More than three billion years ago, in the primordial soup that was the cradle of life on Earth, RNA took on many of the roles that its sister molecule DNA fills today — or so some scientists have speculated. A paper published 31 May in PLoS ONE posits one way that such an ‘RNA world’ could have worked: by making use of iron, a common element in the watery environs of ancient Earth.
In an RNA-dominated world, “RNA would have been the genetic material, and would have been the primary enzyme in metabolism,” says Loren Dean Williams, a chemist at the Georgia Institute of Technology in Atlanta and a co-author on the paper.
Today, RNA is best known as the messenger of genetic information, but large RNA molecules can fold into more complex structures, called ribozymes, with the ability to cut or glue other RNAs together. Magnesium ions (Mg2+) frequently stabilize charged phosphate ions in these globular RNA structures and allow it to fold and function as an enzyme — although not a very good one.
Williams, who studies ribosomes and ribozymes, became interested in how RNA might have operated in the very different chemical environment present in Earth’s early oceans. With oxygen almost entirely absent at that time, he notes, iron (Fe2+) and other metals could have been far more abundant in seawater than they are today. That all changed about 2.7 billion years ago, when primitive cyanobacteria started producing oxygen through photosynthesis, and iron gradually precipitated out of the ocean to form layer upon layer of a rusty, metallic rock known as ‘banded iron’ (pictured).
“We’re used to our world of oxygen, and oxygen and iron is just a terrible combination. They make a hydroxyl radical, and everything it hits loses a hydrogen, shredding RNA and proteins too,” says Williams.
Without oxygen in the mix, iron would no longer be a shredder of RNA and could instead serve as a potential co-factor in RNA folding, just as magnesium does. The Georgia Tech group calculated that the two metals produce a strikingly similar chemical geometry when binding to RNA. They also conducted laboratory tests comparing how iron and magnesium interact with RNA in the presence of various reagents to show that one could replace the other in a complex molecular structure.
Williams’s team then measured the enzymatic capability of two ribozymes in the absence of oxygen: L1 ligase, which glues RNA together, and the hammerhead ribozyme, which cuts up or cleaves RNA. With iron compared to magnesium, ligase saw a 25-fold higher initial activity rate, and the hammerhead saw a threefold higher initial activity rate.
“It actually makes perfect sense,” says Williams, who adds that because of iron’s atomic properties it is particularly adept at drawing electrons off RNA’s phosphate groups, potentially making them more susceptible to reaction.
“The exciting thing that they found is not only does it work — but it works a lot better,” says Robert Hazen, a research scientist at the Carnegie Institution for Science in Washington DC. Although their specific amounts are a mystery, “the ratio of iron to magnesium was much greater than it is today, so it makes sense that life would evolve to select the element that’s available and that works best,” says Hazen.
The gradual oxygen onslaught could have caused a shift in RNA folding and catalysis from iron to magnesium as iron became more toxic and less soluble. Other researchers have suggested that a similar shift occurred around the same time from iron to manganese in protein enzymes.
This suggested scenario is one of most interesting aspects of the new paper, says Steven Benner, an expert in the chemical origins of life and director of the Westheimer Institute at the Foundation for Applied Molecular Evolution in Gainesville, Florida. “It implies that the biology-driven creation of an [oxygen] atmosphere required the RNA catalysis at the core of biology to be replaced by proteins. These are big changes,” says Benner.
The Georgia Tech team will next explore RNA’s potential catalytic capabilities with iron, a list that includes electron transfer and redox chemistry. “As soon as you have iron and RNA together, it really expands the kind of chemistry that you can do,” says Williams. “RNA with iron is RNA on steroids.”