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Biology's Dark Matter - the unseen life with a huge impact

Animals, plants and fungi are mere branches among the thousands that branch off the tree of life. At EI, we’re exploring the less explored of those boughs, where the vast diversity of life exists - among the protists.

16 September 2019

When we think of life, it is most often the plants, animals and fungi that live visibly among and around us, perhaps the charismatic species broadcast on Planet Earth or the exotic fauna in zoos. But animals, plants and fungi are mere branches among the thousands that branch off the tree of life. At EI, we’re exploring the less explored of those boughs, where the vast diversity of life exists - among the protists.

Potato blight, red tides, malaria, leishmaniasis: what do all of these have in common? They’re all caused by protists, single celled eukaryotes (organisms with a nucleus and other cellular compartments packaged in a membrane), and that’s where the similarities end.

The word protist, unlike animal or plant, does not refer to a single ‘group’ of organisms on the tree of life, but a whole range of lifeforms. Some of them we’d call algae, others perhaps slime moulds, water moulds, amoebas. These are all single celled eukaryotes (most of the time), which belong to various different branches of the tree.

Some, such as the amoeba, are much more like animals than plants. Others, such as the chlorophyta (green algae such as Chlamydomonas), are much more like plants than animals. However, it’s not massively clear cut. Many among the green algae, for example, have an eyespot which contains proteins related to those in our own eyes, which they use to detect light.

Even making comparisons with animals and plants in this context is almost meaningless, considering that these are just two miniscule branches among hundreds in the tree of life. If you think of the millions of species of animals and plants around you and consider that this diversity sits within just two branches, imagine how much diversity there is still to discover.

Here at EI, we are part of the Darwin Tree of Life project that aims to understand what Director Neil Hall describes as “Biology’s Dark Matter”.

 

Talk: Decoding Nature's Dark Matter

Come and see our Director Neil Hall on the Norwich Research Park day at the Norwich Science Festival where, along with EI’s amazing BEE TRAIL, he will be giving a fascinating talk on “Decoding Nature's Dark Matter”.
 

Why study protists?

What we know about protists mostly stems from the fact that they are common parasites and cause some of the most deadly diseases on Earth. Malaria, the most prominent, kills millions of people in tropical regions annually. Other well known diseases caused by protists include African sleeping sickness, leishmaniasis and Chagas disease.

African sleeping sickness and Chagas disease are both caused by Trypanosomes, which Ross Low of the Hall Group at EI is interested in for reasons other than how devastatingly awful they are. These protists belong to the Kinetoplastid group, which are evolutionarily bizarre.

They’re not bizarre because of what they look like, like the real-life protist Kraken, Kraken carinae (I dare you to look it up, it’s actually called that). They’re bizarre because of their unique genetics and how their genes are expressed in large blocks, in what’s known as ‘polycistronic expression’.

I had to have this explained to me in simple terms. Essentially, however, genes tend to be expressed when they’re needed (not always, but often), and are “turned on” or “turned off” in different places and at different times, especially in eukaryotes like us. This happens before the genes are transcribed by cells (most of the time).

Kinetoplastids, however, have highly conserved genes present in big blocks that are all transcribed whether they’re needed or not. The regulation of these genes then happens after they’ve been read rather than before.

This is so weird for eukaryotes that it is thought that this might be a very primitive form of gene expression, especially as this is more like how bacteria express genes, which exist as ‘operons’ - conjoined blocks of DNA that code for whole processes.

Polycistronic expression is weird, but it’s also very useful for studying evolution, as the blocks of genes can be highly conserved. This means that it’s relatively easy, if we know what blocks of genes are present in related species, to spot where one is missing. In this way we are able to look at the differences and ask how these came to be in different conditions.

One such interesting question, for example, is how trypanosomes came to be parasitic, compared to a close relative, Bodo saltans, which lives freely. It’s also interesting to compare parasites with non-parasites, as the former sometimes appear to have lost metabolic pathways, such as sugar metabolism, after their long history living within their hosts, who now do much of the work for them.

 

An illustration of the Trypanosoma cruzi parasite in the bloodstream, which causes Chagas disease (American trypanosomiasis), a severe infection and inflammation of body tissues, commonly in the heart and the intestinal tract.
Biology Dark Matter unseen life protists trypanosoma cruzi parasite 770

They’re not bizarre because of what they look like, like the real-life protist Kraken... ...they’re bizarre because of their unique genetics and how their genes are expressed in large blocks, in what’s known as ‘polycistronic expression’.

Careful with that axe, Euglena!

Another non-parasitic relative of trypanosomes that Ross is studying is called euglena, which is a very interesting protist indeed.

Not content with having a chloroplast that allows it to use sunlight to make sugar (along with a pyrenoid that makes it extra-efficient at photosynthesis), euglena can also gobble up other green algae, amoebas, parameciums and rotifers (the latter are actually miniscule but multicellular creatures).

Due to its capacity to photosynthesise, euglena is a good candidate for producing renewable biofuels, which provides a decent economical reason to investigate it in more detail. From an evolutionary perspective, too, it’s a fantastic candidate to study. For a start, for such a tiny cell, it has a big genome which has proved very difficult to sequence.

Coming in at about 2 billion base pairs of DNA sequence, the euglena genome is about two-thirds the size of our own. To add complexity into the mix, however, euglena is triploid (rather than diploid like us) and its genome contains lots of repeat elements that make it really hard to assemble.

However, we like a challenge at EI, and we’re very adept at decoding complex, non-human genomes. As such, Ross will be using the latest pipeline developed by the Clavijo group to sequence and assemble the euglena genome as part of our “anniversary genomes” project.

The aim of the project is to sequence and assemble complex genomes from across the tree of life, with euglena forming the case study for protists, joining other hard-to-decode plant and animal genomes including Nicotiana benthamiana, red clover, the East African soda cichlid and the strawberry.

 

About 2 billion base pairs of DNA sequence, the euglena genome is about two-thirds the size of our own. To add complexity into the mix, however, euglena is triploid (rather than diploid like us) and its genome contains lots of repeat elements that make it really hard to assemble.

Darwin tree of life

The work won’t stop there.

We are part of the Darwin Tree of Life project that aims to sequence all of the protists in the UK. That is no mean feat, as protists aren’t as easy to sample as some of the more flashy, larger wildlife such as mammals, birds, insects or trees.

We’re going to have to find our protists in the soil, in lakes and ponds, and in the microbiomes of other organisms, and then separate the cells so that we know what we’re looking at. It’s likely that, along with the many species we already know about, we’re going to find a whole host more that we have never come across.

Thankfully, we have expertise at EI not only in protists but also single cell sequencing, which places us perfectly at the helm of this particular project - complex though it is considering the myriad branches represented by the protists we’re bound to find.

Look out for news soon of how you can get involved with our Darwin Tree of Life project, for which we’ll be harnessing the citizen scientists of Norfolk, UK to explore the “biodiversity on the [Norfolk] broads”.

 

Not only are they likely to have complex genomes, the protists are also going to be a lot more challenging to obtain samples of than other organisms, so we will need to look in soil, lakes and ponds to find them, like this veiny yellow Physarum slime mold.
Biology Dark Matter unseen life protists physarum slime mold 770

We are part of the Darwin Tree of Life project that aims to sequence all of the protists in the UK. That is no mean feat, as protists aren’t as easy to sample as some of the more flashy, larger wildlife such as mammals, birds, insects or trees.