The Mystery of Homochirality on Earth

Abstract

Homochirality is an obvious feature of life on Earth. On the other hand, extraterrestrial samples contain largely racemic compounds. The same is true for any common organic synthesis. Therefore, it has been a perplexing puzzle for decades how these racemates could have formed enantiomerically enriched fractions as a basis for the origin of homochiral life forms. Numerous hypotheses have been put forward as to how preferentially homochiral molecules could have formed and accumulated on Earth. In this article, it is shown that homochirality of the abiotic organic pool at the time of formation of the first self-replicating molecules is not necessary and not even probable. It is proposed to abandon the notion of a molecular ensemble and to focus on the level of individual molecules. Although the formation of the first self-replicating, most likely homochiral molecule, is a seemingly improbable event, on a closer look, it is almost inevitable that some homochiral molecules have formed simply on a statistical basis. In this case, the non-selective leap to homochirality would be one of the first steps in chemical evolution directly out of a racemic "ocean". Moreover, most studies focus on the chirality of the primordial monomers with respect to an asymmetric carbon atom. However, any polymer with a minimal size that allows folding to a secondary structure would spontaneously lead to asymmetric higher structures (conformations). Most of the functions of these polymers would be influenced by this inherently asymmetric folding. Furthermore, a concept of physical compartmentalization based on rock nanopores in analogy to nanocavities of digital immunoassays is introduced to suggest that complex cell walls or membranes were also not required for the first steps of chemical evolution. To summarize, simple and universal mechanisms may have led to homochiral self-replicating systems in the context of chemical evolution. A homochiral monomer pool is deemed unnecessary and probably never existed on primordial Earth.

Keywords: chemical evolution; chirality; compartmentalization; conformation; digital immunoassay; enantiomeric excess; folding chirality; life on earth; nanopore; porous rock; prebiotic chemistry; protein folding; racemate; segregation; self-assembly; self-replication; single molecule level.

Figure 1

The discussion of homochirality is nearly always focused on asymmetric carbon atoms of monomeric subunits, such as the two enantiomers of the amino acid alanine here. Source: Synpath, Wikimedia, CC-BY-SA-4.0.

Figure 2

Secondary structures of small peptides with their (non-natural) mirror image. (a) A mutant ubiquitin peptide loop (PDB 1E0Q), consisting of 17 amino acids; (b) an antimicrobial peptide from Helicobacter pylori (PDB 1OT0), consisting of 20 amino acids. The well-formed secondary structures are obviously asymmetric and therefore chiral. Data and visualization are from the RCSB Protein Data Bank (PDB).

Figure 3

Tertiary structure of a protein with its (virtual) mirror image. (PDB 1KDF): North-Atlantic ocean pout antifreeze protein. Complex structures are essentially always asymmetric. Data and visualization are from the RCSB Protein Data Bank (PDB).

Figure 4

Random polymerization of a racemate always creates a small fraction of a peptide entirely consisting of homochiral monomers (marked by ✓). Regular letters mean one enantiomer, bold ones the other. 1/16 of the product molecules would be homochiral of a selected enantiomeric species. If we assume that the mirror molecule shows chemically the same properties, 1/8 of the oligomers would be homochiral, of one enantiomer or of the other. Created with BioRender.com.

Figure 5

Analogy of digital immunoassay and porous rock. A close-up of a volcanic pumice stone and a schematical result of a digital immunoassay are shown. The enzymatic product (green, fluorescent dye) is kept in a concentrated state by compartmentalization. Without the wells, the dye would be highly diluted and rendered undetectable. Left figure: Created with BioRender.com. Photo source: deltalimatrieste, Wikimedia: “Pomice di veglia.jpg”.