# Coevolutionary Dynamics and Gene Exchange Between Nucleo-Cytoplasmic Large DNA Viruses and Eukaryotes

> **NIH NIH R35** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2024 · $369,540

## Abstract

Project Summary
Nucleo-Cytoplasmic Large DNA Viruses (NCLDVs) are a group of eukaryotic pathogens that includes the largest
and most complex viruses known. This group encompasses well-studied families that infect vertebrates, such
as Poxviridae, Asfarviridae, and Iridoviridae, as well as families that infect diverse unicellular eukaryotes, such
as Mimiviridae, Phycodnaviridae, and Marseilleviridae. NCLDVs are an ancient lineage that have co-evolved
with eukaryotes for many millions of years, and the genomes of both viruses and their hosts contain myriad
signatures of past and present interactions. NCLDV genomes encode an impressive complement of host-derived
genes ─ often referred to as viral mimicry genes ─ that are involved in numerous processes such as
immunoregulation, apoptosis inhibition, central carbon metabolism, cytoskeletal structure, nutrient transport, and
translation. The evolutionary history of most of these genes is unclear beyond their original acquisition from
cellular lineages, and the processes that give rise to mimicry are therefore largely unknown. Eukaryotic genomes
also bear testament to their interactions with these viruses, and recent work has shown that endogenized
NCLDVs are surprisingly common across a wide range of eukaryotic hosts, including animals and plants. These
endogenous viral elements range from large >1 Mbp loci ─ termed Giant Endogenous Viral Elements, or GEVEs
─ to smaller loci containing only a few genes that can be traced back to NCLDV. My group has identified GEVEs
across a range of green algae, and I have preliminary data demonstrating that recently-endogenized NCLDVs
are present in the genomes of several strains of the model green alga Chlamydomonas reinhardtii. These and
other recent findings demonstrate that both historical and contemporary gene exchange between NCLDVs and
eukaryotes plays a large role in the genome evolution of both groups, but we currently lack a quantitative
framework or model system for evaluating the nature and extent of these dynamics. Here I propose several
computational and wet-lab research directions aimed at evaluating the evolutionary dynamics of both host-
derived mimicry genes in NCLDVs as well as the NCLDV-derived loci in eukaryotic genomes. I also propose to
develop C. reinhardtii as a model to facilitate in-depth experimental analysis of host-virus interactions and
evaluate the consequences of NCLDV endogenization in detail. Due to the existing genetic tools that have been
developed for C. reinhardtii, establishment of this alga as a new model for NCLDV-host interactions would be a
transformative advance that would enable detailed experimental analyses that are currently not possible in other
virus-host experimental systems. Overall, these research themes form the basis of an interdisciplinary research
program focused on disentangling the evolutionary and molecular dynamics of NCLDV-host interactions. This
work will establish a quantitative framework for understandin...

## Key facts

- **NIH application ID:** 10893452
- **Project number:** 5R35GM147290-03
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Frank O'Neill Aylward
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $369,540
- **Award type:** 5
- **Project period:** 2022-08-16 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893452

## Citation

> US National Institutes of Health, RePORTER application 10893452, Coevolutionary Dynamics and Gene Exchange Between Nucleo-Cytoplasmic Large DNA Viruses and Eukaryotes (5R35GM147290-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10893452. Licensed CC0.

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