Experimental evolution of emerging viruses To infect a novel host, viruses usually need to evolve. Most viruses require a host range mutation to enter a novel host. Once able to enter, they fix additional mutations to adapt to the novel host, and to increase their transmission between hosts. While the exact mutations that are beneficial for a particular virus on a particular host are highly individual and dependent on the virus’ ecology, there may be general properties of adaptive mutations in emerging viruses that we can study in model systems. For instance, RNA viruses seem much more likely than DNA viruses to host-shift into humans -- is this because host range mutations have a lower cost in RNA viruses? Or is it because RNA viruses have higher mutation rates, and therefore more frequently sample host range mutations? Is it simply because there are many RNA viruses infecting other mammals, and it is easier for viruses to host-shift between closely related hosts?
We use experimental evolution to simulate viral emergence events on novel hosts. This allows us to study the frequency and effects of adaptive mutations in a wide variety of viruses (RNA and DNA, single- and double-stranded, segmented and monopartite). Longer evolution experiments also allow us to study the adaptive walks of these viruses as they adapt to the novel host.
Understanding viral genetic variation
As natural selection can only act on variation within a population, we also study the mechanisms by which viruses create and maintain variation: mutation, recombination, reassortment. This work spans the gamut from field work to molecular microbial genetics, and often relies on intensive sequencing of viral populations. Currently, we are focused on understanding the forces shaping the diversity in natural populations of geminiviruses, which are frequently emerging pathogens of plants.
Our wet lab work uses a number of bacteriophage systems, such as the highly unusual phage phi6, and the ssDNA phage phiX174. We also work on/collaborate with labs that work on circular ssDNA viruses of plants and animals (anelloviruses, geminiviruses, circoviruses, nanoviruses.).
Photo: Yale, phage stencil plate prepared by David Kysela
What is the downside to having a host range mutation?
We obtained nine different, spontaneous host range mutations of the dsRNA phage phi6, each due to a single point mutation in the host attachment gene P3. These viruses which had a beneficial mutation -- one that expanded its host range so it could exploit a greater number of hosts -- usually suffered a cost in fitness on the original host of the virus, relative to the unmutated ancestor (dashed line). The data shown are average fitness measures with 95% confidence intervals (Duffy et al. 2006). The colors distinguish different expanded host ranges.
