In search of the earliest life

Some 4 billion years ago, the first events leading to the formation of life occurred. What exactly they were will never be known.  

At the University of Minnesota, a team led by Burckhard Seelig wants to get as close to this event as they can. And not just for life’s earthly origin.

“We are interested in understanding how life could have started anywhere,” says Seelig, a professor in the College of Biological Sciences.

In their lab, the Seelig group uses amino acids—the building blocks of biology—and creates synthetic peptides and proteins to investigate the evolution of early life. Peptides are essentially mini proteins, composed of only a few amino acids, and were the likely ancestors of modern proteins.

His group also leads a NASA project to probe the origins of the genetic code, by which genes direct the production of proteins. NASA is interested in the origin of life on Earth and the potential presence of life beyond Earth.

For example, some amino acids have been recovered from the Murchison meteorite, which landed in Australia in 1969, and chemicals linked to earthly biochemistry have also been detected in the Gale Crater on Mars.

By creating new proteins, the Seelig team is also generating new tools for potential use in synthetic biology and biomedical applications.

Recreating the primordial soup 

To study the possible origins of life, the Seelig group simulates conditions that likely existed on Earth about 4 billion years ago, when life took its first steps. Perhaps it was the creation of peptides.  

The very first amino acids that joined together to form these ancestral peptides must have been made abiotically—that is, independently of life. 

“It appears that about half of modern amino acids likely have predated life,” Seelig says. “For example, they’ve turned up on meteorites, or they were made by purely chemical processes, so-called abiotic chemistry.” 

He and his colleagues give special attention to five amino acids that are thought to be among the most ancient, including the two with the simplest structures. At some point, some of these amino acids must have combined randomly to form the first ancestral peptides.  

“We want to find how random nonliving peptides could have led to the first biological proteins,” Seelig explains.

Evolution in a test tube?

To recreate a world with only primordial-like peptides, Seelig’s team must produce all kinds of peptides much faster than nature did 4 billion years ago. To do so, they synthesize a raft of random DNA sequences and translate them in a test tube into all kinds of peptides—10 trillion in all. They then test those peptides’ ability to behave similarly to modern proteins and peptides.

One test is whether the peptides bind to ATP, a simple molecule believed to have existed since the earliest days of life. Today it is a ubiquitous energy “currency” that stores energy from food, then releases it during interactions with enzymes or other proteins to fuel activities like cell growth or muscle contraction. At least some ancestral peptides would be expected to interact with ATP. 

The Seelig team also tests the peptides’ ability to interact with metal ions such as iron, copper, and zinc, which facilitate many of our bodies’ chemical reactions involving enzymes and ATP.

With tests of so many peptides, Seelig hopes to identify those whose formation could have been the first step in the evolution of life. He likens the tests to the mind game of giving enough monkeys enough typewriters (and paper):

“With 100 monkeys and 100 typewriters, at some point a monkey will write, ‘To be or not to be,’” Seelig says. “We make random peptides, 10 trillion of them, and play the monkey game.”