%0 Journal Article %A Berit Lindum Waltoft %A Asger Hobolth %T Non-parametric estimation of population size changes from the site frequency spectrum %D 2017 %R 10.1101/125351 %J bioRxiv %P 125351 %X The variability in population size is a key quantity for understanding the evolutionary history of a species. We present a new method, CubSFS, for estimating the changes in population size of a panmictic population from the site frequency spectrum. First, we provide a straightforward proof for the expression of the expected site frequency spectrum depending only on the population size. Our derivation is based on an eigenvalue decomposition of the instantaneous coalescent rate matrix. Second, we solve the inverse problem of determining the variability in population size from an observed SFS. Our solution is based on a cubic spline for the population size. The cubic spline is determined by minimizing the weighted average of two terms, namely (i) the goodness of fit to the SFS, and (ii) a penalty term based on the smoothness of the changes. The weight is determined by cross-validation. The new method is validated on simulated demographic histories and applied on data from nine different human populations. %U https://www.biorxiv.org/content/biorxiv/early/2017/04/07/125351.full.pdf