Coupling ecology and evolution: malaria and the S-gene across time scales.

Malaria has long been a scourge to humans. The exceptionally high mortality in some regions has led to strong selection for resistance, even at the cost of increased risk of potentially fatal red blood cell deformities in some offspring. In particular, genes that confers resistance to malaria when they appear in heterozygous individuals are known to lead to sickle-cell anemia, or other blood diseases, when they appear in homozygous form. Thus, there is balancing selection against the evolution of resistance, with the strength of that selection dependent upon malaria prevalence. Over longer time scales, the increased frequency of resistance in a population might be expected to decrease the frequency of malaria and reduce selection for resistance. However, possession of the sickle-cell gene leads to longer-lasting parasitaemia in heterozygote individuals, and therefore the presence of resistance may actually increase infection prevalence. In this paper, we explore the interplay among these processes, operating over very different time scales. In particular, we show that on the fast time scale of malarial dynamics, the disease level reaches an equilibrium; on the slower, evolutionary time scale, this equilibrium tracks gene frequency. We analyze the slow time scale dynamics to investigate the impact of malaria on the evolution of resistance.