# The causes of balancing selection on immunity genes: from populations to molecular interactions.

> **NIH NIH R01** · UNIVERSITY OF KANSAS LAWRENCE · 2021 · $363,937

## Abstract

Project Summary
Immunity is an enormously important topic for human health with economic costs of infectious disease
eclipsing $100 billion in 2014. At the same time, the evolution of the immune system is fertile ground for the
study of evolutionary processes because a) natural selection on immunity is intense since the outcome of
infection is often life or death and b) pathogens have the ability to respond to host adaptation leading to rapid
evolution through an evolutionary arms race. Since insects lack an adaptive immune system, they are excellent
models to understand the molecular genetics and evolution of innate immunity. An important component of
innate immunity is the complement of antimicrobial peptides (AMPs) that are produced and secreted by host
cells upon infection and directly inhibit pathogens. Variation in the genes encoding these AMPs is often
maintained by balancing selection, the process by which multiple alleles are maintained at the same locus
through various mechanisms. While instances of balancing selection are being reported more and more
frequently, we lack a comprehensive understanding of the mechanistic basis of balancing selection in most
examples. The ability to connect broad scale patterns of DNA sequence diversity to mechanistic differences in
protein function is innovative and would provide a comprehensive view of balancing selection. Furthermore, the
identification of particular amino acid polymorphisms that are maintained by balancing selection facilitates the
mechanistic study of balancing selection because the presumptive causative mutations are known a priori. Our
use of Drosophila as a model system also allows for study of AMP variation in vivo in a way that is much more
cost effective than several other model systems, while allowing the flexibility to move between in vitro and
whole organism in vivo study. These peptides are ideal for the functional study of balancing selection because
a) genetic variation in several peptides is maintained by balancing selection, providing replication, b) AMPs are
effectors and thus interact directly with pathogens and c) AMPs are small and can be easily studied in vitro.
Aim 1 involves determining peptide differences in vitro to understand how single amino acid changes lead to
different function. Aim 2 will determine the effect of AMP variation on the entire organism and investigate the
role of life history tradeoffs in balancing selection. The project is significant because it will provide a deeper
understanding of evolutionary processes by uncovering molecular mechanisms and may provide a better
understanding of innate immunity to enhance our treatment of human disease.

## Key facts

- **NIH application ID:** 10143182
- **Project number:** 5R01AI139154-04
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **Principal Investigator:** Robert L Unckless
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $363,937
- **Award type:** 5
- **Project period:** 2018-05-17 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143182

## Citation

> US National Institutes of Health, RePORTER application 10143182, The causes of balancing selection on immunity genes: from populations to molecular interactions. (5R01AI139154-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10143182. Licensed CC0.

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