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: Bronner P Gonçalves, Sunetra Gupta, Bridget S Penman
• Journal: Malaria journal (Malar J) Vol. 15 Pg. 26 (Jan 12 2016) ISSN: 1475-2875 [Electronic] England
• PMID: 26753833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hemoglobins
• Hemoglobin C

Topics

• Alleles
• Hemoglobin C (metabolism)
• Hemoglobins (metabolism)
• Humans
• Malaria (metabolism, mortality, transmission)
• Models, Theoretical