Population Genomics of the Immune Evasion (var) Genes of Plasmodium falciparum

PLoS Pathogens

Karen P Day¹  Gilean A. V McVean²  Heather Imrie²  Aleksandra Leliwa-Sytek²  Florence Migot-Nabias³  Alyssa E Barry⁴  Stuart M Brown⁴  Livingston Tavul⁴ 

[1] Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon;Department of Zoology, University of Oxford, Oxford, United Kingdom;Papua New Guinea Institute for Medical Research, Madang, Papua New Guinea;Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom

关键词: Sequence alignment;    Multiple alignment calculation;    Population genetics;    Species diversity;    Malarial parasites;    Genomics;    Malaria;    Plasmodium;   

DOI  :  10.1371/journal.ppat.0030034

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Var genes encode the major surface antigen (PfEMP1) of the blood stages of the human malaria parasite Plasmodium falciparum. Differential expression of up to 60 diverse var genes in each parasite genome underlies immune evasion. We compared the diversity of the DBLα domain of var genes sampled from 30 parasite isolates from a malaria endemic area of Papua New Guinea (PNG) and 59 from widespread geographic origins (global). Overall, we obtained over 8,000 quality-controlled DBLα sequences. Within our sampling frame, the global population had a total of 895 distinct DBLα “types” and negligible overlap among repertoires. This indicated that var gene diversity on a global scale is so immense that many genomes would need to be sequenced to capture its true extent. In contrast, we found a much lower diversity in PNG of 185 DBLα types, with an average of approximately 7% overlap among repertoires. While we identify marked geographic structuring, nearly 40% of types identified in PNG were also found in samples from different countries showing a cosmopolitan distribution for much of the diversity. We also present evidence to suggest that recombination plays a key role in maintaining the unprecedented levels of polymorphism found in these immune evasion genes. This population genomic framework provides a cost effective molecular epidemiological tool to rapidly explore the geographic diversity of var genes.

【 授权许可】

CC BY