Plasmodium falciparumthe malaria parasite, alters its genes through an evolutionary “copy-and-paste” tactic, making it difficult to kill
Which animal kills the most people every year? Sharks, tigers, snakes? None of that. This is the mosquito whose bite transmits a simple microscopic parasite, the Plasmodium falciparumwhat causes malaria.
According to the latest global malaria report, there will be an estimated 249 million malaria cases and more than 600,000 deaths from the disease worldwide in 2022. 94% of malaria cases and 95% of deaths from the disease are recorded in Africa, where infants, pregnant women, travelers and people with HIV/AIDS are most at risk. Up to 249 million people died there in 2022.
Why don’t we have an effective vaccine against malaria yet?
The reason lies in the complexity of the parasite Plasmodiumwhich goes through multiple phases in its life cycle, making it difficult to effectively target all phases with a single vaccine.
The parasite PlasmodiumIn addition, it has a large genetic variability in its surface proteins, which allows it to evade the host’s immune system. It could be helpful to know the mechanism by which these genes change, and that is exactly what has now been achieved.
By analyzing the genetic diversity of the deadliest human malaria parasite Plasmodium falciparumResearchers at the EMBL European Bioinformatics Institute (EMBL-EBI) have identified a genetic “copy-paste” mechanism that rapidly increases the parasite’s genetic diversity. This helps solve a long-standing mystery as to why the parasite has so much genetic diversity.
The new study, published in the journal PLOS Biology, provides important data on the evolutionary history of P. falciparum by analyzing two genes that encode surface proteins essential for immune evasion. The genes in question are DBLMSP and DBLMSP2.
These findings deepen our understanding of how the malaria parasite evolved and could help inform new approaches to vaccine development, offering hope for more effective prevention methods against a disease that continues to affect millions of people around the world.
Copy and paste genetics
Typically, an individual’s genetic sequence is inherited from its parents, but under certain circumstances, part of a genetic sequence can be copied between different genes on the same DNA molecule, called non-allelic genetic conversion. This process is associated with the evolution of important gene families, including those involved in the function of the human immune system.
One of the key findings of this study is that gene conversion occurs between the DBLMSP and DBLMSP2 genes P. falciparum and results in greater genetic diversity within the parasite’s surface proteins. Because these proteins are exposed to and interact with our immune system, they are potential targets for vaccines, and a more comprehensive understanding of their genetic diversity could be very valuable for vaccine development.
“The discovery of ‘copy-paste’ genetics in malaria DNA highlights the implications of an underestimated evolutionary mechanism,” said Brice Letcher, postdoctoral researcher at the Laboratory of Cell Biology and Modeling (LBMC, France) and former graduate student at EMBL -EBI. “Here we show that genetic conversion was a potentially important strategy in the ability of malaria to adapt and thrive in humans, perhaps even to evade the human immune system.” Understanding this genetic flexibility offers new insights into the persistence of malaria Malaria and its adaptation to the human host.”
Map of hidden genetic diversity in malaria parasites
Any protein that interacts with the immune system is potentially a target for vaccine development, but knowledge of global genetic diversity is an important requirement without which no progress is possible.
For example, vaccines against influenza and SARS-CoV-2, which cause COVID-19, are being developed based on insights into the evolution of their genomes. The unusual genetic diversity of the DBLMSP and DBLMSP2 genes P. falciparum They are so extreme that current algorithms for mapping genetic variants cannot capture them, so researchers don’t know much about the variation in these genes.
To solve this problem, researchers developed new bioinformatics software that uses genomic diagrams and analyzed a large sample of parasites from 29 countries. This new approach revealed a large number of previously hidden variants and was able to demonstrate that multiple gene conversion events had occurred. These new variants, which can be downloaded from the website linked to the study, represent a valuable resource for the malaria research community.
“Genomic diagrams are an excellent method of bioinformatics that help us decipher the complex genetic landscapes that arise from the interaction between pathogens and human hosts,” said Sorina Maciuca, co-author and former graduate student in Iqbal’s group and genomic data scientist at Genomics . England. “They allow us to consider a broader range of genetic diversity and gain new insights into how pathogens such as: P. falciparum and escape our immune system.
What are genomic diagrams?
The traditional approach in genomics is to define a reference genome and describe every other genome as a series of small differences from that reference. This doesn’t work well if the genomes differ too much. Genomic diagrams take a population of genomes and create a reference set that knows all of the species’ genetic variations.
“This research provides a complete map of the genetic diversity of these two fascinating genes P. falciparum“said Zamin Iqbal, group leader at EMBL-EBI and professor of algorithmic and microbial genomics at the University of Bath. “We have been trying to understand the unusual patterns of these genes for almost a decade, and our best hypothesis was that, for reasons unknown, really different ‘versions’ of the gene were maintained by natural selection.” Here we have shown that this copying mechanism – gene conversion – has indeed repeatedly created these different abnormal “versions” of genes. “These data not only improve our understanding of the biology of malaria , but will also be valuable to researchers around the world studying these genes and their interaction with our immune system.”
REFERENCE
Role of gene conversion in the development of cell surface antigens of the malaria parasite Plasmodium falciparum
Image: The malaria parasite creates genetic diversity through an evolutionary “copy-and-paste” tactic. Photo credit: Karen Arnott/EMBL-EBI, Isabel Romero Calvo/EMBL