Natural selection does not affect the estimates of effective population size based on linkage disequilibrium

Abstract

The effective population size ( N e ) is a key parameter to quantify the magnitude of genetic drift and inbreeding, with important implications in human evolution. The increasing availability of high-density genetic markers allows the estimation of historical changes in N e across time using measures of genome diversity or linkage disequilibrium between markers. Selection is expected to reduce diversity and N e , and this reduction is modulated by the heterogeneity of the genome in terms of recombination rate. Here we investigate by computer simulations the consequences of selection (both positive and negative) and of recombination rate heterogeneity in the estimation of historical N e . We also investigate the relationship between diversity parameters and N e across the different regions of the genome using human marker data. We show that the estimates of historical N e obtained from linkage disequilibrium between markers ( N e LD ) are virtually unaffected by selection. In contrast, those estimates obtained by coalescence mutation-recombination-based methods can be strongly affected by it, what could have important consequences for the estimation of human demography. The simulation results are supported by the analysis of human data. The estimates of N e LD obtained for particular genomic regions do not correlate with recombination rate, nucleotide diversity, polymorphism, background selection statistic, minor allele frequency of SNPs, loss of function and missense variants and gene density. This suggests that N e LD measures are merely indicative of demographic changes in population size across generations.