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Branch-specific diversification inference
Population genetics of rapid adaptation and fitness inference from trees
Many large microbial populations are genetically diverse and consist of many strains that compete against each other. Competition for susceptible humans, for example, drives the immune escape dynamics of seasonal influenza viruses. I will discuss how such competitive non-neutral dynamics differ from typical population genetic models based on the Kingman coalescent. If many small effect mutation contribute to fitness variation in the population, the evolutionary dynamics converges towards a different universal coalescent process known as the Bolthausen-Sznitman coalescent which generates distinctly different tree ensembles and diversity patters. I will then show how these insights into the population genetics of rapid adaptation can be used to infer relative fitness of individuals in a population from sequence data sampled at a single time point.
Coupling adaptive molecular evolution to phylodynamics using fitness-dependent birth-death models
Beneficial and deleterious mutations cause the fitness of lineages to vary across a phylogeny and thereby shape its branching structure. While standard phylogenetic models do not allow non-neutral mutations to feedback and shape trees, birth-death models can account for this feedback by letting the fitness of lineages depend on their type. To date however, these multi-type birth-death models have only been applied to cases where a lineage's fitness is determined by a single evolving character state. We extend these models to track the fitness of a lineage and sequence evolution at multiple sites. This approach remains computationally tractable by tracking the fitness and ancestral genotype of lineages probabilistically in an approximate manner. Although approximate, we show that we can accurately estimate the fitness of lineages and even specific mutation effects from phylogenies. We apply this approach to estimate the population-level fitness effects of mutations previously identified to modulate the fitness of Ebola virus and human influenza viruses in the lab.
Population genetics of adaptation and ecological diversification on substitutable resources
Most mutations are subject to competitive exclusion, and will either come to dominate a population or go extinct. In special cases, a mutant may evade competitive exclusion by exploiting a different ecological niche. Both types of mutations can be found in large microbial populations, yet little is known about how they combine to determine the genealogical structure of a population. In this talk, I will describe some recent theoretical efforts to address this question, focusing on the dynamics that emerge in simple resource competition models. I’ll show how the competition between ecological diversification and fitness evolution leads to an emergent state of diversification-selection balance, in which semi-stable ecotypes are continuously generated and purged by natural selection. The ecological and genealogical structure of this non-equilibrium steady-state can be characterized analytically in simple asymptotic limits, revealing a crucial dependence on the range of genetically accessible phenotypes. I’ll conclude by discussing potential connections to empirical data, both from laboratory evolution experiments and natural populations of bacteria.