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From climate change to mind control, protists run the world

You may never have heard of them but protists have the power to make or break life on Earth. From mind-controlling parasites to oxygen-belching phytoplankton, these single-celled organisms dominate the tree of life - yet we know precious little about them.

November 13, 2020

You may never have heard of them but protists have the power to make or break life on Earth. From mind-controlling parasites to oxygen-belching phytoplankton, these single-celled organisms dominate the tree of life - yet we know precious little about them.

The Earlham Institute’s Hall Group is one of the few labs studying these complex creatures and documenting their genomes as part of the Darwin Tree of Life Project. What they discover from the humble protists could have global ramifications.

“If you understand the biology of protists, you can understand all of the different methods life employs to exist on Earth,” says Professor Neil Hall, Director of the Earlham Institute.

“Protists are so diverse. In their cell biology, their genetic code and the environments they live in.”

Twenty years ago, Professor Hall turned his hand from studying fungal pathogens to sequencing the genome of Plasmodium falciparum, the parasite which causes malaria. It was the first protist ever to have its genome sequenced, and he has never looked back.

“It’s a very cool protist to study, but definitely not to have,” says Hall, as he recounts the quite remarkable adaptations shown by one of the most pernicious, and prominent, protist species of them all.

“It has an amazing life cycle. After a mosquito bite, sporozoites enter the blood and will find your liver within minutes. In the liver, they develop into merozoites which then target your red blood cells, as well as various sexually reproducing forms which exist in the blood. There are yet more forms which are well adapted to live within the mosquito, after being picked up following a fresh bite, where they eventually develop once again into the sporozoites that will go on to infect another person.

“All this for an organism with a small genome of just 23 million base pairs and 5000 genes [for comparison, the average bacterial genome is about ten times smaller with a similar number of genes (give or take a few thousand), while the human genome is more than ten times larger with around 20,000 or so genes].”

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If you understand the biology of protists, you can understand all of the different methods life employs to exist on Earth.

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Single-celled flagellate Eukaryote Euglena under the microscope

Image: Single-celled flagellate Eukaryote Euglena under the microscope

Parasites

When we speak of protists, it’s often in the same breath as the word parasites. “That’s the story you find throughout the history of what we’ve discovered and when,” says Dr Ross Low, a postdoctoral scientist working in the Neil Hall Group. “The things that cause human disease, generally speaking, have been very well studied - including protists.”

Low works on several parasites which cause a variety of chronic and deadly conditions, from African sleeping sickness in people to frounce in birds. Like the malaria parasite, they have some remarkable adaptations to a life infecting an animal host.

Trypanosomes, for example, have a really interesting method for escaping the immune system,” says Low, who has been investigating the novel genomics of these persistent parasites. “The outside of the cell is covered with a protective coat, which hides all of the proteins the immune system would normally target. Every time the immune system mounts a defence to this coat, it’ll change the coat. So you can have these persistent infections which can last 60 plus years - potentially the entire lifetime of the host.”

In fact, protists harbour a range of exotic strategies to trick their animal hosts.

The malaria parasite, as well as employing a similarly devious cloaking tactic as trypanosomes, also appears to induce fevers in people as a mechanism to produce more sweat. As the malaria-transmitting mosquitoes are attracted to human sweat, this increases the chance of a mosquito being able to pass on the parasite to the next person.

Toxoplasma gondii, a parasite of cats, employs a particularly wild strategy of mental manipulation.

“It’s not an unusual concept that parasites often change the behavior of their hosts or somehow help the parasite to be passed on,” says Professor Hall. “The story goes that Toxoplasma gondii has a primary host, which is a cat, but it’s excreted in the faeces of the cat, to then be taken up by other organisms in the environment including rodents.

“It’s thought that it makes a mouse or a rat less risk averse, and therefore more likely to be eaten by a cat, so that the parasite can complete its life cycle.”

This mind-controlling parasite doesn’t just play with cat and mouse. Terrifyingly, it’s estimated that a third of the global human population have been infected, although any affect on behaviour or risk-taking is so far unknown.

Mosquitoes are carriers of the malaria parasite - Plasmodium falciparum

Why genomics is important

Parasites are bad news, made even worse by the fact they are very hard to treat. Some diseases, such as leishmaniasis - caused by a flesh eating protist - require treatment with the heavy doses of radiation or chemotherapy normally reserved for systemic cancers.

“One of the challenges of treating protist diseases, as opposed to bacteria, is that protists are eukaryotes like us and therefore have a lot more similar pathways,” says Hall.

This common ground is one of the main reasons the Hall Group is trying to decode the genomes of these parasites.

“The weirdest parasite I study is probably trichomonas” says Low, “which causes a sexually transmitted disease in humans. In birds, it causes their throat to swell up so they can’t eat or drink.

“Other variants cause abortions in cattle, which leads to a big loss of money for beef and dairy farms. They’re important economically, especially in the developing world, where the loss of a calf might significantly impact your income.

“If you know the genome, however, then you can start to build weapons and vaccines against trichomonas, which you can use to protect the population, or your farm.”

This approach has been demonstrated in Plasmodium falciparum, explains Professor Hall. “The genome was sequenced 20 years ago and already you can see things like subunit vaccines, which were based around antigen sequences discovered in the genome, and drugs used to target metabolic pathways identified from genomic data. You can see the results of that coming through.”

Greenfinches are particularly susceptible to the parasite Trichomonas gallinae which causes their throat to swell up so they can’t eat or drink

Image: A greenfinch which is susceptible to the parasite Trichomonas gallinae
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If you take every animal you can think of, that’s one branch on the tree of life. All of the plants - from mosses and some types of seaweed to trees - that’s another. All of the fungi comprise a third. At the same sort of level among the protists, there’s probably about 80 branches – each containing as much, if not more, diversity as any one of the others.

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A complex web of life

Considering the fact that almost every animal species harbours potentially dozens of parasites, there are likely to be many millions of species of those alone among the protists. Among the millions of others are plenty of free-living creatures from which we can learn a whole lot more. Take Euglena gracilis, for instance.

“Euglena is like a free-living version of the trypanosomes which Ross is studying,” says Dr ThankGod Ebenezer, who recently moved to the European Bioinformatics Institute (EMBL-EBI) after working for several years in the Haerty Group at EI.

“You can understand the evolution of how something becomes a parasite by looking at Euglena and comparing it to trypanosomes.”

Ebenezer spent his PhD sequencing the complex genome of Euglena, a complicated organism that can photosynthesise like a plant but is totally unrelated to either plants or animals. Photosynthesising protists such as Euglena, rather than trees (which are still crucial), truly deserve the accolade of “lungs of the Earth”. Along with algae such as coccolithophores and diatoms, they produce somewhere in the region of two thirds of all the oxygen we breathe.

The full genome sequence of Euglena comes in at an estimated two billion base pairs - a lot closer in size to the human genome than that of malaria, which is ten times smaller. That difference alone alludes to the somewhat ridiculous nature of grouping all of these diverse organisms under one taxonomic banner.

“If you take every animal you can think of” says Low, “that’s one branch on the tree of life. All of the plants - from mosses and some types of seaweed to trees - that’s another. All of the fungi comprise a third.

“At the same sort of taxonomic level among the protists, there’s probably about 80 branches – each containing as much, if not more, diversity as any one of the others.”

That diversity is what makes protists particularly fascinating, as they’re found in every sort of environment imaginable - from freezing Antarctic waters to the biofilms lining the human gut. That’s why the Darwin Tree of Life Project (DToL) offers a tantalising opportunity to discover unimaginable amounts of new information about life on Earth.

Euglena, a complicated organism that can photosynthesise like a plant but is totally unrelated to either plants or animals

Sampling the Tree of Life

DToL is part of a larger global endeavour to sequence the genomes of all eukaryotic life on Earth. That means mapping out the entire DNA sequence for every animal, plant, fungus and protist.

Professor Hall suggests that it’s only by sampling the tree of life in this way that we will finally be able to answer the important question of what genes really do.

“Because protists are so diverse, you can look at all branches on the tree of life and ask ‘ok, where do we see photosynthesis and what genes do we associate with that’,” he explains. “Some protists have lost their mitochondria. You can ask ‘ok, they’ve lost those, what else have they lost, what genes don’t they need’?

“Once we’ve sampled all of the tree of life, we can start to see what genes always co-occur with each other and how that relates to structures in the cells we see, or what metabolic pathways they are associated with.

“The only way you can really do that is by really deep sampling of biodiversity.”

It’s a massive task but the dividends could be equally huge.

“There are all sorts of examples in protists,” says Hall. “RNA editing was discovered in trypanosomes. No one thought by looking at an organism that was 2 billion years diverged from animals that you would learn something about animal life, but there are many examples like that.”

Low shares the same excitement for the diverse applications that could arise from this project. “We know so little about so many protists that are out there,” he says. “But in most cases, nobody has looked yet.”

Protists are challenging to collect, isolate and generate reliable genetic data from. The Hall Group are unperturbed by these challenges and are instead motivated by the unknown potential benefits from studying these organisms.

“It’s a bit like saying to Darwin ‘what do you hope to discover by collecting all those finches?’” explains Professor Hall.

“He didn’t set out to discover speciation. He collected samples and analysed the data when he got back to Down house. Part of it is generating data so that you can generate a theory, and then test that theory.

“There’s all sorts of things that we don’t know, but we have a fantastic opportunity to find out.”

Peter Bickerton

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Peter Bickerton

Scientific Communications & Outreach Manager