Genetic dynamics of the Duffy antigen receptor for chemokines gene and Plasmodium vivax circulation within sub-Saharan Africa

INTRODUCTION: Duffy antigen receptor for chemokines (DARC) is a transmembrane receptor (glycoprotein) expressed on human red blood cells. Sub-Saharan Africa (sSA) individuals, who suffer the most of the global malaria burden, predominantly carry a Duffy negative phenotype. Expression of this gene (found among Duffy-positive individuals) is known to be essential for P. vivax invasion of RBCs. While P. falciparum is the predominant Plasmodium in sSA, the upward trend in P. vivax infection is a major threat to the malaria eradication programme in the region. Since Duffy null individuals (homozygous negative) lack DARC expression, we investigated the DARC gene dynamics in relation to the emerging presence of P. vivax infections in a previously predominant P. falciparum endemic region. 

METHODS: A total of 223 DARC genes were retrieved from the NCBI database across various countries, Nigeria, Cameroon, Ethiopia, Madagascar and South Africa and were used for population dynamic analysis using different population genetic metrics. 

FINDINGS: Among these sSA countries, South Africa showed the most haplotype and nucleotide diversity compared to other parts of sSA. Various selection pressures were observed in Western Africa and the Central African Republic. Population structure analysis revealed DARC population clustering of Cameroon, Nigeria and Ethiopia (despite Ethiopia's geographic distance), suggestive of shared ancestry and minimal DARC locus divergence. Conversely, South Africa and Madagascar showed a distinct genetic lineage reflecting differences in evolutionary pressures. 

CONCLUSION: Our analysis suggests minimal genetic diversity within sSA with evidence of selection potentially attributed to the recent emergence of P. vivax infections. However, greater diversity was observed in South Africa. Evidence of selection of this gene and detection of P. vivax among Duffy-null individuals in the other regions is truly a public health concern.