# The coevolutionary dynamics of pleiotropic genetic architecture

> **NIH NIH R35** · VANDERBILT UNIVERSITY · 2021 · $395,796

## Abstract

PROJECT SUMMARY/ABSTRACT
The coevolution of hosts and parasites is mediated by genetic mutations that allow one side to gain an advantage over the
other. As the host immune system bears the primary burden of responding to evolving parasites, it is expected to adapt or
diversify in response to natural selection. However, recent population genetics analyses from a variety of animal taxa only
partially bear out this hypothesis, revealing a paucity of adaptive evolution among innate immune gene repertoires relative
to expectations. My recent work suggests that an appreciable proportion of genes associated with innate immune
responses in taxa as broad as humans, insects and plants are pleiotropic, meaning that they also play unrelated roles in
other organismal traits like development and the response to abiotic stress. This observation raises the possibility of
temporal and evolutionary tension between the use of a gene product for developmental and immunological functions.
Current coevolutionary theory largely fails to account for sources of genetic constraint on host defenses, impeding the
translation of existing coevolutionary models into predictions for evolutionary dynamics at the molecular or system level.
Moving forward, a major focus of research in my lab will be to explore the role of pleiotropic genetic architecture on the
evolvability of host immune systems in response to parasite pressure.
To tackle this long-term objective, my lab will employ several complementary approaches. Using transcriptome data, we
will define the extent and dynamics of pleiotropy among developmental, stress, and immunological pathway genes in a
variety of insect model species. We will perform genome-wide evolutionary genetics analyses in these insect species to
quantify signatures of selection on pleiotropic and non-pleiotropic developmental, immunological, and stress response
gene sets relative to null expectations. We will build mathematical models of immune pathway protein networks
possessing different properties – modularity, redundancy, complexity, pleiotropy – and allow them to co-evolve with
parasites, quantifying changes in fitness landscapes to better understand network structures that constrain or promote host
adaptation. In parallel, we will run coevolution experiments using the flour beetle Tribolium castaneum and its natural
parasites. We will manipulate the strength of pleiotropic antagonism among immunity and other processes in these
experiments by limiting host-microbe interactions to a particular developmental stage or altering abiotic stress conditions,
and then compare the evolutionary trajectories and genetic bases of host-microbe interaction outcomes.
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 para...

## Key facts

- **NIH application ID:** 10200098
- **Project number:** 5R35GM138007-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Ann Thomas Tate
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $395,796
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200098

## Citation

> US National Institutes of Health, RePORTER application 10200098, The coevolutionary dynamics of pleiotropic genetic architecture (5R35GM138007-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10200098. Licensed CC0.

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