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Photo courtesy of
Sesh Sundararaman,
University of Pennsylvania
By studying malaria parasites found in chimpanzees, researchers believe they have gained new insights regarding a malaria parasite that infects humans.
The team used a selective amplification technique to sequence the genomes of 2 divergent Plasmodium species, P reichenowi and P gaboni, from chimpanzee blood.
This revealed clues about the evolution and pathogenicity of P falciparum, the deadliest malaria parasite that affects humans.
The researchers described this work in Nature Communications.
They noted that African apes harbor at least 6 Plasmodium species that have been classified into a separate subgenus, called Laverania. Three of these Laverania species, including P reichenowi and P gaboni, reside in chimps.
Three others—including P praefalciparum, which gave rise to P falciparum—reside in gorillas. The gorilla origin of P falciparum was discovered several years ago by this same group of investigators.
“We want to know why Plasmodium falciparum is so deadly,” said Beatrice Hahn, MD, of the University of Pennsylvania in Philadelphia.
“The answer must lie in the blueprint—the genome—of its chimpanzee and gorilla cousins. We also want to know how and when the gorilla precursor of Plasmodium falciparum jumped into humans and why this happened only once.”
In an attempt to answer these questions, Dr Hahn and her colleagues used their selective amplification method to sequence Laverania genomes.
They used small amounts of unprocessed blood collected during routine health screens of chimpanzees living in sanctuaries. With their technique, the team found they could generate “high-quality” Laverania genome sequences.
The researchers said the chimpanzee parasite genomes contain information about the evolutionary origins of the malaria parasites infecting humans. One of the first things to emerge from genome-wide analyses was that the parasites represent distinct, non-interbreeding species.
In addition, members of each chimpanzee parasite species display about 10 times more genetic diversity than human parasites.
“The chimpanzee parasites really highlight the lack of diversity in Plasmodium falciparum,” said Paul Sharp, PhD, of the University of Edinburgh in the UK.
“This is most likely because these parasites went through a severe bottleneck when first transmitted to humans, perhaps within the past 10,000 years.”
By comparing the different parasite genomes, the researchers found an expansion of a multi-gene family, which governs red blood cell remodeling and therefore helps the parasite to evade host immune cells and clearance by the spleen.
“The remodeling process is a key part of severe malaria pathology in human Plasmodium falciparum infections,” said Julian Rayner, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK.
“The expansion of this gene family from a single gene in all other Plasmodium parasites to up to 21 genes in Laverania suggests that remodeling evolved early in the radiation of this group of primate parasites and contributed not only to their unique biology but perhaps also to their successful expansion.”
“We also found a short region of the genome, including 2 essential invasion genes, where Plasmodium falciparum was much more different from its close relatives than we expected,” said Lindsey Plenderleith, PhD, of the University of Edinburgh.
Further analysis yielded the surprising finding that this fragment of DNA was horizontally transferred—from one species to another—into the gorilla ancestor of P falciparum.
“It is tempting to speculate that this unusual event somehow predisposed the precursor of Plasmodium falciparum to colonize humans,” Dr Hahn said. “However, this gene transfer clearly is not the entire story.”
Although the origin of P falciparum is considered well-established, nothing is known about the circumstances that led to its emergence.
“Coaxing entire parasite genome sequences out of small quantities of unprocessed ape blood will help us to better understand what happened and whether it can happen again,” said Sesh Sundararaman, an MD/PhD student at the University of Pennsylvania.
The team plans, as a next step, to use their select genome amplification technique to sequence additional ape parasite genomes to identify host-specific interactions and transmission requirements. They believe this would reveal vulnerabilities that might be exploited to combat malaria in humans.
Photo courtesy of
Sesh Sundararaman,
University of Pennsylvania
By studying malaria parasites found in chimpanzees, researchers believe they have gained new insights regarding a malaria parasite that infects humans.
The team used a selective amplification technique to sequence the genomes of 2 divergent Plasmodium species, P reichenowi and P gaboni, from chimpanzee blood.
This revealed clues about the evolution and pathogenicity of P falciparum, the deadliest malaria parasite that affects humans.
The researchers described this work in Nature Communications.
They noted that African apes harbor at least 6 Plasmodium species that have been classified into a separate subgenus, called Laverania. Three of these Laverania species, including P reichenowi and P gaboni, reside in chimps.
Three others—including P praefalciparum, which gave rise to P falciparum—reside in gorillas. The gorilla origin of P falciparum was discovered several years ago by this same group of investigators.
“We want to know why Plasmodium falciparum is so deadly,” said Beatrice Hahn, MD, of the University of Pennsylvania in Philadelphia.
“The answer must lie in the blueprint—the genome—of its chimpanzee and gorilla cousins. We also want to know how and when the gorilla precursor of Plasmodium falciparum jumped into humans and why this happened only once.”
In an attempt to answer these questions, Dr Hahn and her colleagues used their selective amplification method to sequence Laverania genomes.
They used small amounts of unprocessed blood collected during routine health screens of chimpanzees living in sanctuaries. With their technique, the team found they could generate “high-quality” Laverania genome sequences.
The researchers said the chimpanzee parasite genomes contain information about the evolutionary origins of the malaria parasites infecting humans. One of the first things to emerge from genome-wide analyses was that the parasites represent distinct, non-interbreeding species.
In addition, members of each chimpanzee parasite species display about 10 times more genetic diversity than human parasites.
“The chimpanzee parasites really highlight the lack of diversity in Plasmodium falciparum,” said Paul Sharp, PhD, of the University of Edinburgh in the UK.
“This is most likely because these parasites went through a severe bottleneck when first transmitted to humans, perhaps within the past 10,000 years.”
By comparing the different parasite genomes, the researchers found an expansion of a multi-gene family, which governs red blood cell remodeling and therefore helps the parasite to evade host immune cells and clearance by the spleen.
“The remodeling process is a key part of severe malaria pathology in human Plasmodium falciparum infections,” said Julian Rayner, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK.
“The expansion of this gene family from a single gene in all other Plasmodium parasites to up to 21 genes in Laverania suggests that remodeling evolved early in the radiation of this group of primate parasites and contributed not only to their unique biology but perhaps also to their successful expansion.”
“We also found a short region of the genome, including 2 essential invasion genes, where Plasmodium falciparum was much more different from its close relatives than we expected,” said Lindsey Plenderleith, PhD, of the University of Edinburgh.
Further analysis yielded the surprising finding that this fragment of DNA was horizontally transferred—from one species to another—into the gorilla ancestor of P falciparum.
“It is tempting to speculate that this unusual event somehow predisposed the precursor of Plasmodium falciparum to colonize humans,” Dr Hahn said. “However, this gene transfer clearly is not the entire story.”
Although the origin of P falciparum is considered well-established, nothing is known about the circumstances that led to its emergence.
“Coaxing entire parasite genome sequences out of small quantities of unprocessed ape blood will help us to better understand what happened and whether it can happen again,” said Sesh Sundararaman, an MD/PhD student at the University of Pennsylvania.
The team plans, as a next step, to use their select genome amplification technique to sequence additional ape parasite genomes to identify host-specific interactions and transmission requirements. They believe this would reveal vulnerabilities that might be exploited to combat malaria in humans.
Photo courtesy of
Sesh Sundararaman,
University of Pennsylvania
By studying malaria parasites found in chimpanzees, researchers believe they have gained new insights regarding a malaria parasite that infects humans.
The team used a selective amplification technique to sequence the genomes of 2 divergent Plasmodium species, P reichenowi and P gaboni, from chimpanzee blood.
This revealed clues about the evolution and pathogenicity of P falciparum, the deadliest malaria parasite that affects humans.
The researchers described this work in Nature Communications.
They noted that African apes harbor at least 6 Plasmodium species that have been classified into a separate subgenus, called Laverania. Three of these Laverania species, including P reichenowi and P gaboni, reside in chimps.
Three others—including P praefalciparum, which gave rise to P falciparum—reside in gorillas. The gorilla origin of P falciparum was discovered several years ago by this same group of investigators.
“We want to know why Plasmodium falciparum is so deadly,” said Beatrice Hahn, MD, of the University of Pennsylvania in Philadelphia.
“The answer must lie in the blueprint—the genome—of its chimpanzee and gorilla cousins. We also want to know how and when the gorilla precursor of Plasmodium falciparum jumped into humans and why this happened only once.”
In an attempt to answer these questions, Dr Hahn and her colleagues used their selective amplification method to sequence Laverania genomes.
They used small amounts of unprocessed blood collected during routine health screens of chimpanzees living in sanctuaries. With their technique, the team found they could generate “high-quality” Laverania genome sequences.
The researchers said the chimpanzee parasite genomes contain information about the evolutionary origins of the malaria parasites infecting humans. One of the first things to emerge from genome-wide analyses was that the parasites represent distinct, non-interbreeding species.
In addition, members of each chimpanzee parasite species display about 10 times more genetic diversity than human parasites.
“The chimpanzee parasites really highlight the lack of diversity in Plasmodium falciparum,” said Paul Sharp, PhD, of the University of Edinburgh in the UK.
“This is most likely because these parasites went through a severe bottleneck when first transmitted to humans, perhaps within the past 10,000 years.”
By comparing the different parasite genomes, the researchers found an expansion of a multi-gene family, which governs red blood cell remodeling and therefore helps the parasite to evade host immune cells and clearance by the spleen.
“The remodeling process is a key part of severe malaria pathology in human Plasmodium falciparum infections,” said Julian Rayner, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK.
“The expansion of this gene family from a single gene in all other Plasmodium parasites to up to 21 genes in Laverania suggests that remodeling evolved early in the radiation of this group of primate parasites and contributed not only to their unique biology but perhaps also to their successful expansion.”
“We also found a short region of the genome, including 2 essential invasion genes, where Plasmodium falciparum was much more different from its close relatives than we expected,” said Lindsey Plenderleith, PhD, of the University of Edinburgh.
Further analysis yielded the surprising finding that this fragment of DNA was horizontally transferred—from one species to another—into the gorilla ancestor of P falciparum.
“It is tempting to speculate that this unusual event somehow predisposed the precursor of Plasmodium falciparum to colonize humans,” Dr Hahn said. “However, this gene transfer clearly is not the entire story.”
Although the origin of P falciparum is considered well-established, nothing is known about the circumstances that led to its emergence.
“Coaxing entire parasite genome sequences out of small quantities of unprocessed ape blood will help us to better understand what happened and whether it can happen again,” said Sesh Sundararaman, an MD/PhD student at the University of Pennsylvania.
The team plans, as a next step, to use their select genome amplification technique to sequence additional ape parasite genomes to identify host-specific interactions and transmission requirements. They believe this would reveal vulnerabilities that might be exploited to combat malaria in humans.