The influence of coevolutionary feedbacks on the origins and maintenance of genetic pleiotropy

Vanderbilt University, Nashville TN

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Abstract

PROJECT SUMMARY/ABSTRACT Pleiotropy, where one gene affects multiple discrete traits, presents an interesting puzzle for evolutionary biologists because mutations that are adaptive for one trait could antagonize the function of another. Recent studies in humans and other organisms have suggested that pleiotropy is extremely common, raising fundamental questions about the function and maintenance of pleiotropy over evolutionary time. There is a long-acknowledged but poorly studied observation that many innate immune signaling pathways in plants, insects, and other taxa also play dual roles in modulating development and other conserved traits. Several studies on genomic signatures of selection have pointed out that pleiotropy constrains the rate of adaptation, which clashes with theoretical and empirical expectations that immune systems need to adapt quickly to counter the rapid evolution of pathogens and parasites. As central questions in my lab evolve around the evolution of immune systems, we want to investigate why pleiotropy is so broadly maintained in immune systems if it could constrain adaptation. My lab will employ several complementary approaches that account for feedbacks across biological scales to study the impact of pleiotropy on host-parasite coevolution. In our first approach, we will integrate genomic data from insect and vertebrate model organisms to investigate selection pressures acting on pleiotropic genes, transcripts, and protein domains and define common features of pleiotropic signaling networks. At the same time, we will build computational models of signaling network evolution to test whether single-sided evolution or coevolution against parasites fundamentally alters the maintenance of pleiotropy in networks. Our third approach will employ experimental evolution to target the deployment of pleiotropic signaling networks during the insect (Tribolium castaneum) host response to manipulative parasites so that we can investigate whether pleiotropy alters coevolutionary outcomes at genotypic and phenotypic levels. The molecular evolution results from the first approach will help us build more realistic networks for the agent-based models, which will then provide salient hypotheses for the experimental evolution outcomes. In turn, the coevolution experiments will provide empirical insight into statistical signatures of selection and model predictions from the first two approaches. Together, these research avenues will provide insight into an array of fundamental questions about the extent of genetic pleiotropy among essential physiological processes, the influence of pleiotropy on coevolutionary dynamics, and the role of immune system architecture in host adaptation to parasite pressure. Gaining greater insight into the evolutionary forces that shape biological systems has important implications for predicting human pathogen evolution, understanding the origins of diseases like autoimmunity and sepsis, and designing therapeutic treatments that minimize side effects.