All creatures great and
very, very small
UQ researchers are changing how we view some of the smallest aspects of the world, from the relationships between different bacteria to the very foundations of animal life.
If you’ve ever wondered where you come from and what combination of genes makes you who you are, the rise of at-home DNA test kits like 23andMe and AncestryDNA is fascinating.
These simple kits make it easy to satisfy your curiosity, in some cases even leading to the discovery of long-lost family or unexpected ancestry that has the potential to completely change the core of your identity.
Now, a different form of genetic testing has led to a discovery that could completely rewrite the ancestry of all animal life.
In research published in Nature on 12 June 2019, UQ researchers revealed their discovery that the first multicellular animals did not originate from a sponge-like type of creature called a choanocyte – as has been believed for over a century – but instead evolved from a collection of ‘convertible’ cells.
While this is literally a microscopic discovery, it is such a fundamental shift in our understanding of the origins of animal life that the macro-level impact could be staggering – ranging from biology textbooks being completely rewritten to potentially influencing the direction and timeline of future cancer and stem cell research.
“The great-great-great-grandmother of all cells in the animal kingdom, so to speak, was probably quite similar to a stem cell.”
Life on earth started with single-celled organisms that emerged, scientists think, approximately 3.5–4 billion years ago. Multicellular life first emerged around 2–3 billion years ago with microbes and algae, but the first hints of animal life didn’t appear until around 700 million years ago.
For a long time, scientists thought the earliest examples of animal life were these sponge-like choanocytes. This is because choanocyte cells in sponges today look very similar to choanoflagellates, single-celled microbes found in water that are considered to be the closest living relatives of animals.
“Most biologists for decades have believed this theory to be true, as sponge choanocytes look so much like single-celled choanoflagellates,” Associate Professor Sandie Degnan says.
“It’s one of those things that have always been in the textbooks, and people have always assumed, but no one has ever really tested,” says Assistant Professor Kevin M Kocot from the University of Alabama, who is a former National Institutes of Health postdoc in the Degnan Labs, and contributed to genetic data analysis for the project.
“Our findings show that it’s important to test the traditional hypothesis.”
Right: Desmarella moniliformis, a type of freshwater choanoflagellate. Credit: Sergey Karpov
The team used a new approach – single-cell transcriptomics or scRNA-Seq – to challenge this existing hypothesis.
Professor and Associate Professor Degnan were first drawn to this method because they were fascinated by the earliest step in animal evolution.
“By understanding these early steps, we uncover the most fundamental rules that govern the biology of all animals, including ourselves,” Professor Degnan says.
“We focused on an important part of the animal origins story – trying to uncover the ancestral cell type from which the entire animal kingdom evolved.
“Even though all animals are multicellular, we know they must have ultimately evolved from a single-celled ancestor.”
To do this, the team employed scRNA-Seq to look at what, and by how much, genes were expressed in single cells in the sponge, Amphimedon queenslandica.
They developed a way to quickly dissociate the sponge to single cells, and identify and isolated them for scRNA-Seq, focusing on cell types (choanocytes, pluripotent archaeocytes and pinacocytes) that scientists hypothesised were present at or before the dawn of the animal kingdom.
By examining the cells’ gene expression, which is the process by which information in the DNA is converted into a functional product such as a protein, the team were able to get an extremely detailed picture of these cell types, and their differences.
It was this information that showed them that the choanocytes and choanoflagellates were not actually similar to each other as expected. Instead pluripotent archeocytes, which have striking similarities to our own stem cells, were much more similar to choanoflagellates and other unicellular relatives. This suggests that the earliest multicelled animal ancestors were like modern stem cells, being able to transition between different states.
Another recent UQ study, using a different set of genomic approaches, has looked even deeper into our evolutionary past and has rewritten the taxonomy of bacteria, again showing us that we don’t know nearly as much about it as you might think.
Taxonomy is the science that classifies living things and helps scientists understand how organisms are related to each other – essentially, it’s the family tree of all life on earth.
The study published in Nature Biotechnology and led by UQ’s Professor Philip Hugenholtz used another type of genetic sequencing to overhaul the evolutionary tree of bacterial classification.
Professor Hugenholtz, who is the Director at UQ’s Australian Centre for Ecogenomics (ACE), says the scientific community generally agrees that evolutionary relationships are the most natural way to classify organisms, but this has traditionally posed a lot of difficulties in the bacterial world.
“Microbial species have very few distinctive physical features, meaning that there are thousands of historically misclassified species,” he says.
"The existing system has a lot of errors in it, partly due to historical baggage of classifying microorganisms based on how they look and what they do, which doesn’t necessarily match how they are related to each other.”
“We now know that classifying organisms according to their evolutionary relationships is widely regarded as the best approach to biological classification.
“The genome is the best evolutionary document we have available to us, so we are sequencing microbial genomes at an unprecedented rate, providing the raw material for a very accurate, very detailed classification system.
“Using this genomic material, we have created the genome taxonomy database (GTDB).”
Image: This diagram demonstrates how the researchers normalised ranks in the GTDB classification, contouring the taxonomy to an evolutionary tree. This demonstrates that ancestral organisms belonging to the same taxonomic rank co-existed in the past, allowing scientists to infer important biological processes such as lateral gene transfer, which occurs between co-existing organisms.
The GTDB – an initiative to establish a standardised microbial taxonomy based on genome phylogeny – has been very positively received by the scientific community since its launch in 2018.
“Most researchers are attracted to the systematic aspects of the proposed microbial taxonomy, which fixes the current issues and follows as closely as possible the evolutionary history of microorganisms – specifically removal of polyphyletic taxa, taxa lacking a common ancestor, and normalisation of taxonomic ranks,” Professor Hugenholtz says.
By using a technique called metagenomics, which studies genetic material taken directly from environmental samples, his team were able to create a more completed picture of the structure of microbiology.
“We can now get the entire genetic blueprints of hundreds of thousands of bacteria, including bacteria that have not yet been grown in the lab,” says Dr Donovan Parks from ACE, who was the lead software developer on the project.
Now, animals may be taking a new place on the tree of life, branching out from convertible cells instead of the previously assumed branch of choanocytes.
So, what does this all mean?
“We’re taking a core theory of evolutionary biology and turning it on its head,” Associate Professor Degnan says.
“One of the reasons we study these kinds of questions, is we try and strip back all of the complexity and see the fundamental rules that govern the processes that are critical for our own health – such as cancer and stem cells.
“The actual underlying rules that affect humans in such dramatic ways were forged almost a billion years ago, but they’re not unique to humans at all.
“However, understanding them does have an enormous impact on our ability to improve humanity’s overall knowledge base.
“We hope this correction of our understanding about the origins of animal life will lead to future applications – like medical breakthroughs – that improve health and wellbeing for all animal life.”
The story so far
2010: UQ's Bernie and Sandie Degnan, with collaborators in the USA, Germany, Canada and France, publish the genome of a coral reef sponge in Nature, dispelling long held views on animal complexity and evolution. This landmark genome project is the first published from the Great Barrier Reef.
2010: The Degnans work with Sir David Attenborough on the Emmy Award winning series First Life, where Sir David highlights the importance of sponges in animal evolution and the Degnans show how sponges can be dissociated down to single cells.
2010: The Australian Centre for Ecogenomics, led by Professor Philip Hugenholtz, is established at UQ.
2012–2016: PhD students, postdoctoral scientists and technicians in the Degnan Labs at UQ develop techniques to identify and manually isolate single cells, and with collaborators in Israel develop a scRNA-Seq technique called CEL-Seq to profile the transcriptomes (the RNA) of single cells and embryos.
2016: The Degnan Labs contribute to a key paper published in Nature with Israeli colleagues and other research teams from the USA, Germany and Israel using CEL-Seq to understand the origin and evolution of animal development.
2016: Professor Hugenholtz is awarded a prestigious ARC Laureate Fellowship for his research in microbial ecology and genomics.
2017: Professor Hugenholtz is inducted as a Fellow of the Australian Academy of Sciences in Canberra for his landmark contributions to the understanding of uncultured microbial diversity, evolution and ecology.
2018: The genome taxonomy database (GTDB) is launched, and the results of the study are published in Nature Biotechnology.
June 2019: Publication of “Pluripotency and the origin of animal multicellularity” in Nature from research undertaken in the Degnan Labs between 2012 and 2017 by former PhD students Shunsuke Sogabe, William Hatleberg, Tahsha Say and Daniel Stoupin, who now hold positions in the USA, UK and Australia, and former postdoctoral scientists Kevin Kocot, Kerry Roper and Selene Fernandez-Valverde, who now hold positions in the USA, Australia and Mexico.
Professor Philip Hugenholtz, School of Chemistry and Molecular Biosciences
Article last updated on 12 June 2019.