Ancient Virus-like Transposons: from Horizontal Gene Transfer to the Evolution of Novelty

Introduction

From antiparasitic toxins in butterflies to antifreeze proteins in fish, horizontal gene transfer (HGT)—the non-sexual exchange of genes between species—has been observed in all major eukaryotic lineages. However, one of its most fascinating aspects, the transfer mechanism, remains a mystery despite decades of research.

Research Questions

How can DNA leave the donor species, come in close contact with the germline of a second species, and integrate into the genome of its new host? Our lab made a significant breakthrough in our understanding of this process that now allows us to address these questions experimentally.

Discovery of Mavericks

We discovered that Mavericks, ancient eukaryotic transposable elements related to giant viruses and adenoviruses, have mediated the widespread transfer of genes between highly divergent nematode species on a global scale. The gene content of Mavericks suggests that they have a dual lifestyle: both as transposons and as infective enveloped viruses. Yet how they accomplish HGT at the molecular level is unknown.

Objectives of the TOP-GUN Proposal

Having pioneered the identification of the first HGT vector in animals, the objectives of the TOP-GUN proposal are to:

1. Uncover the life cycle of Mavericks and reconstitute Horizontal Gene Transfer in the lab.
2. Dissect the impact of Mavericks and their cargos on molecular innovation and genome evolution.
3. Systemically discover vectors of Horizontal Gene Transfer across eukaryotes in silico.

Methodology

My team and I will pursue these objectives by applying a multidisciplinary approach combining genetics, functional genomics, biochemistry, and structural biology.

Expected Impact

We believe that TOP-GUN will ignite HGT as a new experimental research field and catalyze the development of new payload delivery systems for parasitic nematodes, most of which cannot be genetically modified due to their complex life cycle.