RT Journal Article
SR Electronic
T1 The impact of purifying and background selection on the inference of population history: problems and prospects
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.28.066365
DO 10.1101/2020.04.28.066365
A1 Parul Johri
A1 Kellen Riall
A1 Hannes Becher
A1 Brian Charlesworth
A1 Jeffrey D. Jensen
YR 2020
UL http://biorxiv.org/content/early/2020/07/06/2020.04.28.066365.abstract
AB Current procedures for inferring population history are generally performed under the assumption of complete neutrality - that is, by neglecting both direct selection and the effects of selection on linked sites. We here examine how the presence of direct purifying and background selection may bias demographic inference by evaluating two commonly-used methods (MSMC and fastsimcoal2), specifically studying how the underlying shape of the distribution of fitness effects (DFE) and the fraction of directly selected sites interact with demographic parameter estimation. The results show that, even after masking functional genomic regions, background selection effects may result in the mis-inference of population growth under models of both constant population size as well as decline. This effect is amplified as the strength of purifying selection and the density of directly selected sites increases, as indicated by the distortion of the site frequency spectrum and levels of nucleotide diversity at linked neutral sites. We also show how simulated changes in background selection effects caused by population size changes can be predicted analytically. We propose a potential method for correcting for the mis-inference of population growth caused by selection. By treating the DFE as a nuisance parameter and averaging across all potential realizations, we demonstrate that even directly selected sites may be used to infer demographic histories with reasonable accuracy.Competing Interest StatementThe authors have declared no competing interest.