Human Molecular Genetics Advance Access originally published online on November 28, 2007
Human Molecular Genetics 2008 17(6):789-799; doi:10.1093/hmg/ddm350
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Haemoglobin S and haemoglobin C: ‘quick but costly’ versus ‘slow but gratis’ genetic adaptations to Plasmodium falciparum malaria
1 Dipartimento di Scienze di Sanità Pubblica, University of Rome ‘La Sapienza’, Rome, Italy 2 Dipartimento di Biologia, University of Rome ‘Tor Vergata’, Rome, Italy 3 Centre National de Transfusion Sanguine, Ouagadougou, Burkina Faso 4 Centre de Recherche Biomoleculaire Pietro Annigoni (CERBA), Ouagadougou, Burkina Faso
* To whom correspondence should be addressed at: Facoltà di Scienze Matematiche, Fisiche e Naturali, Dipartimento di Biologia, Università di Roma ‘Tor Vergata’, Via della Ricerca Scientifica, 00133 Rome, Italy. Tel: +39 0672594341; +39 0672594330; Fax: +39 062023500; Email: modiano{at}uniroma2.it
Received September 20, 2007; Accepted November 27, 2007
Haemoglobin S (HbS; β6Glu
Val) and HbC (β6GluLys) 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 (SBenin) and the C alleles are common (0.05 and 0.13). Here we show that: both C and SBenin are monophyletic; C has accumulated a 4-fold higher recombinational and DNA slippage haplotypic variability than the SBenin 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.
The authors with it to be known that, in their opinion, the first two authors should be regarded as joint Authors.