Shrinkage-based random local clocks with scalable inference.

Local clock models propose that the rate of molecular evolution is constant within phylogenetic sub-trees. Current local clock inference procedures scale poorly to large taxa problems, impose model misspecification, or require a priori knowledge of the existence and location of clocks. To overcome these challenges, we present an autocorrelated, Bayesian model of heritable clock rate evolution that leverages heavy-tailed priors with mean zero to shrink increments of change between branch-specific clocks. We further develop an efficient Hamiltonian Monte Carlo sampler that exploits closed form gradient computations to scale our model to large trees. Inference under our shrinkage-clock exhibits an over 3-fold speed increase compared to the popular random local clock when estimating branch-specific clock rates on a simulated dataset. We further show our shrinkage-clock recovers known local clocks within a rodent and mammalian phylogeny. Finally, in a problem that once appeared computationally impractical, we investigate the heritable clock structure of various surface glycoproteins of influenza A virus in the absence of prior knowledge about clock placement.