# Reciprocal genetics of recently-evolved vertebrate immunity and helminth counter-adaptation

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT STORRS · 2023 · $382,330

## Abstract

PROJECT SUMMARY/ABSTRACT
Vertebrates evolved sophisticated immune systems to eliminate infections by helminth parasites
(tapeworms, nematodes). Nevertheless, helminths often succeed in establishing persistent infections
because they evolved strategies to evade or manipulate their host’s immune system. Because of this host-
parasite co-evolution, infection success is expected to depend on an epistatic interaction between host
immune genes and parasites’ immune-evasion genes. But, the immunogenetic mechanisms underlying
this between-species epistasis remains poorly understood, because most studies focus on immunological
effects of either host genes, or parasite genes, studied separately. Few experimental models of infection are
amenable to ‘reciprocal mapping’ – the concurrent genetic analysis of both interacting species. A small
fish, the threespine stickleback (Gasterosteus aculeatus), and its parasitic tapeworm (Schistocephalus
solidus), offer an experimentally tractable system for reciprocal genetic analysis of trans-
species epistasis between a vertebrate host and cestode parasite. Some natural populations of
stickleback evolved an aggressive inflammatory response to tapeworm infection that limits tapeworm
growth and survival, but results in severe and persistent fibrosis throughout the body cavity, a new model
for human Encapsulating Peritoneal Sclerosis. Although an effective defense against infection, this fibrosis
is also pathological, limiting fish mobility and reproduction. To ameliorate this pathology, some
stickleback populations evolved a remarkable capacity to recover, partially reversing earlier fibrosis. Other
populations evolved a tolerance strategy, allowing tapeworm growth by suppressing fibrosis at the start of
infection; but these genotypes are unable to reverse fibrosis when it does occur. Aim 1 is to identify the
genetic basis of naturally-evolved variation among stickleback populations in the speed of fibrosis onset,
maximum severity, and reversal. We will achieve this using a triangulation approach merging QTL linkage
mapping, population genomics, and experimental evolution. CRISPR/cas9 editing will be used to confirm
the phenotypic effect of mapped genes. However, fibrosis is also a phenotypic outcome of heritable
differences between parasite populations. So, Aim 2 is to identify tapeworm genes that modulate the host
fibrosis response, using QTL mapping, population genomics and experimental gene editing. Aim 3
merges the results of Aims 1&2, to test for between-species epistatic interactions (synergy between host
and parasite genes) regulating onset, severity, and reversal of fibrosis. Ultimately, our goal is to identify
host and parasite genes that jointly determine infection success, and influence fibrosis severity or
suppression, to understand (i) mechanisms of immunity to peritoneal helminth infections, (ii) how the
cestode evolved to suppress or evade host immunity, and (iii) the genes underlying variation in onset,
...

## Key facts

- **NIH application ID:** 10658506
- **Project number:** 2R01AI123659-07
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Daniel Imara Bolnick
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $382,330
- **Award type:** 2
- **Project period:** 2017-07-14 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10658506

## Citation

> US National Institutes of Health, RePORTER application 10658506, Reciprocal genetics of recently-evolved vertebrate immunity and helminth counter-adaptation (2R01AI123659-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10658506. Licensed CC0.

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