Haemoglobin S and haemoglobin C : ’quick but costly’ versus ’slow but gratis’ genetic adaptations to Plasmodium falciparum malaria.

Modiano D, Bancone G, Ciminelli BM, Pompei F, Blot I, Simporé J, Modiano G.

Hum Mol Genet. 2008 Mar 15 ;17(6):789-99. Epub 2007 Nov 28. Erratum in : Hum Mol Genet. 2008 Jul 1 ;17(13):2070.
PMID : 18048408 [PubMed - indexed for MEDLINE]



Haemoglobin S (HbS ; beta6Glu—>Val) and HbC (beta6Glu—>Lys) strongly protect against clinical Plasmodium falciparum malaria. HbS, which is lethal in homozygosity, has a multi-foci origin and a widespread geographic distribution in sub-Saharan Africa and Asia whereas HbC, which has no obvious CC segregational load, occurs only in a small area of central West-Africa. To address this apparent paradox, we adopted two partially independent haplotypic approaches in the Mossi population of Burkina Faso where both the local S (S(Benin)) and the C alleles are common (0.05 and 0.13). Here we show that : both C and S(Benin) are monophyletic ; C has accumulated a 4-fold higher recombinational and DNA slippage haplotypic variability than the S(Benin) allele (P = 0.003) implying higher antiquity ; for a long initial lag period, the C alleles did apparently remain very few. These results, consistent with epidemiological evidences, imply that the C allele has been accumulated mainly through a recessive rather than a semidominant mechanism of selection. This evidence explains the apparent paradox of the uni-epicentric geographic distribution of HbC, representing a ’slow but gratis’ genetic adaptation to malaria through a transient polymorphism, compared to the polycentric ’quick but costly’ adaptation through balanced polymorphism of HbS.

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