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Genetic changes during laboratory propagation: copy number At the reticulocyte-binding protein 1 locus of Plasmodium
Shalini Nair1, Standwell Nkhoma, François Nosten
1Southwest Foundation for Biomedical Research (SFBR), San Antonio, TX, USA.
Abstract:
Comparative genomic hybridization studies have revealed elevated copy number (CN) at the reticulocyte-binding protein 1 gene (PfRh1) in fast growing lab-adapted parasites, while genetic manipulation demonstrates a causal link between cell invasion and PfRh1 CN. We therefore examined PfRh1 copy number variation (CNV) in 202 single clone parasite isolates from four countries to quantify the extent of CNV within natural populations. Surprisingly, we found that no natural parasite infections showed elevated CN. In contrast, 4/28 independent laboratory reference strains show elevated CN. One possibility is that amplification of PfRh1 (or neighboring loci) is selected during laboratory culture. In the case of FCR3 group of parasites, clone trees show that PfRh1 amplification arose in laboratory lines following establishment in culture. These data show that CNV at PfRh1 is rare or non-existent in natural populations, but can arise during laboratory propagation. We conclude that PfRh1 CNV is not an important determinant of gene expression, cell invasion or growth rate in natural parasite populations.
Insights
Reticulocyte-binding protein 1 gene copy number variation is absent in natural parasite populations. Amplification of this gene occurs during laboratory culture, not in the wild, suggesting it does not impact parasite growth or invasion in nature.
Area of Science:
- Genomics
- Parasitology
- Molecular Biology
Background:
- Comparative genomic hybridization identified increased reticulocyte-binding protein 1 (PfRh1) gene copy number (CN) in fast-growing laboratory-adapted parasites.
- Genetic manipulation studies indicated a direct relationship between cell invasion efficiency and PfRh1 CN.
Purpose of the Study:
- To investigate the prevalence and extent of PfRh1 copy number variation (CNV) in natural parasite populations.
- To determine if PfRh1 CNV is a significant factor in parasite growth and invasion rates in natural settings.
Main Methods:
- Analysis of PfRh1 CNV in 202 single-clone parasite isolates collected from four different countries.
- Comparative genomic hybridization and clone tree analysis were employed.
Main Results:
- No instances of elevated PfRh1 CN were detected in any of the natural parasite isolates examined.
- In contrast, 4 out of 28 independent laboratory reference strains exhibited elevated PfRh1 CN.
- Evidence suggests PfRh1 amplification in certain laboratory parasite lines (FCR3 group) occurred post-establishment in culture.
Conclusions:
- PfRh1 CNV is rare or absent in natural parasite populations.
- Gene amplification at the PfRh1 locus appears to be a phenomenon selected for during laboratory cultivation, not a trait prevalent in natural infections.
- PfRh1 CNV is unlikely to be a key determinant of gene expression, cell invasion, or growth rate in natural parasite populations.
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