Randrianarivelojosia, M. | bioRxiv Science

bioRxiv2024

Regional Plasmodium falciparum subpopulations and malaria transmission connectivity in Africa were detected with an enlarged panel of genome-wide microsatellite loci

Unravelling the genetic diversity of Plasmodium falciparum malaria parasite provides critical information on how populations are affected by interventions and the environment, especially the evolution of molecular markers associated with parasite fitness and adaptation to drugs and vaccines. This study expands previous studies based on small sets of microsatellite loci, which often showed limited substructure in African populations of P. falciparum. Combining several short tandem repeat detection algorithms, we genotyped and analysed 2329 polymorphic microsatellite loci from next-generation sequences of 992 low-complexity P. falciparum isolates from 15 sub-Saharan African countries. Based on pairwise relatedness, we identified seven subpopulations and gene flow between the Central and Eastern African populations. The most divergent subpopulation was from Ethiopia, while unexpected unique subpopulations from Gabon and Malawi were resolved. Isolates from the Democratic Republic of Congo shared ancestry with multiple regional populations, suggesting a possible founder population of P. falciparum from the Congo basin, where there was stronger geneflow eastwards to Tanzania, and Kenya. and Malawi. The most differentiated microsatellite loci were those around the P. falciparum dihydropteroate synthase (Pfdhps) gene associated with sulphadoxine resistance. Haplotypes around the Pfdhps gene separated the West, Central, and East Africa parasite populations into distinct clusters, suggesting independent local evolution of Pfdhps-associated sulphadoxine resistance alleles in each African region. Overall, this study presents genome-wide microsatellites as markers for resolving P. falciparum population diversity, structure, and evolution in populations like Africa, where there is high gene flow.

genomics↗

bioRxiv2021

Differential transcriptomic response of Anopheles arabiensis to Plasmodium vivax and Plasmodium falciparum infection

Plasmodium vivax malaria is now recognized as the second most dangerous parasitic threat to human health with the regular decrease of Plasmodium falciparum worldwide over recent decades. A very limited numbers of studies address the interaction of P. vivax with its Anopheles mosquito vectors. Those studies were conducted in P. vivax endemic countries with P.vivax local major vectors for which limited genomic and genetic tools are available. Despite the presence of P. vivax in several African countries and increasing reports on its occurrence in many others, there is virtually no data on the molecular responses of Anopheles arabiensis, a major African mosquito vector, to P. vivax, which limits the development of further "mosquito-targeted" interventions aimed at reducing P. vivax transmission. Taking advantage of the situation of Madagascar where P. falciparum, P. vivax and An. arabiensis are present, we explore the molecular responses of An. arabiensis towards these two human malaria parasites. RNA sequencing on RNAs isolated from mosquito midguts dissected at the early stage of infection (24 hours) was performed using mosquitoes fed on the blood of P. vivax and P. falciparum gametocyte carriers in a field station. From a de novo assembly of An. arabiensis midgut total RNA transcriptome, the comparative analysis revealed that a greater number of genes were differentially expressed in the mosquito midgut in response to P. vivax (209) than to P. falciparum (81). Among these, 15 common genes were identified to be significantly expressed in mosquito midgut 24 hours after ingesting P. vivax and P. falciparum gametocytes, including immune responsive genes and genes involved in amino-acid detoxification pathways. Importantly, working with both wild mosquitoes and field circulating parasites, our analysis revealed a strong mosquito genotype by parasite genotype interaction. Our study also identified 51 putative long non-coding RNAs differentially expressed in An. arabiensis mosquito infected midgut. Among these, several mapped to the published An. arabiensis genome at genes coding immune responsive genes such as gambicin 1, leucine-rich repeat containing genes, either on sense or antisense strands. This study constitutes the first comparison of An. arabiensis molecular interaction with P. vivax and P. falciparum, investigating both coding and long non-coding RNAs for the identification of potential transcripts, that could lead to the development of novel approaches to simultaneously block the transmission of vivax and falciparum malaria.

microbiology↗