Protein space

Study: Structure of 3.5 billion-year-old molecules could help us find aliens

This may be the biological signature we need to find life on other planets.

IgG2a monoclonal antibody (immunoglobulin), 3D rendering. Many biotech drugs are antibodies. Cartoon...

A tiny, prehistoric Earth molecule could pave the way for finding life out in the cosmos.

That's the upshot of a new study detailing the oldest molecules ever found responsible for metabolism. The research not only hints at some of the most-ancient building blocks for all life on Earth; it also provides the foundation for chemical signals that could help us find life in space in the future.

In the paper, a team of researchers from Rutgers University’s team ENIGMA and NASA scientists detail the evolution of proteins as far back as 3.5 billion years ago.

The findings were published Monday in the journal Proceedings of the National Academy of Sciences.

"We think we have found the building blocks of life — the Lego set that led, ultimately, to the evolution of cells, animals and plants,” study senior author Paul G. Falkowski, ENIGMA principal investigator, said in a statement.

Protein power

Metabolic proteins are essentially chains of amino acids that convert nutrients into energy in any living organism.

““They're like little machines. We call these proteins nanoscale machines,” Vikas Nanda, professor at Rutgers University and co-author on this study, tells Inverse.

“These are the things that digest food, act as chemical signals in our body, hemoglobin transport, transport the oxygen through our body.”

To understand the origin of life on Earth, the researchers forensically reconstructed what proteins were like almost 4 billion years ago — a complicated feat given that there are no fossils — and thus, no organic molecules — from that time.

But as organisms evolve and adapt over the years, researchers can look to genetic sequencing to track how much proteins have changed over the course of 10 million years, Nanda says.

“But when you get to a billion years, sequences are no longer useful because there are so many changes that you can't even recognize,” Nanda says. So instead, the team looked at the shape, not the sequence, of the amino-acid chains for clues. These shapes and folds are more resilient to change than the sequences of proteins, which means they can reveal what proteins might have looked like when they first emerged on Earth.

“A protein starts off as a chain of amino acids, but then it folds into a three-dimensional structure, a shape that is what actually gives the protein its function,” Nanda says.

“They kind of look almost like ribbons that are sort of like wrapped around and tied together.”

This image shows a fold (shape) that may have been one of the earliest proteins in the evolution of metabolism.

Vikas Nanda/Rutgers University

Using data from the Protein Data Bank, a publicly available database for protein experimental data, Nanda and his team used computer modeling to look for patterns to determine common functions.

“If you see a bike and you see a car, and you see a train, all of them have wheels, and so we can see that the wheel is a conserved shape that is used again and has the same function in all those cases,” Nanda says. The same applies to proteins: Common features may reveal these ancestral proteins' features.

The researchers zeroed in on two of these folds: The ferredoxin fold, which binds iron-sulfur compounds and shifts electrons around so that metabolism can take place, and the Rossmann fold, which is involved in making DNA.

Both the folds appear to have ancient ancestry, the study suggests. And, if the findings hold true, they may be the root of metabolism — the essential process for life, and a potential signature for life on other worlds.

Extraterrestrial enzymes

Understanding how protein shapes evolved over the course of life on Earth could help propel the future of astrobiology.

"The findings in the paper are exciting. By proposing a simple structural template, this research helps ongoing and future efforts to design rudimentary enzymes," Hue Sun Chan, professor at the University of Toronto, tells Inverse. Sun Chan was not involved with the research.

Ultimately, this could help us in a search for life elsewhere, he says.

"This in principle could help us look for similar environments in other planets as a means to assess the likelihood of emergence of life in a given planet."

And that is the goal of the ENIGMA group. Nanda's team works with NASA to try and identify life on other planets and moons. But when it comes to finding alien life, it helps to have an idea of what you are looking for.

"When we send a lander to Europa or Titan or some other place in the solar system, they want to make sure they do the right experiments,” Nanda says.

“They want to model what the evolution of life may look like on other planets so that they can then have these instruments look for the signals that would correspond.”

“With the origins of life on our planet, then we could extrapolate that to other worlds."

An important caveat to this study is that it is only a predictive model. The next step is to try and build these ancient proteins in the lab and see if the findings bear out, Nanda says.

"We already have been testing many molecules for the past seven or eight years. And what this project has done now is it suggested even more molecules for us to look at," he says.

“Metabolism is not going to be just one protein. It's going to be just like it is in ourselves. We have thousands of proteins that are interacting together,” Nanda tells Inverse.

“If we start to see peptides or proteins in interstellar material from asteroids or when we land on other planets or moons in the solar system,” Nanda tells Inverse, mentioning that this has happened recently.

“If those peptides have some of the same chemical properties as the ones that we are making in the laboratory, then that would be a pretty strong indication that they have a biological function.”

Having a biological function would mean that they are a signature that there is some sort of a living process going on. This, “certainly helps us know what to look for,” Nanda says.

"An essential step forward is to artificially design rudimentary enzymes that are functional. Apparently several labs are doing it."

In fact, this study only stopped at the prediction. It doesn't test the prediction in any sort of tangible way, according to Nanda himself. The next steps will be to actually try these proteins out.

“But we already have been testing many molecules for the past seven or eight years. And what this project has done now is it suggested even more molecules for us to look at.”

Abstract: Life on Earth is driven by electron transfer reactions catalyzed by a suite of enzymes that comprise the superfamily of oxidoreductases (Enzyme Classification EC1). Most modern oxidoreductases are complex in their structure and chemistry and must have evolved from a small set of ancient folds. Ancient oxidoreductases from the Archean Eon between ca. 3.5 and 2.5 billion years ago have been long extinct, making it challenging to retrace evolution by sequence-based phylogeny or ancestral sequence reconstruction. However, three-dimensional topologies of proteins change more slowly than sequences. Using comparative structure and sequence profile-profile alignments, we quantify the similarity between proximal cofactor-binding folds and show that they are derived from a common ancestor. We discovered that two recurring folds were central to the origin of metabolism: ferredoxin and Rossmann-like folds. In turn, these two folds likely shared a common ancestor that, through duplication, recruitment, and diversification, evolved to facilitate electron transfer and catalysis at a very early stage in the origin of metabolism.
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