Host genetic factors can confer resistance against malaria, raising the question of whether this has led to an evolutionary adaptation of parasite populations.
In this study, scientists searched for an association between candidate host and parasite genetic variants in 3,346 Gambian and Kenyan children ascertained with severe malaria due to Plasmodium falciparum.
They identified a strong association between sickle hemoglobin (HbS) in the host and three regions of the parasite genome, that is not explained by population structure or other covariates, and that is replicated in additional samples.
The HbS-associated alleles include nonsynonymous variants in the acyl-CoA synthetase family member2–4 PfACS8 on the second region of a chromosome, and in a region containing structural variation on the chromosome.
The alleles are in strong linkage disequilibrium and have frequencies that covary with the frequency of HbS across populations, in particular being much more common in Africa than in other parts of the world.
The estimated protective effect of HbS against severe malaria, as determined by comparison of cases with population controls, varies greatly according to the parasite genotype at these three loci.
These findings open up a new avenue of inquiry into the biological and epidemiological significance of the HbS-associated polymorphisms in the parasite genome, and the evolutionary forces that have led to their high frequency and strong linkage disequilibrium in African P. falciparum populations.
Published: 09 December 2021
source:
https://www.nature.com/articles/s41586-021-04288-3
https://doi.org/10.1038/s41586-021-04288-3
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