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Human Molecular Genetics Advance Access published online on November 28, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm350
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Modiano David#,1, Bancone Germana#,1, Ciminelli Bianca Maria2, Pompei Fiorenza2, Blot Isa3, Simporé Jacques4 and Modiano Guido*,2

1 Dipartimento di Scienze di Sanità Pubblica, University of Rome "La Sapienza", Italy 2 Dipartimento di Biologia, University of Rome "Tor Vergata", Italy 3 Centre National de Transfusion Sanguine, Ouagadougou, Burkina Faso 4 Centre de Recherche Biomoleculaire Pietro Annigoni (CERBA), Ouagadougou, Burkina Faso

* Corresponding author: Guido Modiano Facoltà di Scienze Matematiche, Fisiche e Naturali, Dipartimento di Biologia, Università di Roma "Tor Vergata", Via della Ricerca Scientifica 00133 Rome, Italy, Tel. +39-06-72594341; +39-06-72594330;, Fax +39-06-2023500, e-mail: modiano{at}uniroma2.it

Received September 20, 2007; Revised November 27, 2007; Accepted November 27, 2007

Haemoglobin S (HbS; β6Glu->Val) and HbC (β6Glu->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 (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 fourfold 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, consistently 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.

# These authors contributed equally to this work.


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