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Comparative 3D genome organization in apicomplexan parasites.

Evelien M Bunnik¹, Aarthi Venkat², Jianlin Shao²

¹Department of Microbiology, Immunology & Molecular Genetics, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229.

Proceedings of the National Academy of Sciences of the United States of America

|February 7, 2019

Summary

Chromosome organization in malaria parasites is linked to virulence gene expression. Spatial genome arrangements, especially virulence gene clustering, vary across Plasmodium species, influencing gene silencing and nuclear structure.

Keywords:

Hi-C epigenomics genome organization malaria virulence

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Area of Science:

Genomics and Molecular Biology
Parasitology
Cell Biology

Background:

Eukaryotic chromosome positioning is organized and dynamically linked to gene expression.
In Plasmodium falciparum, virulence gene clustering correlates with gene silencing and genome organization.

Purpose of the Study:

To identify conserved and species-specific principles of genome organization in Plasmodium and related parasites.
To investigate the relationship between 3D genome structure, virulence genes, and gene expression.

Main Methods:

Performed Hi-C experiments to capture genome-wide interactions.
Generated 3D genome models for seven different species (five Plasmodium, two related apicomplexans).
Analyzed chromosome clustering patterns, including centromeres, telomeres, and virulence genes.

Main Results:

Plasmodium species predominantly exhibit clustering of centromeres, telomeres, and virulence genes.
The repressive effect of virulence gene clusters on nuclear space varies across species (strongest in P. falciparum, absent in P. yoelii).
P. knowlesi shows dispersed telomeres and virulence genes but strong correlation between 3D genome and gene expression.
Babesia microti displays Rabl organization with subtelomeric virulence gene colocalization; Toxoplasma gondii shows centromere clustering without virulence gene clustering.

Conclusions:

Spatial genome organization in most Plasmodium species is constrained by virulence gene colocalization.
Unique effects of virulence genes on chromosome folding in P. falciparum and P. knowlesi suggest a link to gene expression and pathogenicity.