Artificial molecules

Origins research is beginning to really heat up (hilarious pun intended). One team of researchers is working with RNA (but then again, who isn’t?)

A new molecule that performs the essential function of life – self-replication – could shed light on the origin of all living things.

If that wasn’t enough, the laboratory-born ribonucleic acid (RNA) strand evolves in a test tube to double itself ever more swiftly.

“Obviously what we’re trying to do is make a biology,” says Gerald Joyce, a biochemist at the Scripps Research Institute in La Jolla, California. He hopes to imbue his team’s molecule with all the fundamental properties of life: self-replication, evolution, and function.

By building a molecule that can self-replicate, Joyce’s team has shown a pretty solid principle of how scientists believe life began: begin with something simple which makes copies of itself, then…

Not content with achieving one hallmark of life in the lab, Joyce and Lincoln sought to evolve their molecule by natural selection. They did this by mutating sequences of the RNA building blocks, so that 288 possible ribozymes could be built by mixing and matching different pairs of shorter RNAs.

What came out bore an eerie resemblance to Darwin’s theory of survival of the fittest: a few sequences proved winners, most losers. The victors emerged because they could replicate fastest while surrounded by competition, Joyce says.

As Joyce notes, this isn’t truly life. It’s a very promising experiment, however, and that’s where the excitement lay. By inducing mutations, evolution began to take place. It’s so simple a child can understand it.

Origins

It’s only a matter of time until something very much like life is created in the lab. Until then, scientists are still working on how it happened, nearly 4 billion years ago. The research is promising.

With the aid of a straightforward experiment, researchers have provided some clues to one of biology’s most complex questions: how ancient organic molecules came together to form the basis of life.

Specifically, this study demonstrated how ancient RNA joined together to reach a biologically relevant length.

RNA, the single-stranded precursor to DNA, normally expands one nucleic base at a time, growing sequentially like a linked chain. The problem is that in the primordial world RNA molecules didn’t have enzymes to catalyze this reaction, and while RNA growth can proceed naturally, the rate would be so slow the RNA could never get more than a few pieces long (for as nucleic bases attach to one end, they can also drop off the other).

Ernesto Di Mauro and colleagues examined if there was some mechanism to overcome this thermodynamic barrier, by incubating short RNA fragments in water of different temperatures and pH.

They found that under favorable conditions (acidic environment and temperature lower than 70 degrees Celsius), pieces ranging from 10-24 in length could naturally fuse into larger fragments, generally within 14 hours.

The RNA fragments came together as double-stranded structures then joined at the ends. The fragments did not have to be the same size, but the efficiency of the reactions was dependent on fragment size (larger is better, though efficiency drops again after reaching around 100) and the similarity of the fragment sequences.

The researchers note that this spontaneous fusing, or ligation, would [be] a simple way for RNA to overcome initial barriers to growth and reach a biologically important size; at around 100 bases long, RNA molecules can begin to fold into functional, 3D shapes.

Enzymes basically make things go faster. That means that reactions that are caused by a particular protein (say, lactase breaking down lactose into its constituents – if you can’t do this or do it poorly, you’re lactose intolerant) can happen anyway, but they will happen far more slowly. In some instances, they essentially will not happen except by tremendous stroke of luck (though, again, the potential is always there).

What’s particularly interesting to note here is that it is very difficult to say what the pH balance of different bodies of water would be on an early Earth. It is entirely plausible that acidic levels would be higher, leading to the ability of these RNA molecules to form 3D shapes. And, of course, because biology is very much dependent on shape, these formations could act as proteins, if not plainly be defined as such. By doing this, a rudimentary evolution could begin to take place. We may not define these replicators as being life, but they would hold many of its characteristics – taking in energy and out, being subject to at least a form of natural selection.

A theory in crisis!

A theory in crisis.

A team of Canadian and French scientists has shed new light on what’s being called the Earth’s “last universal common ancestor,” the 3.8-billion-year-old microscopic organism from which all living things – bacteria and humans and sunflowers alike – evolved.

The researchers, including Universite de Montreal evolutionary geneticist Nicolas Lartillot and colleagues from the Universite de Lyon, say they’ve discovered that “LUCA” was not the heat-craving entity scientists have traditionally believed it to be. Instead, the team argues in the journal Nature, the primitive speck of life that became mother and father to all plants and animals preferred relatively cool temperatures of less than 50 C – not the 90 C habitat generally assumed to be its ideal simmering temperature in life’s primordial soup.

“It is generally believed that LUCA was a heat-loving or ‘hyperthermophilic’ organism – a bit like one of those weird organisms living in the hot vents along the continental ridges deep in the oceans today,” said Nicolas Lartillot, a bio-informatics professor at the U de M. “However, our data suggests that LUCA was actually sensitive to warmer temperatures and lived in a climate below 50 degrees.”

The study states that the initial offspring lineages of the common ancestral life form must have adapted later to higher temperatures, “possibly in response to a climate change of the early Earth.”

The study provides a new look at the planet’s biological beginnings – even before the rudimentary chemical ingredients of life had assembled into DNA strands that would become fundamental to evolution.

“The group’s findings are an important step toward reconciling conflicting ideas about LUCA,” a research summary states. “In particular, they are much more compatible with the theory of an early RNA world, where early life on Earth was composed of ribonucleic acid (RNA), rather than deoxyribonucleic acid (DNA).”

The researchers note that heat-sensitive RNA was “unlikely to be stable in the hot temperatures of the early Earth” but that LUCA must have found “a cooler micro-climate” in which to develop.

“It is only in a subsequent step that LUCA’s descendants discovered the more thermostable DNA molecule, which they independently acquired (presumably from viruses), and used to replace the old and fragile RNA vehicle,” Lartillot said in the statement. “This invention allowed them to move away from the small, cool micro-climate, evolve and diversify into a variety of sophisticated organisms that could tolerate heat.”

Oh, hang on. It looks like scientists are just debating how evolution occurred, not whether it occurred. Business as usual.