Abstract
AbstractNatural populations are virtually never observed in equilibrium, yet equilibrium approximations comprise the majority of our understanding of population genetics. Using standard tools from statistical physics, a formalism is presented that re-expresses the stochastic equations describing allelic evolution as a partition functional over all possible allelic trajectories (‘paths’) governed by selection, mutation, and drift. A perturbative field theory is developed for strong additive selection, relevant to disease variation, that facilitates the straightforward computation of closed-form approximations for time-dependent moments of the allele frequency distribution across a wide range of non-equilibrium scenarios; examples are presented for constant population size, exponential growth, bottlenecks, and oscillatory size, all of which align well to simulations and break down just above the drift barrier. Equilibration times are computed and, even for static population size, generically extend beyond the order 1/stimescale associated with exponential frequency decay. Though the mutation load is largely robust to variable population size, perturbative drift-based corrections to the deterministic trajectory are readily computed. Under strong selection, the variance of a new mutation’s frequency (related to homozygosity) is dominated by drift-driven dynamics and a transient increase in variance often occurs prior to equilibrating. The excess kurtosis over skew squared is roughly constant (i.e., independent of selection, provided 2Ns≳ 5) for static population size, and thus potentially sensitive to deviation from equilibrium. These insights highlight the value of such closed-form approximations, naturally generated from Feynman diagrams in a perturbative field theory, which can simply and accurately capture the parameter dependences describing a variety of non-equilibrium population genetic phenomena of interest.
Publisher
Cold Spring Harbor Laboratory