Multi-population genomic analysis of malaria parasites indicates local selection and differentiation at the gdv1 locus regulating sexual development

Duffy, C. W. et al. (2018) Multi-population genomic analysis of malaria parasites indicates local selection and differentiation at the gdv1 locus regulating sexual development. Scientific Reports, 8, 15763. (doi: 10.1038/s41598-018-34078-3) (PMID:30361631) (PMCID:PMC6202401)

Abstract

Parasites infect hosts in widely varying environments, encountering diverse challenges for adaptation. To identify malaria parasite genes under locally divergent selection across a large endemic region with a wide spectrum of transmission intensity, genome sequences were obtained from 284 clinical Plasmodium falciparum infections from four newly sampled locations in Senegal, The Gambia, Mali and Guinea. Combining these with previous data from seven other sites in West Africa enabled a multi-population analysis to identify discrete loci under varying local selection. A genome-wide scan showed the most exceptional geographical divergence to be at the early gametocyte gene locus gdv1 which is essential for parasite sexual development and transmission. We identified a major structural dimorphism with alternative 1.5 kb and 1.0 kb sequence deletions at different positions of the 3′-intergenic region, in tight linkage disequilibrium with the most highly differentiated single nucleotide polymorphism, one of the alleles being very frequent in Senegal and The Gambia but rare in the other locations. Long non-coding RNA transcripts were previously shown to include the entire antisense of the gdv1 coding sequence and the portion of the intergenic region with allelic deletions, suggesting adaptive regulation of parasite sexual development and transmission in response to local conditions.

• Item Type: Articles
• Additional Information: Te research was supported by funding from the European Research Council (AdG-2011-294428), the Medical Research Council of the UK (G1100123, MC_EX_MR/K02440X/1, and MC_EX_MR/J002364/1), the Wellcome Trust (090770/Z/09/Z), the Biotechnology and Biological Sciences Research Council of the UK (London Interdisciplinary Doctoral Programme studentship), and the Royal Society (AA110050).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Otto, Professor Thomas
• Authors: Duffy, C. W., Amambua-Ngwa, A., Ahouidi, A. D., Diakite, M., Awandare, G. A., Ba, H., Tarr, S. J., Murray, L., Stewart, L. B., D’Alessandro, U., Otto, T. D., Kwiatkowski, D. P., and Conway, D. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Scientific Reports 8:15763
• Publisher Policy: Reproduced under a Creative Commons License