
•  Graves, Christopher J., Vera ID Ros, Brian Stevenson, Paul D. Sniegowski, and Dustin Brisson. “Natural Selection Promotes Antigenic Evolvability.” PLoS pathogens 9, no. 11 (2013): e1003766.
•  Morrow, Edward H., and Tim Connallon. “Implications of sex‐specific selection for the genetic basis of disease.” Evolutionary applications 6, no. 8 (2013): 1208-1217.
•  Huijben, Silvie, Andrew S. Bell, Derek G. Sim, Danielle Tomasello, Nicole Mideo, Troy Day, and Andrew F. Read. “Aggressive Chemotherapy and the Selection of Drug Resistant Pathogens.” PLoS pathogens 9, no. 9 (2013): e1003578.

The Prize Committee’s Award Statement Is below
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Many viruses evolve rapidly in response to host immune surveillance and, in the case of zoonotic transmission, to the new cellular landscapes of different host species.   But how do hosts respond to different viral challenges, especially when the points of viral entry are cell-surface proteins that modulate important functions? The 2013 Omenn Prize-winning paper by Ann Demogines and her co-authors (Demogines et al, 2013, PLoS Biology 11:e1001571) addresses exactly this question. Demogines and colleagues show that the cell-surface Transferrin Receptor (TfR1), which is responsible for moving iron into cells but which is also a gateway to many viruses that cause hemorrhagic fever in rodents and humans, bears the signature of repeated substitutions that reduce the hosts’ vulnerability to viral attack. Importantly, these substitutions do not markedly impede the iron-uptake function of TfR1.  Demogines et al synthesize the results from an exhaustive and diverse array of analyses, including analyses of codon evolution, structural analysis of TfR1 substitutions, phylogenetic reconstruction, and in vitro functional analyses. From this they craft a compelling narrative of the evolutionary patterns and processes in this molecular arms race between virus and host.  They identify naturally occurring variants segregating in humans that influence viral entry into cells in vitro.   Thus, these results also shed light on the evolution of genetic variants that influence human disease risk.  The Omenn Prize committee were impressed with the breadth of their research, and the extent to which it elucidates both proximate and ultimate causes of virus-host variation.

The Omenn Prize committee also singled out four other nominated papers for honorable mention. Alberts et al (2013, PNAS 110:13440) demonstrate that the pattern of reproductive senescence in humans differed from that seen in seven other primate species, with humans spending a substantial portion of their lives after they lose the ability to reproduce.  The committee was impressed with the comprehensive cross-species analysis, and felt that the research exemplified the value of an approach that looked beyond the confines of human biology to answer an important question in human health and well-being. The paper by Graves et al (PLoS Pathogens 9:e1003766) demonstrates how Borrelia burgdorferi, the bacterium that causes Lyme disease, is able to modify its surface antigen VlsE by rearranging paralogous vls cassettes to construct the vlsE gene. Graves et al provide convincing evidence that even unexpressed cassettes accumulate nonsynonymous substitutions, thus increasing the opportunity for the virus to adapt to hosts and to evade immune surveillance.  This phenomenon is directly related to the very topical issue of “evolvability”, and the committee was pleased to see that research on a medically important pathogen provided valuable feedback to evolutionary theory.  Morrow and Connallon (2013, Evolutionary Applications 6: 1208) construct a population genetics model of sex-associated disease-causing traits which predicts that alleles under sex-specific selection, including sexually antagonistic alleles, disproportionally contributed to the incidence of these traits and that  differences in their relative frequencies across the sexes can amplify differences in the genetic predisposition of complex diseases between sexes.  The application of population genetics theory, particularly theory that is based on the dynamics of selection, has a natural and important part to play in our understanding of disease, and the committee saw this paper as an excellent example of this crossover.  Finally, should we treat infections aggressively, as de facto standards dictate, or is there merit in less aggressive treatments?  Huijben et al (2013; PLoS Pathogens 9:e1003578) demonstrate using a rodent malaria model that when drug-resistant variants of the parasite are present, aggressive treatment selects inexorably for the increase in resistant parasites. In contrast, less aggressive treatment reduced the probability of transmission without significantly affecting host outcome.  The committee was excited by this paper because it linked the evolution of a pathogen to possible treatment strategies for some human infections.
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