The simple protein that started all life

Scientists believe they have discovered a simple protein that started all life 3.5 to 2.5 billion years ago, publishing their findings 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,” says senior author Paul Falkowski from Rutgers University, US.

Proteins are complex three-dimensional shapes, created by infinite combinations of 20 amino acids, that power cells and organisms.

The astrobiology team, called ENIGMA (Evolution of Nanomachines in Geospheres and Microbial Ancestors), reasoned that, while today’s proteins are very complex, their predecessors had to be much simpler, explains co-author Vikas Nanda.

By identifying the first proteins, the team’s mission, sponsored by NASA, is to understand the origin and evolution of metabolism on Earth and potentially other planets.

“We hypothesise the first proteins were small, simple peptides (proteins with very short chains) that extracted energy from the environment in the form of electron-donating molecules in the ocean/atmosphere/rocks and moved them to other molecules that accept electrons,” says Nanda.

“Energy is released in this electron transfer reaction and this is the energy that drives all life.”

The scientists retraced the evolution of enzymes – proteins that catalyse chemical reactions – from the present to the distant past using computers and public databases of three-dimensional protein structures.

This built on current work in protein evolution which focuses on the sequence of amino acids encoded in DNA.

Using that paradigm, the evolutionary time that separates two proteins can be estimated by counting the number of mutations – the classic “molecular clock” model proposed by Zuckerkandl and Pauling in 1965.

“Mutations to DNA change this sequence,” Nanda explains, “and over time these mutations accumulate.”

But the number of changes blow out over long time scales spanning billions of years, making it impossible to recognise the proteins based on their sequence alone, Nanda explains.

Comparing the three-dimensional shapes of the proteins instead, which change much more slowly, his group revealed a small number of simple shapes used consistently by modern proteins.

And by focussing on metabolism, they could connect the protein shapes together into a network, a “wiring diagram” that shows how later proteins evolved to take electrons from earlier ones, thereby increasing life’s ability to extract energy from the planet.

“Using these two approaches – shape comparison and studying the wiring diagram of metabolism – we are inferring that two protein shapes were at the very root of metabolism,” Nando explains.

“Moreover, these two simple shapes share some features that lead us to propose an even simpler protein that could have been the root of metabolism.”

Now the group is making this and other potential early proteins in the lab to test “their ability to carry out chemical reactions that would have given the first living organisms an edge on the early Earth”.