Evolutionary structure of Plasmodium falciparum major variant surface antigen genes in South America: Implications for epidemic transmission and surveillance

Abstract

Strong founder effects resulting from human migration out of Africa have led to geographic variation in single nucleotide polymorphisms (SNPs) and microsatellites (MS) of the malaria parasite, Plasmodium falciparum. This is particularly striking in South America where two major founder populations of P. falciparum have been identified that are presumed to have arisen from the transatlantic slave trade. Given the importance of the major variant surface antigen of the blood stages of P. falciparum as both a virulence factor and target of immunity, we decided to investigate the population genetics of the genes encoding “Plasmodium falciparum Erythrocyte Membrane Protein 1” (Pf EMP1) among several countries in South America, in order to evaluate the transmission patterns of malaria in this continent. Deep sequencing of the DBLα domain of var genes from 128 P. falciparum isolates from five locations in South America was completed using a 454 high throughput sequencing protocol. Striking geographic variation in var DBLα sequences, similar to that seen for SNPs and MS markers, was observed. Colombia and French Guiana had distinct var DBLα sequences, whereas Peru and Venezuela showed an admixture. The importance of such geographic variation to herd immunity and malaria vaccination is discussed.

Evolutionary analyses of the major variant surface antigen-encoding genes reveal population structure of Plasmodium falciparum within and between continents

“…Our comparisons to a global DBLα type dataset and JHMM analysis allowed us to further investigate the “Out of Africa” hypothesis and build upon previous work [ 31 , 39 ]. We compared each South American isolate to all non-South American isolates from Africa and Asia/Oceania to determine the proportion of DBLα type matching proportions among isolates.…”

“…To construct such a matrix we used the pipeline described in Ruybal-Pesántez et al (2017) [ 40 ]. Using this matrix, comparisons were made to the phylogeny-based approach of Tessema et al (2015) [ 38 ] ( S8 Fig ) as well as the admixture approach of Rougeron et al (2017) [ 39 ] ( S9 and S10 Figs). Neither of these approaches was able to reconstruct the same level of detailed population structure as the JHMM method.…”

“…We found evidence for geographic variation in these types and we reason that local adaptation of P . falciparum populations to distinct selective pressures, vector populations, and hosts may have played a role in shaping these patterns [ 39 , 41 ].…”

“…Tessema et al (2015) [ 38 ] further investigated the DBLα type population structure in PNG, identifying fine-scale population structure of the DBLα type repertoires at the village level. Rougeron et al (2017) [ 39 ] analyzed a collection of isolates from South America, observing a smaller population size of DBLα types than has been reported in other regions, and suggested that the DBLα type population structure mirrored that found in the SNP and microsatellite analysis of Yalcindag et al (2012) [ 31 ]. Ruybal-Pesántez et al (2017) [ 40 ] investigated DBLα type diversity across six sites in Uganda, identifying high diversity and little repertoire overlap.…”

“…Subsequent network analyses and stochastic simulations that consider both epidemiological and evolutionary processes confirmed that frequency-dependent immune selection can structure DBLα type repertoires [ 42 ]. Of note, these molecular epidemiological studies showed high diversity of DBLα types and repertoires, with individual DBLα types conserved in space and time within and between sampling sites [ 36 , 39 – 41 ] despite in vitro predictions of rapid evolution by mitotic recombination [ 27 , 29 ].…”