# Role of spatial structure in shaping viral population diversity and evolution

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $570,602

## Abstract

Summary
Viral evolution enables the emergence of novel viral pathogens in the human population. The evolution of
influenza A virus is also critical for the maintenance of seasonal lineages in the context of host immunity.
Evolution can result from selection, leading to increased fitness, or stochastic processes that typically decrease
fitness. The relative potency of selective and stochastic forces is therefore a critical determinant of the adaptive
potential of a population. Based on evolutionary theory, we hypothesize that the magnitude of stochastic effects
in viral evolution is strongly impacted by the spatial structure that characterizes viral spread within a host. In
other words, the expansion of a virus population in space may give rise to random, within-host bottlenecks and
founder effects that weaken the efficiency of natural selection. Factors that shape viral spread - including viral
phenotypes, host responses and physical characteristics of the host environment - are therefore predicted to
impact viral genetic diversity and evolution. Our overarching hypothesis is that viral features that modulate
viral spatial structure also modulate viral diversity and evolution. We will test this hypothesis for influenza
A virus using a well-integrated combination of simulation modeling and experimental approaches. In Aim 1, we
will use computational, cell culture and ferret models to examine the consequences of spatially structured spread
for genetic diversity of viral populations. For our experiments, we will use viruses carrying a selectively neutral
barcode to allow robust quantification of viral diversity. In this way, the degree to which stochastic effects
dominate viral dynamics will be examined under a range of conditions. In Aim 2, we will evaluate the
consequences of spatially structured spread for both purifying and positive selection. Computational approaches
will be used to develop hypotheses of how long distance virus dispersal impacts the ability of de novo beneficial
and deleterious mutations to reach dominance. These model predictions will then be tested using experimental
evolution under conditions of common vs. rare long distance dispersal. In this way, we will test the theoretical
concept that stochastic effects associated with spatial structure impede the ability of natural selection to act on
expanding populations. Taken together, the research proposed in these two aims will uncover the importance of
spatial structure to viral population biology and evolution, deepening our fundamental understanding of the forces
shaping viral evolution in nature.

## Key facts

- **NIH application ID:** 10072855
- **Project number:** 1R01AI154894-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Katharina V Koelle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $570,602
- **Award type:** 1
- **Project period:** 2020-08-17 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072855

## Citation

> US National Institutes of Health, RePORTER application 10072855, Role of spatial structure in shaping viral population diversity and evolution (1R01AI154894-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10072855. Licensed CC0.

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