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High juvenile susceptibility drives infectious disease epidemics across kingdoms, yet the evolutionary mechanisms that maintain this susceptibility are unclear. We tested the hypothesis that juvenile susceptibility is maintained by high costs of resistance by quantifying the genetic correlation between host fitness and age-specific innate resistance to a fungal pathogen in a wild plant. We separately measured the resistance of 45 genetic families of the wild plant,Silene latifolia,to its endemic fungal pathogen,Microbotryum lychnidis-dioicae,at four ages in a controlled inoculation experiment. We then grew these same families in a field common garden and tracked survival and fecundity over a 2-y period and quantified the correlation between age-specific resistance and fitness in the field. We found significant fitness costs associated with disease resistance at juvenile but not at adult host stages. We then used an age-structured compartmental model to show that the magnitude of these costs is sufficient to prevent the evolution of higher juvenile resistance in models, allowing the disease to persist. Taken together, our results show that costs of resistance vary across host lifespan, providing an evolutionary explanation for the maintenance of juvenile susceptibility.
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This content will become publicly available on December 1, 2025
Evolution of STAT2 resistance to flavivirus NS5 occurred multiple times despite genetic constraints
Abstract Zika and dengue virus nonstructural protein 5 antagonism of STAT2, a critical interferon signaling transcription factor, to suppress the host interferon response is required for viremia and pathogenesis in a vertebrate host. This affects viral species tropism, as mouse STAT2 resistance renders only immunocompromised or humanized STAT2 mice infectable. Here, we explore how STAT2 evolution impacts antagonism. By measuring the susceptibility of 38 diverse STAT2 proteins, we demonstrate that resistance arose numerous times in mammalian evolution. In four species, resistance requires distinct sets of multiple amino acid changes that often individually disrupt STAT2 signaling. This reflects an evolutionary ridge where progressive resistance is balanced by the need to maintain STAT2 function. Furthermore, resistance may come with a fitness cost, as resistance that arose early in lemur evolution was subsequently lost in some lemur lineages. These findings underscore that while it is possible to evolve resistance to antagonism, complex evolutionary trajectories are required to avoid detrimental host fitness consequences.
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- Award ID(s):
- 2314898
- PAR ID:
- 10529597
- Publisher / Repository:
- Nature Communications
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 15
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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