The impact of purifying and background selection on the inference of population history: problems and prospects [article]

Parul Johri, Kellen Riall, Jeffrey D. Jensen
2020 biorxiv/medrxiv  
Current procedures for inferring population history are generally performed under the assumption of complete neutrality - that is, neglecting both direct selection and the effects of selection on linked sites. We here examine how the presence of 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
more » ... lected sites interacts with demographic parameter estimation. The results demonstrate 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. We propose a potential solution to correct for this mis-inference. 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.
doi:10.1101/2020.04.28.066365 pmid:33501439 pmcid:PMC7836109 fatcat:c3cjdb2srjdrbin4l5fwciuiwy