Let the genotype frequencies of the sickle homozygote, heterozygote, and wild-type homozygote be p2, 2pq, and q2, respectively. Let the corresponding relative fitnesses be 0, 1+s, and 1, respectively.2 Then, at equilibrium, s=(p/1−2p). For each of the five continental African samples in the 1000 Genomes Project Phase 3 release version 5a, we estimated the effective population size Ne on the basis of the heterozygosities of all single-nucleotide polymorphisms (i.e., diallelic, triallelic, and quadrallelic) by assuming a mutation rate of 0.97×10−8 mutations per site per generation.34 We then took the harmonic mean of the five Ne estimates. Assuming one initial copy of the mutant allele, we simulated 1,000 generations under a combination of random genetic drift and balancing selection. We repeated this process 1,000 times.