Cite as: Benner, S. A. (2021) “Synthetic Biology Suggests a Universal Sign of Life in the Chemistry of Genetic Molecules”. Primordial Scoop, 2021, e0208. https://doi.org/10.52400/QQKR8269
Life, according to NASA, is a “self-sustaining chemical system capable of Darwinian evolution”. Some have criticized this “definition” as not being “operational”, that is, it cannot be put into practice in a mission to (for example) Mars to detect Martian life. Our rovers cannot take a sample of Martian water and wait a few decades to see if the specks within it evolve.
Thinking for a bit, however, that criticism is not particularly imaginative. Consider Mr. and Mrs. Rabbit, pictured below. We should be able to infer from observing the rabbit that it is capable of Darwinian evolution without needing to wait for them to evolve. Or, for that matter, without needing to wait even for them to produce Baby Rabbit.
Of course, for Mr. and Mrs. Rabbit, knowledge of mammalian reproductive biology helps us “cheat”. We know where to look for ovaries and testis. We also know that they are warm and mobile. But that approach does not likely help us on Mars, where the organisms are likely to be micro, not macro, and have a natural history different from life on Earth. Even multicellular Martians, we do not expect to share the peculiarities of mammalian reproductive physiology. As we learned in Star Trek VI: “Not every species has their genitals in the same place, Captain”.
No, to find universalities in Darwinian evolution, we must turn to molecules that support it. In Terrans, that molecule is DNA. DNA is an informational polymer with a backbone that contains repeating negatively charged phosphate groups, linked by sugar building blocks that carry nucleotide bases. There are four nucleotide bases (A (adenine), T (thymine), G (guanine), and C (cytosine)), and their sequence on the phosphate-sugar backbone encodes the information that tells a rabbit how to be … well … a rabbit.
DNA supports Darwinian evolution as an informational polymer. That is for sure. But if there is extraterrestrial life, would it use the same biopolymer? Will all forms of life use it, exactly as on Earth? And, in particular, will Martians use it?
For this, we turn to synthetic biology, the field where scientists have synthesized polymers whose structures are different from Terran DNA, but which can still support Darwinian evolution. As with many accomplishments in science, the path to developing these novel information-carrying molecules is littered with successes and failures. Both the success and failures lead us to the insight that, to be capable of Darwinian evolution, a molecule must have a few easily-identifiable properties.
First, let’s discuss a success story. As we analyzed previously on this blog, a novel informational polymer can be made by changing the nucleotide bases that make the genetic alphabet. We have made alternative forms of DNA that have as many as 12 different bases. We gave our synthetic bases one-letter names, like the Z:P pair, the S:B pair, the K:X pair, and the V:J pair. These can be added to the DNA backbone alongside the naturally-occurring A:T and G:C pairs. Many of the molecules that contain synthetic bases have been shown to be able to evolve.
But one conclusion was made clear by these efforts. To support Darwinian evolution, all of the replaceable pairs must have the same size and shape. That is, if the novel base pairs (e.g. Z:P and S:B) weren’t designed to be the same size as the natural A:T and G:C pairs, including them alongside the natural bases would distort the shape of the DNA molecule.
This concept of structural uniformity despite changing information was proposed by physicist Erwin Schrödinger (the same Schrödinger who had an “equation” and a “cat”) in 1943. Schrödinger noted that for faithful information replication, the informational units replaced during evolution all must fit what he called an “aperiodic crystal structure”.
To be “aperiodic”, a crystal must have two properties:
- It must have multiple constituent parts, which allow it to encode information (unlike, for example, ice crystals, which are pure water), and
- it must retain a highly ordered microscopic structure, regardless of how its constituents are arranged.
DNA is an example of an aperiodic crystal. You can re-order its constituents — the nucleotide bases– without changing the structure of the double helix. We have remarked on this blog that this concept by itself can be used to rule out certain models for the origin of molecular Darwinism on Earth.
So here is a rule: The bases in Terran DNA are not universal, but the size uniformity of their pairs is. Excellent.
What other rules did synthetic biology find? The backbone of DNA has alternating sugars and phosphates. The sugars are not universal. We, Piet Herdewijn, Albert Eschenmoser, and many others, synthesized perfectly acceptable informational biopolymers by replacing these.
However, the phosphates were different. We had difficulty replacing these phosphates, as did many other scientists. This failure was instructive, pointing towards another invariant in molecular information storage: not only must the molecular size and shape must be invariant upon changing information content, so must be bulk molecular behavior.
What do we mean by “bulk behavior? Many things, but here are a few. Informational molecules must dissolve in water; changing their information content must not cause the molecule to precipitate. Additionally, informational molecules must interact with other molecules to transfer information. Changing their information content must not destroy their interactions.
Why are phosphates in the backbone of DNA important for this? The answer requires some discussion of organic chemistry, molecular structure, and the distribution of electrons that hold that structure together. Briefly, in water, which is (for other reasons) where life is universally expected to be found, the most important feature of a molecule is its charge. Salt, which is sodium with a positive charge and chloride with a negative charge, dissolves in water.
And so does DNA. This is because the phosphates in the backbone of DNA each have a negative charge. As each informational unit has a charge, because a DNA gene can have thousands of these informational unit, each gene has thousands of negative charges. This makes them very soluble in water.
Further, these charges remain even as building blocks are exchanged. This means that no matter the information content of the gene, the DNA never precipitates.
For contrast, proteins show how a biopolymer behaves when repeating backbone charges are not present. Proteins are a string of amino acids, whose order also contains information. However, unlike DNA, the three-dimensional structure of a protein can change dramatically from even a slight modification in the order of its amino acids. For example, just one amino acid replacement in hemoglobin, the protein that carries oxygen in our blood, which is a chain of ~150 amino acids, causes it to precipitate, creating the molecular disease known as “sickle cell anemia”.
Of course, having a biopolymer that dramatically changes its phenotype upon small changes in its sequence can be useful, e.g. for the evolution of specialized functional capabilities. However, this property makes proteins very poor information carriers. Imagine the poor organism whose genetic molecule precipitates when an A:T pair is replaced by a G:C pair.
Now, a molecule like DNA with a repeating charge is called a polyelectrolyte. And so these observations, ideas, and experiments generated the “Polyelectrolyte Theory of the Gene.” That theory says that all genes in water, no matter what the planet, will have a repeating backbone charge; molecular manifestations of evolvable information will always be polyelectrolytes. The repeating backbone charge can be negative, like the phosphate links in DNA. Or it can be positive. Anyone seeking to detect life agnostically, without knowing already the exact molecules that Martian rabbits use to have babies, would look for both.
And so it is time now to look for Martian rabbits, or their microbial counterparts. It may soon be too late. Emerging technology and the democratization of space travel means that humans will soon be on Mars. Once they are there, Martian life will be more difficult to find. And perhaps impossible to find.
There is no need to fret. We must simply now build an instrument to find the polyelectrolytes in Martian water. Once they are found, all we must do is see if their building blocks fit Schrödinger’s rule. If they do, we will have found life on Mars.
And a new age of biology will begin.
