No, it has not"popped on and off" that's not how it works. Maybe this will help:
Discussion:
A strong geographical link between the highest HbS allele frequencies and high malaria endemicity was observed at the global scale (
Fig. 4a), but this observation is influenced primarily by the relationship found in Africa (
Fig. 4b). The gradual increase in HbS allele frequencies from epidemic areas to holoendemic areas in Africa is consistent with the hypothesis that malaria protection by HbS involves the enhancement of not only innate but also acquired immunity to
P. falciparum31. Interactions with haemoglobin C
32,
33 might explain the lower HbS allele frequencies in West Africa
24. Despite the presence of large malarious areas, HbS is absent in the Americas and in large parts of Asia
2 (
Fig. 1a). Therefore, no geographical confirmation of the malaria hypothesis could be identified in these regions. Although several haemoglobin variants have been identified in the Americas
5, none of the malaria protective polymorphisms have been observed in the indigenous populations of this continent
19. The combination of the low likelihood of an independent HbS mutation arising and a relatively low selection pressure (due to the absence of holoendemic areas, the more recent arrival of malaria, as well as the predominance of
P. vivax) could contribute to the absence of HbS in that region. In Southeast Asia
34, other malaria protective polymorphisms have been identified (haemoglobin E (HbE), the thalassaemias, glucose-6-phosphate dehydrogenase deficiency and Southeast Asian ovalocytosis) and levels of malaria endemicity were relatively high. It is suspected that HbE and Southeast Asian ovalocytosis in particular may have had epistatic interactions
35,
36, altering the selection pressure for the HbS gene in that region
37. The complex social structure and the predominance of
P. vivax38 are also considered as likely to contribute to the unresolved geographical relationship in India. Ongoing work to create an open-access database for several malaria protective polymorphisms will allow more comprehensive distribution mapping and improve our understanding of their geographical interaction.
Substantial variations in HbS allele frequencies over short distances (up to 10% over <50 km) have been described in literature
5, for example, in relation to altitude, rainfall or
Anopheles survival
39, which underlie variations in selection
40. Such spatial heterogeneity was observed in the geodatabase. The combination of a detailed georeferencing process, the use of a geostatistical model able to incorporate the multiple scales of variation within the data and a semicontinuous gradient of HbS allele frequencies allowed us to describe the global distribution and the high geographical variability of this gene more rigorously than achieved in previous maps
17,
18,
19. The uncertainty measure (see
Fig. 2) provides an important estimate of the limitations associated with a retrospective data set, and can highlight areas prone to small population samples and/or areas lacking observations (for example, New Zealand).
Among the factors that might contribute to the heterogeneity observed in the HbS allele frequency in hyperendemic areas in Africa (
Fig. 3b), we identified (i) a component of geographical sampling error from an 'opportunistic sample' of surveys that we were able to source from literature; (ii) the kinetics of the spread of the HbS gene, which leads to an exponential increase in areas in which a selective pressure appears, but to a much slower decrease in areas in which the selective pressure disappears
41; (iii) long-term (sociological or physical) isolation of local populations, which could result in pockets of lower HbS allele frequencies ...
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060623/