# Co-evolutionary Genetics of Host-Parasite Interactions

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $391,525

## Abstract

ABSTRACT
There is a fundamental gap in our understanding of how host-parasite interactions maintain genetic variation
within species, including humans. Interactions between humans and long-lived eukaryotic parasites may be the
most important agents of natural selection across the human genome and may be responsible for the
maintenance of genome-wide functional variation within humans (balancing selection). However, linking the
agents of balancing selection with their genomic targets remains a major challenge. Continued existence of this
gap is an important problem because until it is filled there is a limited understanding of the mechanisms
responsible for potential maintenance of genetic variation within species. The long-term goal of the investigator's
laboratory is to understand the genetic basis of host-parasite adaptations. The objective over the next five years
is to identify agents and targets of selection arising from host-parasite interactions. The central hypothesis is that
host-parasite interactions maintain genetic variation within species. The rationale is that transitions to parasitism
on the genetic model plant Arabidopsis thaliana has occurred within the genetic model Drosophila lineage,
allowing in-depth study. Guided by strong preliminary data, this hypothesis will be tested by pursuing these two
overarching research questions: 1). Identify molecular genetic changes that underpin the transition to parasitism
in a fly, 2) Determine if host-parasite interactions lead to the maintenance of genome-wide variation in flies and
plants. Under the first question, the genomic architecture underlying the evolutionary transition to parasitism will
be identified in the Drosophilidae. Next-generation sequencing and comparative genomics studies will identify
genes necessary for the evolution parasitism from free living fruit flies. Preliminary studies show that this
approach holds great promise for finding “parasite-genes” and that the approach is feasible in the applicants'
hands. Under the second question, populations of parasitic flies will be evolved with single or mixed host
genotypes that vary in resistance traits. An evolve-and-resequence approach will test if genome-wide variation
is maintained by balancing selection in flies. In the plants, a genome-wide association (GWAS) study approach
will be used to identify loci associated with resistance to flies. The applicants have shown that these approaches
will identify targets of balancing selection. Under both aims, functional studies using in vitro and in vivo
approaches will be used to link evolutionary patterns with functional phenotypes. The proposed research is
significant because it will be the first study in a continuum of research expected to lead to an integrative
understanding of the role that host-parasite interactions play in shaping patterns of genome evolution. There is
promise that general principles will be discovered relating to the role host-parasite interactions play in...

## Key facts

- **NIH application ID:** 9941101
- **Project number:** 5R35GM119816-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** NOAH K WHITEMAN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,525
- **Award type:** 5
- **Project period:** 2016-08-11 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9941101

## Citation

> US National Institutes of Health, RePORTER application 9941101, Co-evolutionary Genetics of Host-Parasite Interactions (5R35GM119816-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9941101. Licensed CC0.

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