title: Sickle haemoglobin, haemoglobin C and malaria mortality feedbacks.
abstract: BACKGROUND
  Sickle haemoglobin (HbS) and haemoglobin C (HbC) are both caused by point mutations in the beta globin gene, and both offer substantial malaria protection. Despite the fact that the blood disorder caused by homozygosity for HbC is much less severe than that caused by homozygosity for HbS (sickle cell anaemia), it is the sickle mutation which has come to dominate many old-world malarious regions, whilst HbC is highly restricted in its geographical distribution. It has been suggested that this discrepancy may be due to sickle cell heterozygotes enjoying a higher level of malaria protection than heterozygotes for HbC. A higher fitness of sickle cell heterozygotes relative to HbC heterozygotes could certainly have allowed the sickle cell allele to spread more rapidly. However, observations that carrying either HbC or HbS enhances an individual's capacity to transmit malaria parasites to mosquitoes could also shed light on this conundrum.
  
  
  METHODS
  A population genetic model was used to investigate the evolutionary consequences of the strength of malaria selection being correlated with either HbS frequency or HbC frequency.
  
  
  RESULTS
  If the selection pressure from malaria is positively correlated with the frequency of either HbS or HbC, it is easier for HbS to succeed in the competitive interaction between the two alleles.
  
  
  CONCLUSIONS
  A feedback process whereby the presence of variant haemoglobins increases the level of malaria selection in a population could have contributed to the global success of HbS relative to HbC, despite the former's higher blood disorder cost.
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, W1CE 7HT, UK. bronner.goncalves@lshtm.ac.uk.
authors.forename: Bronner P
authors.initials: BP
authors.lastname: Gonçalves
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK. sunetra.gupta@zoo.ox.ac.uk.
authors.forename: Sunetra
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK. bridget.penman@zoo.ox.ac.uk.
authors.forename: Bridget S
authors.initials: BS
authors.lastname: Penman
mesh_terms: D000483:Alleles; D006444:Hemoglobin C / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008288:Malaria / Q000378:metabolism / Q000401:mortality* / Q000635:transmission; D008962:Models, Theoretical
chemical_list: D006454:Hemoglobins; D006444:Hemoglobin C