Distinguishability of Episodic Fitness Shifts from Changes in Effective Population

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The evolutionary process is influenced by many factors. However, not all forces of interest are guaranteed to be identifiable from comparative sequence data alone. Here we study what factors shape the distinguishability of changes in the underlying fitness landscape from variation in effective population size over time, since each of these processes can have similar influences on the expected distribution of codon states at affected positions. Using a family of Markov- modulated mutation selection codon models with an explicit population genetics basis, we study distinguishability in terms of the Kullback-Leibler divergence between evolutionary models, and extend this study using simulation. We thereby establish bounds on the number of sequence samples required before and after both fitness shifts and population size shifts on a large phylogenetic tree to achieve acceptable (best case) distinguishability and high power in resultant hypothesis tests. Our results highlight some of the challenges of modelling and inference of non-equilibrium molecular evolutionary processes from finite data.