The impact of linked selection on demographic inference: insights from the Inverse Instantaneous Coalescence Rate (IICR).

Simon Boitard

Centre de Gestion et de Biologie des Populations (CBGP), Montpellier, France

Link to seminar: https://umontpellier-fr.zoom.us/webinar/register/WN_78nPCMUWRLuVKrLwLwvMEg

The relative contribution of selection and neutrality in shaping species genetic diversity is one of the most central and controversial questions in evolutionary theory. Genomic data provide growing evidence that linked selection, i.e. the modification of genetic diversity at neutral sites through linkage with selected sites, might be pervasive over the genome. Several studies proposed that linked selection could be modelled as first approximation by a local reduction (e.g. purifying selection, selective sweeps) or increase (e.g. balancing selection) of effective population size (Ne). At the genome-wide scale, this leads to a large variance of Ne from one region to another, reflecting the heterogeneity of selective constraints and recombination rates between regions. Following this modelling framework, we investigate here the consequences of this variation of Ne on the genome-wide distribution of coalescence times. The underlying motivation concerns the impact of linked selection on demographic inference, because the genome-wide distribution of coalescence times is at the heart of several demographic inference approaches including the PSMC method of Li and Durbin. Using the concept of IICR (Inverse Instantaneous Coalescence Rate), we demonstrate that in a panmictic population, linked selection always results in a spurious apparent decrease of Ne along time. We quantify the expected magnitude of this decrease in humans and Drosophila melanogaster, based on Ne distributions inferred from real data in these species. We also find that the effect of linked selection can be significantly reduced by that of population structure.

Recent publications:

Boitard, S., Paris, C., Sevane, N., Servin, B & Dunner, S. (2021). Gene banks as reservoirs to detect recent selection: the example of the Asturiana de los Valles bovine breed. Frontiers in Genetics (provisionally accepted).

Soto, A. A., Mourato, B., Nguyen, K., Boitard, S., Valcarce, W. R. R., Noûs, C., ... & Chikhi, L. (2020). Inferring number of populations and changes in connectivity under the n-island model. bioRxiv.

C. Paris, B. Servin & S. Boitard (2019). Inference of selection from genetic time series using various parametric approximations to the Wright-Fisher model. G3: Genes, Genomes, Genetics, 9(12), 4073-4086.

https://genphyse.toulouse.inra.fr/people/boitard/simon