Seminar: Asher Leeks

Evolutionary conflict in viral populations: Causes, consequences, and clinical predictions

Our lab studies the causes and consequences of evolutionary conflict within viral infections, combining mathematical modelling, bioinformatic analyses of natural infections, and experimental evolution. To successfully replicate inside infected cells, viruses must produce shared gene products, that can be used by multiple viral genomes within the same cell, and hence act as evolutionary public goods. As a result, non-functional mutants called 'cheats' emerge, which are a type of molecular parasite commonly formed by large deletions in public goods genes. Cheats can spread by exploiting public goods encoded by full-length viruses, often gaining large fitness advantages against wildtype viruses, while driving substantial declines in the overall viral population abundance. Cheats exist across the viral universe, arise frequently in laboratory infections, and reflect the emergence of evolutionary conflict at the molecular level.

In this talk, I will start by presenting work that explores the evolutionary consequences of cheats for viral infections, including their potential to drive viral populations extinct over short timescales, or to drive the emergence of new forms of genome organisation over longer timescales. I will then discuss our recent work identifying and quantifying cheats in natural viral infections, using both wildlife surveillance and human clinical datasets. Across >10,000 avian influenza infections, we have found that viral cheats are a major source of within-host viral genetic variability, sometimes outnumber wildtype viruses within infections, and accumulate in a genotype & host-specific manner, indicating that the presence of specific cheat sequences could be used to identify the host-of-origin within environmental samples. In ~200 human influenza infections, we have found that the abundance of viral cheats correlates strongly with clinical infection outcomes, potentially offering a new diagnostic tool, plus insights into individual infection histories. Finally, I will discuss the directions our lab is taking at UBC since we opened in 2025, including evolution-informed BC-wide surveillance efforts for viruses of agricultural systems and livestock, as well as theoretical and experimental work to assess the safety and efficacy of cheats as a novel antiviral therapeutic avenue.