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Methods to Investigate the Regulatory Role of Small RNAs and Ribosomal Occupancy of Plasmodium falciparum
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Published on: December 4, 2015

Hypervariable antigen genes in malaria have ancient roots.

Martine M Zilversmit1, Ella K Chase, Donald S Chen

  • 1National Institute of Allergy of Infectious Disease, National Institutes of Health, 12735 Twinbrook Parkway, Rockville, MD 20852, USA. martine.zilversmit@nih.gov

BMC Evolutionary Biology
|June 4, 2013
PubMed
Summary
This summary is machine-generated.

The Plasmodium falciparum var gene family, crucial for malaria virulence, shows a surprisingly old and stable structure, predating the split between P. falciparum and P. reichenowi. Recombination drives diversity within this ancient gene family.

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Area of Science:

  • Genomics
  • Evolutionary Biology
  • Parasitology

Background:

  • The var genes encode erythrocyte membrane proteins 1 (PfEMP1), mediating cytoadherence of Plasmodium falciparum-infected red blood cells.
  • PfEMP1-mediated cytoadherence and var gene switching contribute to malaria virulence and immune evasion.
  • While var gene diversity is studied, their evolutionary origins remain largely unknown.

Purpose of the Study:

  • To investigate the evolutionary history and origin of the var gene family.
  • To compare the var gene repertoire and structure between Plasmodium falciparum and Plasmodium reichenowi.

Main Methods:

  • Utilized a novel hidden Markov model-based approach for sequence analysis.
  • Compared var gene DBLα domains from P. falciparum isolates (3D7, HB3) and P. reichenowi.
  • Assembled var sequences from additional isolates and species.

Main Results:

  • The var gene family is similarly large in P. falciparum (61 in 3D7, 48 in HB3) and P. reichenowi (≥51 genes).
  • Identified large homologous sequence blocks in DBLα domains, indicating conserved structure before species divergence (2.5-6 million years ago).
  • Recombination plays a significant role in establishing and maintaining sequence diversity within the var gene family.

Conclusions:

  • The fundamental structure of the var gene family is ancient and stable, despite high within- and between-species diversity.
  • Conserved domain structure and sequences between P. falciparum and P. reichenowi have implications for developing new experimental models.
  • Findings inform studies on malaria pathology, immunology, and the population genetics of var genes and virulence phenotypes.