Resolving drug selection and migration in an inbred South American Plasmodium falciparum population with identity-by-descent analysis.
Creators: name: Carrasquilla, Manuela
name: Early, Angela M
name: Taylor, Aimee R
name: Knudson Ospina, Angélica
name: Echeverry, Diego F
name: Anderson, Timothy JC
name: Mancilla, Elvira
name: Aponte, Samanda
name: Cárdenas, Pablo
name: Buckee, Caroline O
name: Rayner, Julian C
name: Sáenz, Fabián E
name: Neafsey, Daniel E
name: Corredor, Vladimir
Publisher: name: Apollo - University of Cambridge Repository
Year: 2022
Subjects: Research Article
People and places
Biology and life sciences
Medicine and health sciences

description: Acknowledgements: From Colombia we thank the Guapi communities, the Secretaría Municipal de Salud del Cauca and Secretaría Departamental de Salud del Cauca, as well as the VeuPathDB outreach team for assistance in the GoldenGate decoding SNP process, with the Colombian samples. We thank Marco Galardini for bioinformatics support and helpful comments. In particular, we thank the communities in Esmeraldas and San Lorenzo and the Health districts (especially Drs. Javier Obando, César Diaz and Julio Valencia).
description: Funder: Ministerio de Salud Pública del Ecuador
description: The human malaria parasite Plasmodium falciparum is globally widespread, but its prevalence varies significantly between and even within countries. Most population genetic studies in P. falciparum focus on regions of high transmission where parasite populations are large and genetically diverse, such as sub-Saharan Africa. Understanding population dynamics in low transmission settings, however, is of particular importance as these are often where drug resistance first evolves. Here, we use the Pacific Coast of Colombia and Ecuador as a model for understanding the population structure and evolution of Plasmodium parasites in small populations harboring less genetic diversity. The combination of low transmission and a high proportion of monoclonal infections means there are few outcrossing events and clonal lineages persist for long periods of time. Yet despite this, the population is evolutionarily labile and has successfully adapted to changes in drug regime. Using newly sequenced whole genomes, we measure relatedness between 166 parasites, calculated as identity by descent (IBD), and find 17 distinct but highly related clonal lineages, six of which have persisted in the region for at least a decade. This inbred population structure is captured in more detail with IBD than with other common population structure analyses like PCA, ADMIXTURE, and distance-based trees. We additionally use patterns of intra-chromosomal IBD and an analysis of haplotypic variation to explore past selection events in the region. Two genes associated with chloroquine resistance, crt and aat1, show evidence of hard selective sweeps, while selection appears soft and/or incomplete at three other key resistance loci (dhps, mdr1, and dhfr). Overall, this work highlights the strength of IBD analyses for studying parasite population structure and resistance evolution in regions of low transmission, and emphasizes that drug resistance can evolve and spread in small populations, as will occur in any region nearing malaria elimination.