There is an interesting new article that confirms by statistical means the long held theory that sickle cell disease exists in a dynamic equilibrium with the deadly disease of malaria, at least in general.
Federic B. Piel et al., Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis. Nature communications 2010. Open access.
What I find interesting is not so much the confirmation of a correlation in Africa and Europe but the lack of confirmation in Asia and Oceania, where malaria exists endemically too and, unlike the case of America, the discontinuity cannot be explained by loss of the sickle cell allele in the arctic latitudes (Beringia). In fact the peculiarities of the geographical distribution of sickle cell disease versus endemic malaria are very intriguing:
|Fig. 1 (click to enlarge)|
I understand that, in the case of Africa, the correlation is very strong, though not totally lineal. For instance the HbS (sickle cell) allele is lacking in wide areas of malaria endemism: The Horn, Southern Africa (including Bantu Mozambique but not Austronesian Madagascar), NW Africa...
So somehow these populations have managed to get rid of the sickle cell anemia in spite of being exposed to malaria in hyperendemic form. This alone is pretty interesting in itself, specially as it involves Bantu populations that are supposed to have expanded recently.
In Europe we have two situations: Greece and Albania where sickle cell exists in moderate frequencies and the rest, where it is unheard of. While Greece is one of the malaria epidemic areas, there are others where the parasite has only been eradicated in the 20th century: Italy and Iberia specially. However no sickle cell exists there. This case is very suggestive, statistics apart, with the spread of Y-DNA E1b1b1a2 (V13), haplogroup that is most concentrated in the SW Balkans.
But most intriguing of all may be Asia. The presence of the allele in West Asia makes some good sense because of its prehistorical (and maybe also historical) interactions with Africa, so the HbS allele had all opportunities to arrive, really.
But what about further East. We know of no particular "recent" genetic flow into South Asia that could explain the relatively high frequencies found in India, mostly in areas of lesser West Eurasian influence. The connections with Africa are even less likely (some small populations of recent African origin do exist but they cannot possibly have influenced the majority in such dramatic way in such short time).
It could be something arrived in the migration out of Africa of course, yet, on the other hand, further East there is no trace of the HbS allele. But malaria is found again in hyperendemic form in all SE Asia and Near Melanesia. Why? No idea. While the sampling is low density, it does seem like most relevant areas have been tested (map a), including Melanesia, Australian Aborigines, Indonesia and even Andaman.
So why these irregularities? Which are the founder effects implied? One can imagine that the northernmost historical malaria areas were free from the parasite in the Ice Age, but surely this was not the case of the Asian tropical belt. Did some sort of lifestyle, like choosing to dwell where marine breeze kept mosquitoes at bay (a usual common sense practice in tropical coasts as far as I know) help Eastern Eurasian founders prevent this disease, making the allele unnecessary? Was instead the HbS allele "stored" (by founder effect) in some South Asian demographic reservoir (and only there), gradually expanding to some nearby malaria affected areas but never participating of the colonization of the Far East by mere chance?
What about the West, where the HbS allele is also mostly absent? Here at least one could argue that malaria was probably absent in the Pleistocene, so the HbS allele was logically selected against (even heterozygous types have some lesser disadvantages if malaria is not present to compensate for them).
It is a single SNP (rs334) which encodes all this matter, so it is not possible to trace it phylogenetically in any way.
Intriguing in any case.