2008 Kustu and Inwood 2006), or not in transport but in erythrocyte membrane structure ( Westhoff 2004 Westhoff and Wylie 2006).

2000) or carbon dioxide ( Endeward et al. The human Rh blood group system is a collection of antigens expressed on erythrocyte cell membranes ( Avent and Reid 2000) that may play a role in the transport of ammonia ( Marini et al. Therefore, the potential fitness benefits of the RHCE C allele are currently unknown but merit further exploration. RhCE function is not well understood, but the C/c antigenic variant is clinically relevant and can result in hemolytic disease of the newborn, albeit much less commonly and severely than that related to the D-negative blood type. We unexpectedly observed evidence for positive selection on the C allele of RHCE in non-African populations (on chromosomes with intact copies of the RHD gene) in the form of an unusually high F ST value and the high frequency of a single haplotype carrying the C allele. Therefore, once such a frequency was achieved, it could have been maintained by a relatively small amount of genetic drift. However, our simulations recapitulate previous findings that selection on the RHD deletion is frequency dependent, and weak or absent near 0.5. Thus, the initial rise to intermediate frequency of the RHD deletion in European populations may simply be explained by genetic drift/ founder effect, or by an older or more complex sweep that we are insufficiently powered to detect. We found no evidence that positive natural selection affected the frequency of the RHD deletion. In this study, we used new molecular and genomic data generated from four HapMap population samples to test the idea that positive selection for an as-of-yet unknown fitness benefit of the RHD deletion may have offset the otherwise negative fitness effects of hemolytic disease of the newborn.

Given the deleterious fitness consequences of this disease, the appreciable frequencies in European populations of the responsible RHD gene deletion variant (for example, 0.43 in our study) seem surprising. Prior to medical treatments and interventions developed in the last century, the D-positive children of D-negative women were at risk for hemolytic disease of the newborn, if the mother produced anti-D antibodies following sensitization to the blood of a previous D-positive child. The evolutionary history of variation in the human Rh blood group system, determined by variants in the RHD and RHCE genes, has long been an unresolved puzzle in human genetics.

Rh a negative blood type