- Part one: How to make a cell -
- Part two: A split in the ranks of scientists -
- Part four: the energy of protons -
- Part five: so how do you create a cell? -
- Part Six: The Great Unification -
So, after the 1960s, scientists trying to understand the origin of life fell into three groups. Some of them were convinced that life began with the formation of primitive versions of biological cells. Others believed the metabolic system was the key first step, while others focused on the importance of genetics and replication. This last group began to figure out what the first replicator might look like, assuming it was made from RNA.
Already in the 1960s, scientists had reason to believe that RNA was the source of all life.
In particular, RNA can do something that DNA cannot. It is a single-stranded molecule, so unlike rigid, double-stranded DNA, it can fold itself into a number of different shapes.
Similar to origami, the folding RNA was generally similar in behavior to proteins. Proteins are also mostly long chains - only of amino acids, not nucleotides - and this allows them to create complex structures.
This is the key to the most amazing ability of proteins. Some of them can speed up, or “catalyze,” chemical reactions. Such proteins are known as enzymes.
Many enzymes can be found in your intestines, where they break down complex molecules from food into simple types of sugars that your cells can use. It would be impossible to live without enzymes.
Leslie Orgel and Frances Crick were beginning to suspect something. If RNA can fold like a protein, maybe it can form enzymes? If this were true, then RNA could be an original - and universal - living molecule, storing information, as DNA does now, and catalyzing reactions, as some proteins do.
It was a great idea, but in ten years it hasn't gotten any proof.
Promotional video:
Thomas Cech, 2007
Thomas Cech was born and raised in Iowa. As a child, he was fascinated by rocks and minerals. And already in junior high school, he looked at the local university and knocked on the doors of geologists with a request to show models of mineral structures.
However, he eventually became a biochemist and focused on RNA.
In the early 1980s, Cech and colleagues at the University of Colorado at Boulder studied the single-celled organism Tetrahymena thermophila. Part of its cellular machinery includes RNA strands. Cech discovered that a single segment of RNA was somehow separated from the rest, as if it had been cut out with scissors.
When the scientists removed all enzymes and other molecules that could act as molecular scissors, RNA continued to be secreted. So they found the first RNA enzyme: a short piece of RNA that can cut itself out of the long strand of which it is a part.
Cech published the results of his work in 1982. The following year, another group of scientists discovered a second RNA enzyme, "ribozyme" (short for "ribonucleic acid" and "enzyme", aka enzyme). The discovery of two RNA enzymes one after the other indicated that there must be many more. And so the idea of starting life with RNA began to look solid.
However, the name of this idea was given by Walter Gilbert of Harvard University in Cambridge, Massachusetts. As a physicist with a fascination with molecular biology, Gilbert also became one of the early proponents of sequencing the human genome.
In 1986, Gilbert wrote in Nature that life began in the "RNA world."
The first stage of evolution, Gilbert argued, consisted of "RNA molecules performing the catalytic activity necessary to assemble themselves into a broth of nucleotides." By copying and pasting different bits of RNA together, RNA molecules could create even more useful sequences. Finally, they found a way to create proteins and protein enzymes that proved so useful that they largely supplanted the RNA versions and gave rise to the life we have.
RNA World is an elegant way to rebuild complex life from scratch. Rather than relying on the simultaneous formation of dozens of biological molecules from a primordial soup, a “one for all” molecule could do the job.
In 2000, the RNA world hypothesis received a colossal chunk of supporting evidence.
The ribosome makes proteins
Thomas Steitz spent 30 years studying the structure of molecules in living cells. In the 1990s, he devoted himself to his most serious task: figuring out the structure of the ribosome.
There is a ribosome in every living cell. This huge molecule reads instructions in RNA and arranges amino acids to make proteins. The ribosomes in your cells have built most of your body.
The ribosome was known to contain RNA. But in 2000, Steitz's team produced a detailed image of the ribosome structure, which showed that RNA was the catalytic core of the ribosome.
This was important because the ribosome is fundamentally important to life and very ancient at the same time. The fact that this essential machine was built on RNA made the RNA world hypothesis even more plausible.
Supporters of the "RNA world" triumphed, and in 2009 Steitz received a share of the Nobel Prize. But since then, scientists have begun to doubt. From the beginning, the idea of an RNA world had two problems. Could RNA really perform all the functions of life on its own? Could it have formed on the early Earth?
It has been 30 years since Gilbert laid the foundation for the "RNA world," and we still have not found solid evidence that RNA can do everything that theory requires of it. It is a small skillful molecule, but it may not be able to do everything.
One thing was clear. If life began with an RNA molecule, RNA had to be able to make copies of itself: it had to be self-replicating, self-replicating.
But none of the known RNAs can replicate itself. So is DNA. They need a battalion of enzymes and other molecules to create a copy or piece of RNA or DNA.
Therefore, in the late 1980s, several scientists began a very quixotic quest. They decided to create a self-replicating RNA on their own.
Jack Shostak
Jack Shostak of Harvard School of Medicine was one of the first to take part. As a child, he was so fascinated by chemistry that he started a laboratory in the basement of his house. Neglecting his own safety, he once even set off an explosion, after which a glass tube was stuck in the ceiling.
In the early 1980s, Shostak helped show how genes protect themselves from the aging process. This rather early study eventually earned him a piece of the Nobel Prize. However, very soon he admired Cech's RNA enzymes. “I thought this job was awesome,” he says. "In principle, it is entirely possible that RNA catalyzes its own reproduction."
In 1988, Cech discovered an RNA enzyme that can build a short RNA molecule 10 nucleotides long. Shostak decided to improve on the discovery by producing new RNA enzymes in the laboratory. His team created a set of random sequences and tested to see if any of them had catalytic abilities. Then they took those sequences, reworked them, and tested them again.
After 10 rounds of such actions, Shostak produced an RNA enzyme that accelerated the reaction by seven million times. He showed that RNA enzymes can be really powerful. But their enzyme couldn't copy itself, not even slightly. Shostak was at a dead end.
Maybe life didn't start with RNA
The next big step was taken in 2001 by former Shostak student David Bartel of the Massachusetts Institute of Technology in Cambridge. Bartel made the R18 RNA enzyme that could add new nucleotides to the RNA strand based on an existing template. In other words, he was not adding random nucleotides: he was copying the sequence correctly.
While it was not yet a self-replicator, but already something similar. R18 consisted of a chain of 189 nucleotides and could reliably add 11 nucleotides to the chain: 6% of its own length. It was hoped that a few tweaks would allow him to build an 189 nucleotide chain - just like himself.
The best thing was done by Philip Holliger in 2011 from the Molecular Biology Laboratory in Cambridge. His team created a modified R18 called tC19Z that copied sequences up to 95 nucleotides in length. That's 48% of its own length: more than the R18, but far from 100%.
An alternative approach was proposed by Gerald Joyce and Tracy Lincoln of the Scripps Institute in La Jolla, California. In 2009, they created an RNA enzyme that replicates indirectly. Their enzyme combines two short pieces of RNA to create a second enzyme. It then combines the other two pieces of RNA to recreate the original enzyme.
Given the availability of raw materials, this simple cycle can be continued indefinitely. But enzymes only worked when they were given the correct RNA strands, which Joyce and Lincoln had to do.
For many scientists who are skeptical of the "RNA world," the lack of self-replicating RNA is a fatal problem with this hypothesis. RNA, apparently, simply cannot take and start life.
The problem was also compounded by the failure of chemists to create RNA from scratch. It would seem a simple molecule compared to DNA, but it is extremely difficult to make it.
The problem lies in the sugar and base that make up each nucleotide. You can do each of them separately, but they stubbornly refuse to get involved. By the early 1990s, this problem had become apparent. Many biologists have suspected that the "RNA world" hypothesis, despite all its attractiveness, may not be entirely correct.
Instead, there may have been some other type of molecule on the early Earth: something simpler than RNA, which could actually pick itself up from the primordial soup and begin to replicate itself. First there could be this molecule, which then led to RNA, DNA and so on.
DNA could hardly have formed on the early Earth
In 1991, Peter Nielsen of the University of Copenhagen in Denmark came up with a candidate for primary replicators.
It was essentially a heavily modified version of DNA. Nielsen kept the same bases - A, T, C, and G - found in DNA - but made the backbone from molecules called polyamides, rather than from sugars, which are also found in DNA. He named the new molecule polyamide nucleic acid, or PNA. In an incomprehensible way, it has since become known as a peptide nucleic acid.
PNA has never been found in nature. But it behaves almost like DNA. The PNA strand can even take the place of one of the strands of the DNA molecule, and the bases are paired as usual. Moreover, PNA can twist into a double helix, like DNA.
Stanley Miller was intrigued. Deeply skeptical of the RNA world, he suspected that PNA was a much more likely candidate for the first genetic material.
In 2000, he produced some solid evidence. By then, he was already turning 70 and had suffered several strokes that could send him to a nursing home, but he did not give up. He repeated his classic experiment, which we discussed in the first chapter, this time using methane, nitrogen, ammonia and water - and got a polyamide base PNA.
This suggested that PNA, unlike RNA, could well have formed on the early Earth.
Threose nucleic acid molecule
Other chemists have come up with their own alternative nucleic acids.
In 2000, Albert Eschenmoser made threose nucleic acid (TNK). It's the same DNA, but with a different sugar at the base. TNC chains can form a double helix, and information is copied in both directions between RNA and TNK.
Moreover, TNCs can fold into complex shapes and even bind to proteins. This hints that TNK can act as an enzyme, like RNA.
In 2005, Eric Megges made a glycolic nucleic acid that can form helical structures.
Each of these alternative nucleic acids has its own proponents. But no traces of them can be found in nature, so if the first life really used them, at some point it had to completely abandon them in favor of RNA and DNA. This may be true, but there is no evidence.
As a result, by the mid-2000s, supporters of the RNA world found themselves in a quandary.
On the one hand, RNA enzymes existed and included one of the most important parts of biological engineering, the ribosome. Good.
But self-replicating RNA was not found and no one could understand how RNA was formed in the primordial soup. Alternative nucleic acids could solve the latter problem, but there is no evidence that they existed in nature. Not very good.
The obvious conclusion was that the "RNA world", despite its attractiveness, turned out to be a myth.
Meanwhile, a different theory gradually gained momentum since the 1980s. Its supporters argue that life did not begin with RNA, DNA, or other genetic material. Instead, it began with a mechanism for harnessing energy.
Life needs energy to stay alive
ILYA KHEL
- Part one: How to make a cell -
- Part two: A split in the ranks of scientists -
- Part four: the energy of protons -
- Part five: so how do you create a cell? -
- Part Six: The Great Unification -