Prebiotic access to enantioenriched amino acids via peptide-mediated transamination reactions.

The kinetic resolution of racemic amino acids mediated by dipeptides and pyridoxal provides a prebiotically plausible route to enantioenriched proteinogenic amino acids. The enzymatic transamination cycles that are key to modern biochemical formation of enantiopure amino acids may have evolved from this half of the reversible reaction couple. Kinetic resolution of racemic precursors emerges as a general route to enantioenrichment under prebiotic conditions.

Oxazolone mediated peptide chain extension and homochirality in aqueous microdroplets.

Peptide formation from amino acids is thermodynamically unfavorable but a recent study provided evidence that the reaction occurs at the air/solution interfaces of aqueous microdroplets. Here, we show that i) the suggested amino acid complex in microdroplets undergoes dehydration to form oxazolone; ii) addition of water to oxazolone forms the dipeptide; and iii) reaction of oxazolone with other amino acids forms tripeptides. Furthermore, the chirality of the reacting amino acids is preserved in the oxazolone product, and strong chiral selectivity is observed when converting the oxazolone to tripeptide. This last fact ensures that optically impure amino acids will undergo chain extension to generate pure homochiral peptides. Peptide formation in bulk by wet-dry cycling shares a common pathway with the microdroplet reaction, both involving the oxazolone intermediate.

Extreme accumulation of ammonia on electroreduced mackinawite: An abiotic ammonia storage mechanism in early ocean hydrothermal systems.

An increasing amount of evidence suggests that early ocean hydrothermal systems were sustained sources of ammonia, an essential nitrogen species for prebiotic synthesis of life's building blocks. However, it remains a riddle how the abiotically generated ammonia was retained at the vent-ocean interface for the subsequent chemical evolution. Here, we demonstrate that, under simulated geoelectrochemical conditions in early ocean hydrothermal systems ([Formula: see text][Formula: see text] V versus the standard hydrogen electrode), mackinawite gradually reduces to zero-valent iron ([Formula: see text]), generating interlayer [Formula: see text] sites. This reductive conversion leads to an up to 55-fold increase in the solid/liquid partition coefficient for ammonia, enabling over 90% adsorption of 1 mM ammonia in 1 M NaCl at neutral pH. A coordinative binding of ammonia on the interlayer [Formula: see text] sites was computed to be the major mechanism of selective ammonia adsorption. Mackinawite is a ubiquitous sulfide precipitate in submarine hydrothermal systems. Given its reported catalytic function in amination, the extreme accumulation of ammonia on electroreduced mackinawite should have been a crucial initial step for prebiotic nitrogen assimilation, paving the way to the origin of life.

Sequence self-selection by cyclic phase separation.

The emergence of functional oligonucleotides on early Earth required a molecular selection mechanism to screen for specific sequences with prebiotic functions. Cyclic processes such as daily temperature oscillations were ubiquitous in this environment and could trigger oligonucleotide phase separation. Here, we propose sequence selection based on phase separation cycles realized through sedimentation in a system subjected to the feeding of oligonucleotides. Using theory and experiments with DNA, we show sequence-specific enrichment in the sedimented dense phase, in particular of short 22-mer DNA sequences. The underlying mechanism selects for complementarity, as it enriches sequences that tightly interact in the dense phase through base-pairing. Our mechanism also enables initially weakly biased pools to enhance their sequence bias or to replace the previously most abundant sequences as the cycles progress. Our findings provide an example of a selection mechanism that may have eased screening for auto-catalytic self-replicating oligonucleotides.

Prebiotic Astrochemistry from Astronomical Observations and Laboratory Spectroscopy.

The discovery of more than 200 gas-phase chemical compounds in interstellar space has led to the speculation that this nonterrestrial synthesis may play a role in the origin of life. These identifications were possible because of laboratory spectroscopy, which provides the molecular fingerprints for astronomical observations. Interstellar chemistry produces a wide range of small, organic molecules in dense clouds, such as NH2COCH3, CH3OCH3, CH3COOCH3, and CH2(OH)CHO. Carbon (C) is also carried in the fullerenes C60 and C70, which can preserve C-C bonds from circumstellar environments for future synthesis. Elusive phosphorus has now been found in molecular clouds, the sites of star formation, in the molecules PO and PN. Such clouds can collapse into solar systems, although the chemical/physical processing of the emerging planetary disk is uncertain. The presence of molecule-rich interstellar starting material, as well as the link to planetary bodies such as meteorites and comets, suggests that astrochemical processes set a prebiotic foundation.

On the origins of life's homochirality: Inducing enantiomeric excess with spin-polarized electrons.

Life as we know it is homochiral, but the origins of biological homochirality on early Earth remain elusive. Shallow closed-basin lakes are a plausible prebiotic environment on early Earth, and most are expected to have significant sedimentary magnetite deposits. We hypothesize that ultraviolet (200- to 300-nm) irradiation of magnetite deposits could generate hydrated spin-polarized electrons sufficient to induce enantioselective prebiotic chemistry. Such electrons are potent reducing agents that drive reduction reactions where the spin polarization direction can enantioselectively alter the reaction kinetics. Our estimate of this chiral bias is based on the strong effective spin-orbit coupling observed in the chiral-induced spin selectivity (CISS) effect, as applied to energy differences in reduction reactions for different isomers. In the original CISS experiments, spin-selective electron transmission through a monolayer of double-strand DNA molecules is observed at room temperature-indicating a strong coupling between molecular chirality and electron spin. We propose that the chiral symmetry breaking due to the CISS effect, when applied to reduction chemistry, can induce enantioselective synthesis on the prebiotic Earth and thus facilitate the homochiral assembly of life's building blocks.

Freeze-thaw cycles enable a prebiotically plausible and continuous pathway from nucleotide activation to nonenzymatic RNA copying.

Nonenzymatic template-directed RNA copying using chemically activated nucleotides is thought to have played a key role in the emergence of genetic information on the early Earth. A longstanding question concerns the number and nature of different environments that might have been necessary to enable all of the steps from nucleotide synthesis to RNA copying. Here we explore three sequential steps from this overall pathway: nucleotide activation, synthesis of imidazolium-bridged dinucleotides, and template-directed RNA copying. We find that all three steps can take place in one reaction mixture undergoing multiple freeze-thaw cycles. Recent experiments have demonstrated a potentially prebiotic methyl isocyanide-based nucleotide activation chemistry. However, the original version of this approach is incompatible with nonenzymatic RNA copying because the high required concentration of the imidazole activating group prevents the accumulation of the essential imidazolium-bridged dinucleotide. Here we report that ice eutectic phase conditions facilitate not only the methyl isocyanide-based activation of ribonucleotide 5'-monophosphates with stoichiometric 2-aminoimidazole, but also the subsequent conversion of these activated mononucleotides into imidazolium-bridged dinucleotides. Furthermore, this one-pot approach is compatible with template-directed RNA copying in the same reaction mixture. Our results suggest that the simple and common environmental fluctuation of freeze-thaw cycles could have played an important role in prebiotic nucleotide activation and nonenzymatic RNA copying.

Aqueous microdroplets enable abiotic synthesis and chain extension of unique peptide isomers from free amino acids.

Amide bond formation, the essential condensation reaction underlying peptide synthesis, is hindered in aqueous systems by the thermodynamic constraints associated with dehydration. This represents a key difficulty for the widely held view that prebiotic chemical evolution leading to the formation of the first biomolecules occurred in an oceanic environment. Recent evidence for the acceleration of chemical reactions at droplet interfaces led us to explore aqueous amino acid droplet chemistry. We report the formation of dipeptide isomer ions from free glycine or L-alanine at the air-water interface of aqueous microdroplets emanating from a single spray source (with or without applied potential) during their flight toward the inlet of a mass spectrometer. The proposed isomeric dipeptide ion is an oxazolidinone that takes fully covalent and ion-neutral complex forms. This structure is consistent with observed fragmentation patterns and its conversion to authentic dipeptide ions upon gentle collisions and for its formation from authentic dipeptides at ultra-low concentrations. It also rationalizes the results of droplet fusion experiments that show that the dipeptide isomer facilitates additional amide bond formation events, yielding authentic tri- through hexapeptides. We propose that the interface of aqueous microdroplets serves as a drying surface that shifts the equilibrium between free amino acids in favor of dehydration via stabilization of the dipeptide isomers. These findings offer a possible solution to the water paradox of biopolymer synthesis in prebiotic chemistry.

Human milk oligosaccharide 2'-fucosyllactose protects against high-fat diet-induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and faecal proteome profiles in mice.

OBJECTIVE: To decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2'-fucosyllactose (2'FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We wanted to elucidate whether 2'FL metabolic effects are linked with changes in intestinal mucus production and secretion, mucin glycosylation and degradation, as well as with the modulation of the gut microbiota, faecal proteome and endocannabinoid (eCB) system. RESULTS: 2'FL supplementation reduced HFD-induced obesity and glucose intolerance. These effects were accompanied by several changes in the intestinal mucus layer, including mucus production and composition, and gene expression of secreted and transmembrane mucins, glycosyltransferases and genes involved in mucus secretion. In addition, 2'FL increased bacterial glycosyl hydrolases involved in mucin glycan degradation. These changes were linked to a significant increase and predominance of bacterial genera Akkermansia and Bacteroides, different faecal proteome profile (with an upregulation of proteins involved in carbon, amino acids and fat metabolism and a downregulation of proteins involved in protein digestion and absorption) and, finally, to changes in the eCB system. We also investigated faecal proteomes from lean and obese humans and found similar changes observed comparing lean and obese mice. CONCLUSION: Our results show that the HMO 2'FL influences host metabolism by modulating the mucus layer, gut microbiota and eCB system and propose the mucus layer as a new potential target for the prevention of obesity and related disorders.

Proto-neural networks from thermal proteins.

Proteinoids are synthetic polymers that have structural similarities to natural proteins, and their formation is achieved through the application of heat to amino acid combinations in a dehydrated environment. The thermal proteins, initially synthesised by Sidney Fox during the 1960s, has the ability to undergo self-assembly, resulting in the formation of microspheres that resemble cells. These microspheres have fascinating biomimetic characteristics. In recent studies, substantial advancements have been made in elucidating the electrical signalling phenomena shown by proteinoids, hence showcasing their promising prospects in the field of neuro-inspired computing. This study demonstrates the advancement of experimental prototypes that employ proteinoids in the construction of fundamental neural network structures. The article provides an overview of significant achievements in proteinoid systems, such as the demonstration of electrical excitability, emulation of synaptic functions, capabilities in pattern recognition, and adaptability of network structures. This study examines the similarities and differences between proteinoid networks and spontaneous neural computation. We examine the persistent challenges associated with deciphering the underlying mechanisms of emergent proteinoid-based intelligence. Additionally, we explore the potential for developing bio-inspired computing systems using synthetic thermal proteins in forthcoming times. The results of this study offer a theoretical foundation for the advancement of adaptive, self-assembling electronic systems that operate using artificial bio-neural principles.

Prebiotic effect of galacto-N-biose on the intestinal lactic acid bacteria as enhancer of acetate production and hypothetical colonization.

Galacto-N-biose (GNB) is an important core structure of glycan of mucin glycoproteins in the gastrointestinal (GI) mucosa. Because certain beneficial bacteria inhabiting the GI tract, such as bifidobacteria and lactic acid bacteria, harbor highly specialized GNB metabolic capabilities, GNB is considered a promising prebiotic for nourishing and manipulating beneficial bacteria in the GI tract. However, the precise interactions between GNB and beneficial bacteria and their accompanying health-promoting effects remain elusive. First, we evaluated the proliferative tendency of beneficial bacteria and their production of beneficial metabolites using gut bacterial strains. By comparing the use of GNB, glucose, and inulin as carbon sources, we found that GNB enhanced acetate production in Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lactobacillus gasseri, and Lactobacillus johnsonii. The ability of GNB to promote acetate production was also confirmed by RNA-seq analysis, which indicated the upregulation of gene clusters that catalyze the deacetylation of N-acetylgalactosamine-6P and biosynthesize acetyl-CoA from pyruvate, both of which result in acetate production. To explore the in vivo effect of GNB in promoting acetate production, antibiotic-treated BALB/cA mice were administered with GNB with L. rhamnosus, resulting in a fecal acetate content that was 2.7-fold higher than that in mice administered with only L. rhamnosus. Moreover, 2 days after the last administration, a 3.7-fold higher amount of L. rhamnosus was detected in feces administered with GNB with L. rhamnosus than in feces administered with only L. rhamnosus. These findings strongly suggest the prebiotic potential of GNB in enhancing L. rhamnosus colonization and converting L. rhamnosus into higher acetate producers in the GI tract. IMPORTANCE: Specific members of lactic acid bacteria, which are commonly used as probiotics, possess therapeutic properties that are vital for human health enhancement by producing immunomodulatory metabolites such as exopolysaccharides, short-chain fatty acids, and bacteriocins. The long residence time of probiotic lactic acid bacteria in the GI tract prolongs their beneficial health effects. Moreover, the colonization property is also desirable for the application of probiotics in mucosal vaccination to provoke a local immune response. In this study, we found that GNB could enhance the beneficial properties of intestinal lactic acid bacteria that inhabit the human GI tract, stimulating acetate production and promoting intestinal colonization. Our findings provide a rationale for the addition of GNB to lactic acid bacteria-based functional foods. This has also led to the development of therapeutics supported by more rational prebiotic and probiotic selection, leading to an improved healthy lifestyle for humans.

Microbiome-modulating nutraceuticals ameliorate dyslipidemia in type 2 diabetes: A systematic review, meta-analysis, and meta-regression of clinical trials.

AIMS: Type 2 Diabetes is intrinsically linked to cardiovascular disease (CVD) via diabetic dyslipidemia, both of which remain global health concerns with annually increasing prevalence. Given the established links between gut microbiome dysbiosis and metabolic diseases, its modulation is an attractive target to ameliorate metabolic imbalances in such patients. There is a need to quantitively summarise, analyse, and describe future directions in this field. METHODS: We conducted a systematic review, meta-analysis, and meta-regression following searches in major scientific databases for clinical trials investigating the effect of pro/pre/synbiotics on lipid profile published until April 2022. Data were pooled using random-effects meta-analysis and reported as mean differences with 95% confidence intervals (CIs). PROSPERO No. CRD42022348525. RESULTS: Data from 47 trial comparisons across 42 studies (n = 2692) revealed that, compared to placebo/control groups, the administration of pro/pre/synbiotics was associated with statistically significant changes in total cholesterol (-9.97 mg/dL [95% CI: -15.08; -4.87], p < 0.0001), low-density lipoprotein (-6.29 mg/dL [95% CI: -9.25; -3.33], p < 0.0001), high-density lipoprotein (+3.21 mg/dL [95% CI: 2.20; 4.22], p < 0.0001), very-low-density lipoprotein (-4.52 mg/dL [95% CI: -6.36; -2.67], p < 0.0001) and triglyceride (-22.93 mg/dL [95% CI: -33.99; -11.87], p < 0.001). These results are influenced by patient characteristics such as age or baseline BMI, and intervention characteristics such as dosage and duration. CONCLUSIONS: Our study shows that adjunct supplementation with a subset of pro/pre/synbiotics ameliorates dyslipidemia in diabetic individuals and has the potential to reduce CVD risk. However, widespread inter-study heterogeneity and the presence of several unknown confounders limit their adoption in clinical practice; future trials should be designed with these in mind.

A Prebiotic Pathway to Nicotinamide Adenine Dinucleotide.

Enzymes play a fundamental role in cellular metabolism. A wide range of enzymes require the presence of complementary coenzymes and cofactors to function properly. While coenzymes are believed to have been part of the last universal ancestor (LUCA) or have been present even earlier, the syntheses of crucial coenzymes like the redox-active coenzymes flavin adenine dinucleotide (FAD) or nicotinamide adenine dinucleotide (NAD+) remain challenging. Here, we present a pathway to NAD+ under prebiotic conditions starting with ammonia, cyanoacetaldehyde, prop-2-ynal and sugar-forming precursors, yielding in situ the nicotinamide riboside. Regioselective phosphorylation and water stable light activated adenosine monophosphate derivatives allow for topographically and irradiation-controlled formation of NAD+. Our findings indicate that NAD+, a coenzyme vital to life, can be formed non-enzymatically from simple organic feedstock molecules via photocatalytic activation under prebiotically plausible early Earth conditions in a continuous process under aqueous conditions.

A Magnesium Binding Site And The Anomeric Effect Regulate The Abiotic Redox Chemistry Of Nicotinamide Nucleotides.

Nicotinamide adenine dinucleotide (NAD+) is a redox active molecule that is universally found in biology. Despite the importance and simplicity of this molecule, few reports exist that investigate which molecular features are important for the activity of this ribodinucleotide. By exploiting the nonenzymatic reduction and oxidation of NAD+ by pyruvate and methylene blue, respectively, we were able to identify key molecular features necessary for the intrinsic activity of NAD+ through kinetic analysis. Such features may explain how NAD+ could have been selected early during the emergence of life. Simpler molecules, such as nicotinamide, that lack an anomeric carbon are incapable of accepting electrons from pyruvate. The phosphate moiety inhibits activity in the absence of metal ions but facilitates activity at physiological pH and model prebiotic conditions by recruiting catalytic Mg2+. Reduction proceeds through consecutive single electron transfer events. Of the derivatives tested, including nicotinamide mononucleotide, nicotinamide riboside, 3-(aminocarbonyl)-1-(2,3-dihydroxypropyl)pyridinium, 1-methylnicotinamide, and nicotinamide, only NAD+ and nicotinamide mononucleotide would be capable of efficiently accepting and donating electrons within a nonenzymatic electron transport chain. The data are consistent with early metabolic chemistry exploiting NAD+ or nicotinamide mononucleotide and not simpler molecules.

Self-immolation Assisted Morphology Transformation of Prebiotic Lipidated-cationic Amino Acids: Electro-droplet Mediated C-C Coupling Reaction to Synthesize Macromolecules.

Compartmentalization protected biomolecules from the fluctuating environments of early Earth. Although contemporary cells mostly use phospholipid-based bilayer membranes, the utility of non-bilayer compartments was not ruled out during the prebiotic and modern eras. In the present study, we demonstrated the prebiotic synthesis of lipidated cationic amino acid-based amphiphiles [lauryl ester of lysine (LysL); ornithine (OrnL); and 2,4-diamino butyric acid (DabL)] using model dry-down reaction. These amphiphiles self-assemble into micellar membranes. However, the OrnL and DabL-based micelles undergo pH-responsive transformation to lipid droplet-like morphologies, a modelcompartment in the prebiotic Earth. These cationic droplets encapsulated prebiotic molecules (isoprene) and assisted electron transfer reaction to synthesize isoprenoid derivatives at primitive Earth conditions. The self-assembly of prebiotic amphiphiles, their transformation to droplet compartments, and droplet-assisted C-C bond formation reaction might have helped the evolution to synthesize various biomolecules required for the origin of life.

B-Group Vitamins as Potential Prebiotic Candidates: Their Effects on the Human Gut Microbiome.

In recent years, thousands of studies have demonstrated the importance of the gut microbiome for human health and its relationship with certain diseases. The search for new gut microbiome modulators has thus become an objective to beneficially alter the gut microbiome composition and/or metabolic activity, which may modify intestinal physiology. Growing evidence has shown that B-group vitamins might be considered as potential candidates as gut microbiome modulators. However, the relationship between the B-group vitamins and the gut microbiome remains largely unexplored. Studies have suggested that non-absorbed B-group vitamins administered orally can reach the distal intestine or even the colon where these vitamins may have potential health benefits for the host. Clinical trials supporting this effect are still limited. In this review, we discuss evidence regarding the modulatory effects of B-group vitamins on the gut microbiome with a focus on their potential role as prebiotic candidates.

Identifying Gut Microbiome Features that Predict Responsiveness Toward a Prebiotic Capable of Increasing Calcium Absorption: A Pilot Study.

Previously, we demonstrated that prebiotics may provide a complementary strategy for increasing calcium (Ca) absorption in adolescents which may improve long-term bone health. However, not all children responded to prebiotic intervention. We determine if certain baseline characteristics of gut microbiome composition predict prebiotic responsiveness. In this secondary analysis, we compared differences in relative microbiota taxa abundance between responders (greater than or equal to 3% increase in Ca absorption) and non-responders (less than 3% increase). Dual stable isotope methodologies were used to assess fractional Ca absorption at the end of crossover treatments with placebo, 10, and 20 g/day of soluble corn fiber (SCF). Microbial DNA was obtained from stool samples collected before and after each intervention. Sequencing of the 16S rRNA gene was used to taxonomically characterize the gut microbiome. Machine learning techniques were used to build a predictive model for identifying responders based on baseline relative taxa abundances. Model output was used to infer which features contributed most to prediction accuracy. We identified 19 microbial features out of the 221 observed that predicted responsiveness with 96.0% average accuracy. The results suggest a simplified prescreening can be performed to determine if a subject's bone health may benefit from a prebiotic. Additionally, the findings provide insight and prompt further investigation into the metabolic and genetic underpinnings affecting calcium absorption during pubertal bone development.

The gut microbiome in the fight against obesity: The potential of dietary factors.

Obesity as a global public health burden has experienced a drastic growing trend recently. The management of obesity is challenging because of its complex etiology, and various factors are involved in its development, such as genetic and environmental factors. Different approaches are available to treat and/or manage obesity, including diet, physical activity, lifestyle changes, medications, and surgery. However, some of these approaches have inherent limitations and are closely associated with adverse effects. Therefore, probing into a novel/safe approach to treat and/or manage obesity is of fundamental importance. One such approach gaining renewed interest is the potential role of gut microbiota in obesity and its effectiveness in treating this condition. However, there is a dearth of comprehensive compilation of data on the potential role of the gut microbiome in obesity, particularly regarding dietary factors as a therapeutic approach. Therefore, this review aims to provide an updated overview of the role of gut microbiota in obesity, further highlighting the importance of dietary factors, particularly diet, prebiotics, and probiotics, as potential complementary and/or alternative therapeutic options. Moreover, the association of gut microbiota with obese or lean individuals has also been discussed.

Evaluation of synbiotic combinations of commercial probiotic strains with different prebiotics in in vitro and ex vivo human gut microcosm model.

Exploring probiotics for their crosstalk with the host microbiome through the fermentation of non-digestible dietary fibers (prebiotics) for their potential metabolic end-products, particularly short-chain fatty acids (SCFAs), is important for understanding the endogenous host-gut microbe interaction. This study was aimed at a systematic comparison of commercially available probiotics to understand their synergistic role with specific prebiotics in SCFAs production both in vitro and in the ex vivo gut microcosm model. Probiotic strains isolated from pharmacy products including Lactobacillus sporogenes (strain not labeled), Lactobacillus rhamnosus GG (ATCC53103), Streptococcus faecalis (T-110 JPC), Bacillus mesentericus (TO-AJPC), Bacillus clausii (SIN) and Saccharomyces boulardii (CNCM I-745) were assessed for their probiotic traits including survival, antibiotic susceptibility, and antibacterial activity against pathogenic strains. Our results showed that the microorganisms under study had strain-specific abilities to persist in human gastrointestinal conditions and varied anti-infective efficacy and antibiotic susceptibility. The probiotic strains displayed variation in the utilization of six different prebiotic substrates for their growth under aerobic and anaerobic conditions. Their prebiotic scores (PS) revealed which were the most suitable prebiotic carbohydrates for the growth of each strain and suggested xylooligosaccharide (XOS) was the poorest utilized among all. HPLC analysis revealed a versatile pattern of SCFAs produced as end-products of prebiotic fermentation by the strains which was influenced by growth conditions. Selected synbiotic (prebiotic and probiotic) combinations showing high PS and high total SCFAs production were tested in an ex vivo human gut microcosm model. Interestingly, significantly higher butyrate and propionate production was found only when synbiotics were applied as against when individual probiotic or prebiotics were applied alone. qRT-PCR analysis with specific primers showed that there was a significant increase in the abundance of lactobacilli and bifidobacteria with synbiotic blends compared to pre-, or probiotics alone. In conclusion, this work presents findings to suggest prebiotic combinations with different well-established probiotic strains that may be useful for developing effective synbiotic blends.

On the exclusion of exponential autocatalysts by sub-exponential autocatalysts.

Selection among autocatalytic species fundamentally depends on their growth law: exponential species, whose number of copies grows exponentially, are mutually exclusive, while sub-exponential ones, whose number of copies grows polynomially, can coexist. Here we consider competitions between autocatalytic species with different growth laws and make the simple yet counterintuitive observation that sub-exponential species can exclude exponential ones while the reverse is, in principle, impossible. This observation has implications for scenarios pertaining to the emergence of natural selection.