Polyelectrolyte theory of the gene

The polyelectrolyte theory of the gene proposes that for a linear genetic

Benner and others who built on his work[5] have proposed methods for how to concentrate and identify genetic biopolymers on other planets and moons within the solar system using electrophoresis, which uses an electric field to concentrate charged compounds.^[1][2][3]

Although few have tested the polyelectrolyte theory of the gene, in 2019, lab experiments challenged the universality of this idea. This work was able to create non-electrolyte polymers capable of limited Darwinian evolution, but only up to a length of 72 nucleotides.^[6][7]

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The polyelectrolyte theory of the gene attempts to understand modern biology’s unit of inheritance, DNA, at a generalizable level. In 2002, Steven A. Benner and Daniel Hutter identified the repeated charges in DNA's phosphodiester linkages as crucial to its function as a genetic biopolymer. They proposed with the polyelectrolyte theory of the gene that repeated ionic charges—positive or negative—are a general requirement for all water-dissolved genetic biopolymers to undergo Darwinian evolution anywhere in the cosmos.[2]

This concept works in tandem with the view of the gene as an "aperiodic crystal" as proposed by Erwin Schrödinger in his 1944 book "

In biochemistry, the structure of a biomolecule dictates its function, and therefore changes in structure cause changes in function.^[14] To work as a unit of inheritance, the genetic biopolymer must maintain shape and, therefore, physical and chemical consistency, regardless of the information the structure encodes. DNA is such a molecule. No matter what the nucleic acid sequence is, DNA maintains a consistent double helix structure and, therefore, the consistent physical properties that allow it to remain dissolved in water and be replicated by cellular machinery. The polyelectrolyte theory of the gene reasons that DNA can maintain its shape regardless of mutations because the negative charges on the phosphate backbone dominate the physical interactions of the molecule to such a degree that changes in the nucleic acid sequence, the encoded information, do not affect the overall physical behavior of the molecule.^[2]

For example, thymidine nucleotides (T) are very soluble in water while guanosine nucleotides (G) are more insoluble; however, an oligonucleotide—a short polynucleotide sequence—composed of only thymine and one composed of only guanine has the same overall structure and physical properties.^[15] If changes in the nucleic acid sequence, which encodes genetic information, change the physical properties of DNA, these changes could break down the mechanism by which DNA replicates.

This physical uniformity is very rare in nature. Take another biopolymer, for example, proteins. The nucleic acid sequence in DNA codes for the sequence of amino acids that make up proteins. A change to even a single amino acid in the primary sequence of a protein can completely change the physical properties of that protein. For example, the sickle-cell trait is caused by a single mutation of an adenine to a thymine in the hemoglobin gene, causing a switch from a glutamic acid to a valine.^[16] This completely changes the three-dimensional structure of hemoglobin and thus changes the physical properties of the protein that lead to the sickle-cell trait.

Proteins are sensitive to changes in amino acid sequence because the 20 different amino acid side chains form bonds and partial bonds with each other.

Benner and Hutter initially described this property of DNA as being "capable of surviving modifications in constitution without loss of properties essential for replication" or the acronym COSMIC-LOPER. This acronym gives scientists a shorthand way of describing the complex idea of a genetic biopolymer having the physical uniformity regardless of encoded information that allows it to be replicated.[2]

Although RNA is often described as a genetic biopolymer because of its theorized role as life’s first unit of inheritance (RNA World), it is not entirely COSMIC-LOPER. RNA, especially sequences high in guanine (G), is capable of folding and performing enzyme-type chemistry.^[2][18] Folding in guanine-rich RNA sequences prevents the templating ability of RNA and thus its ability to be replicated in an RNA-world scenario, for the same reason it would be difficult for a protein-based gene to replicate.^[2]

The repeated negative charges increase the solubility of DNA and RNA in water. Because ionic charges are highly soluble in water, having them on the molecule's backbone increases the molecule's solubility.^[19] If the backbone of a hypothetical genetic biopolymer were linked together in a non-ionic fashion, the solubility of the whole molecule would decrease.^[20] Solubility is important because, in order to be replicated, DNA—or any other genetic biomolecule—must be soluble to interact with replicative machinery.^[11]

The repeated negative charges of the DNA backbone

The closest non-electrolyte analog to maintaining the qualities of DNA was the polyamide-linked nucleic acid analog (PNA), which replaced the phosphodiester linkage of DNA with an uncharged N-(2-aminoethyl)glycine linkage. Even Benner and Hutter questioned if PNA might disprove their polyelectrolyte hypothesis; however, even though PNA maintained the qualities of DNA up to a length of 20 nucleotides, beyond that length, the molecules started to lose Watson–Crick base pair specificity, aggregated, and became sensitive to changes in nucleic acid sequence.^[2]

In 2019, a group led by

Since its inception, the polyelectrolyte theory of the gene has been put in the context of searching for life in the universe. This theory, combined with Schrödinger's view of a gene as an aperiodic crystal, provides a so-called "agnostic biosignature",^[1] a sign of life that does not presuppose any biochemistry.^[27] In other words, a generalized view of life should hold anywhere in the universe.^[1]

Since the theorized genetic polyelectrolyte biomolecules could be charged either positively or negatively, as in the case of DNA and RNA, they can be concentrated in water with an electric field using electrophoresis or electrodialysis. This hypothetical concentration device has been called an agnostic life-finding device.^[1] Similar to how electrophoresis works to separate DNA molecules, negatively charged molecules, like DNA or RNA, would be attracted to a positively charged anode, and positively charged genetic biomolecules would be attracted to a negatively charged cathode.^[15]

Once the polyelectrolyte biomolecule has been concentrated, Benner suggests the molecules be tested for size and shape uniformity. In addition, the molecules should be tested for the use of a limited number of building blocks arranged in a non-repeating fashion, an aperiodic crystal structure.^[1] Benner has suggested that this could be done using matrix-assisted laser desorption ionization (MALDI) paired with an orbitrap high-resolution mass spectrometer.^[28] Another suggested approach has been to use nanopore sequencing technology, although questions of whether the solar radiation experienced during transit and on-site would affect the functionality of the device remain.^[5] While space agencies have yet to use any of these proposed systems for life detection, they may be used in the future on Mars,^[28] Enceladus,^[1] and Europa.^[5]

Despite the polyelectrolyte theory of the gene and the aperiodic crystal view of the gene being described as agnostic biosignatures, these theories are terra-, or earth-life, centric. It is unknown what life on another world might be; while it is often stated that life of any kind needs biomolecules and water, this may not be true.^[19]