Long thought to only cause a rare disease, this mutation may ward off malaria

March 22, 2018, The Scripps Research Institute
Credit: CDC

A genetic mutation that may protect people from malaria, but was thought to be rare, is surprisingly common, suggest the findings of a new study led by scientists at The Scripps Research Institute (TSRI). The discovery sheds light on how humans who live in close quarters with malaria-carrying mosquitos may evolve defenses against the disease.

The researchers found that a mutation in the gene PIEZO1, which codes for a pressure-sensing protein, can dehydrate red blood cells. In a mouse model, this mutation made it harder for the parasite Plasmodium to infect red blood and cause cerebral malaria (a severe neurological complication of Plasmodium infection). This red blood cell dehydration condition, called hereditary xerocytosis, was thought to be extremely rare, so the researchers were surprised to find it could be present in one in three people of African descent.

"This syndrome is not rare anymore," says Shang Ma, PhD, a research associate at TSRI and first author of the study, published March 22, 2018 in the journal Cell. The study was led by Ardem Patapoutian, PhD, a professor at TSRI and a Howard Hughes Medical Institute investigator.

The mutation in PIEZO1 is uncommon in non-African populations and had never been the focus of a large-scale analysis. The new findings suggest the mutation is much more common in areas where people have lived alongside selection pressure from malaria.

"This study is a good example of a host/pathogen arms race playing out in real-time—this time with the host a likely winner," says Kristian Andersen, PhD, an assistant professor at TSRI and director of Infectious Disease Genomics at the Scripps Translational Science Institute (STSI).

The PIEZO1 mutation is not the first adaptation linked to malaria resistance. People of African descent are also more likely to have a genetic condition called sickle cell disease, which makes it harder for Plasmodium to enter their . Going forward, Andersen says, large-scale genomic association studies will be needed to confirm the PIEZO1 mutation's role in malaria resistance.

Patapoutian says his lab plans to learn more about the biological role of PIEZO1 and how in the protein could affect other health conditions. "The fact that we have a will make it seamless to test mechanisms behind any association we find in humans," says Patapoutian. Indeed, PIEZO1 as a pressure sensor is important for cardiovascular development and function, and its deletion is proposed to cause hypertension.

Explore further: Researchers get first complete look at protein behind sense of touch

More information: "Common PIEZO1 allele in African populations causes RBC dehydration and attenuates Plasmodium infection," Cell (2018).

Related Stories

How cells protect themselves against mechanical stress

March 15, 2018

The Piezo1 and Piezo2 ion channels are known to open up response to the slightest mechanical stimulus. MDC researchers have now discovered that the channels are also sensitive to changes in membrane voltage. The voltage sensitivity ...

Scientists find new antimalarial drug targets

February 20, 2018

Researchers have discovered crucial new processes that allow malaria parasites to escape red blood cells and infect other cells, offering potential new treatment targets. The team are already working with pharmaceutical companies ...

Researchers identify defense mechanism of malaria parasite

November 7, 2017

Portuguese researchers at Instituto de Medicina Molecular (iMM) Lisboa have identified a defense mechanism by which the Plasmodium parasite can survive inside its host's liver cells, a crucial stage in which it acquires the ...

Recommended for you

Staying a step ahead of the game

October 18, 2018

Trypanosoma brucei, which causes sleeping sickness, evades the immune system by repeatedly altering the structure of its surface coat. Sequencing of its genome and studies of its 3-D genome architecture have now revealed ...

Elucidating cuttlefish camouflage

October 18, 2018

The unique ability of cuttlefish, squid and octopuses to hide by imitating the colors and texture of their environment has fascinated natural scientists since the time of Aristotle. Uniquely among all animals, these mollusks ...

Biodiversity can also destabilize ecosystems

October 18, 2018

Ecosystems have a variety of benefits to humans, including food, water and other resources, as well as recreational space. It is therefore important that these systems remain functional and stable—especially in view of ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.