The effect of gene flow and thalassaemia start frequencies on the formation of hotspots, with and without epistasis. Panels (a) and (b) illustrate the results of a scenario where βS was first introduced 100 generations ago, into a population containing fixed (and identical) frequencies of both α and β thalassaemia (y axis). Malaria selection is applied to every deme at a level of 0.005 years−1, and after its first introduction, βS is assumed to re-challenge the population in 100% of subsequent generations. The colour of each cell in the heatmap indicates the average number of hotspots observed per metapopulation over 100 simulations at that parameter combination. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)