Re: Malaria resistance

https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006560   This is a population genetic study on the DARC allele that is associated with resistance to Plasmodium vivax.  The DARC receptor usually detects foreign antigens and signals a chemokine response, but a variant exists that messes up the normal transcription regulation site and the receptor is no longer expressed in red blood cells.  P. vivax normally uses the DARC receptor to gain access into the red blood cells, and when it isn't there they can't infect the cell.  So if you are homozygous for the resistant null allele you are highly protected against P. vivax infection.  There is likely negative consequences to not expressing DARC in red blood cells because the allele has never been fixed in the populations subject to infection by P. vivax, and there is a low level of heterozygotes left in populations, and where P. vivax is not a problem the frequency of the resistant allele is very low.  The paper claims "fixation" for the resistant allele in parts of Africa, but heterozygotes existed in all populations, but the allele frequency went to 0.99)
 Any negative consequences are not as bad as sickle cell anemia resistance to Plasmodium falciparum.  For sickle cell in the past the allele frequency could only get to a little over 0.37 (over 75% of the adult population could be heterozygous and resistant to malaria). Homozygotes have sickle cell anemia and in the past usually died before becoming adults, but there is a higher survival rate with implementation of modern medicine.  For the DARC allele the allele frequency can go to 0.99 in populations infected by P. vivax.
 They did an analysis of the alleles and claim that the resistant allele had been segregating in the African population for sometime, and likely was taken out of Africa with the wave of Modern humans that left around 60,000 years ago.  The resistant allele was part of the standing genetic variation, but may not have been more than 0.1% (allele frequency of 0.001 or 1 in 500 individuals were carriers).  Apparently the sequence analysis indicates that P. vivax did not become an issue in sub-saharan Africa until less than 10,000 years ago and resulted in the selection of the resistant allele and it subsequently becoming the most common allele in sub-saharan Africa.
 Ron Okimoto