The Theory of the Last Universal Common Ancestor LUCA

Theory_LUCA 1 Apl. Prof. Dr. Dr. K. Saalbach Geostrategy and Geopolitics Department 1 49069 Osnabrueck The Theory of the Last Universal Common Ancestor LUCA 02 February 2026 Summary This working paper provides a brief introduction to the Last Universal Common Ancestor LUCA and the potential biosafety implications. LUCA is the hypothetical precursor of all modern cells, i.e., the Archaea, the Prokaryotes and Eukaryotes (which are the common ancestor of bacteria, animals, fungi, and plants). LUCA’s properties and timeframe of existence are relevant for the past, i.e., the origin of life, but also for the future, i.e., the question whether the generation of completely synthetic life could be possible which would be a major biosafety issue. Currently, all modified and synthetic organisms including synthetic viruses could only be produced in already living environments (only life can create other life), i.e., there is a clear border between dead and living materials. In this decade, the LUCA research made substantial progress by utilizing rapidly growing genomic databases and enhanced analysis methods (computed molecular clock of gene development combined with evidence from microfossils). The generally accepted theory is that life started with interactions between ribonucleic acid (RNA) and amino acids which formed complexes for replication in a membrane, i.e., a physical border between cell and environment. This is also known as ‘RNA world’. Later, desoxyribonucleic acid (DNA) was integrated. Early eukaryotes integrated alphaproteobacteria into a permanent symbiosis (now as mitochondria in animals, chloroplasts in plants) which enhanced metabolism and allowed the development of multi-cellular organisms. However, in December 2025, a calculation of mutation rates showed that LUCA seemed to have existed already shortly after the creation of Earth and Moon which was caused by the collision of two proto-planets 4.5 billion years ago. Some researchers found hints that LUCA was already a quite complex organism with an early immune system against viruses. But as LUCA is the last cell, not the first one, additional time must be added for the appearance of the first universal common ancestor FUCA. But when adding this, there is very little to no time left (dependent on the mutation rate calculation) since creation of Earth and Moon. In 2025, experiments on the International Space Station ISS showed that Archaea, Fungi and Bacteria survived long-term exposure to open space. Even the space dust collected from the surface of the ISS contained biological objects. In addition, it was shown that non-enzymatic synthesis of peptides is possible in space. A study from 2025 found bacteria in ultra-sterile spacecraft-assembly NASA cleanrooms despite extreme conditions; another study that bacteria and their viruses and can adapt themselves to microgravity by co-evolution. These findings may indicate that biomolecules e.g., from asteroids could have enabled and accelerated the early phases of life on the young earth which was not protected by a thick atmosphere. Experiments to create synthetic cells were done with Mycoplasma mycoides which were engineered to minimal genome cells with the smallest possible genome that allows autonomous life and replication. These experiments showed that replication below a certain complexity almost completely stopped, i.e., no clues to a hypothetical simplified cell replication in an RNA world could be shown. However, the rapid advances of Artificial Intelligence (AI) in genome analysis and creation of natural and artificial proteins as well as the ability to analyze very large genomic data sets may bring a sudden breakthrough in the LUCA debate, both for the understanding of origin of life as well as for the complete synthesis of living cells which could cause major biosafety issues via infection, contamination, or misuse. Theory_LUCA 2 Content 1 The LUCA Theory .................................................................................................................................. 3 1.1 Introduction ................................................................................................................................... 3 1.2 The Concept of LUCA ..................................................................................................................... 3 1.2.1 The Early Earth ....................................................................................................................... 3 1.2.2 FUCA and LUCA ....................................................................................................................... 4 1.2.3 Recent findings ....................................................................................................................... 5 1.3 Minimal Genome Cells .................................................................................................................. 5 1.4 Findings in Outer Space ................................................................................................................. 6 1.5 Potential Impact of Artificial Intelligence ...................................................................................... 7 2 Summary ............................................................................................................................................... 7 3 References ............................................................................................................................................ 8 Theory_LUCA 3 1 The LUCA Theory 1.1 Introduction This working paper provides a brief introduction to the Last Universal Common Ancestor LUCA and the potential biosafety implications. The Last Universal Common Ancestor LUCA is the hypothetical precursor of all modern cells, i.e., the Archaea, the Prokaryotes and Eukaryotes (cells with a nucleus which are the common ancestor of bacteria, animals, fungi, and plants). LUCA’s properties and timeframe of existence are relevant for the past, i.e., the origin of life, but also for the future, i.e., the question whether the generation of completely synthetic life could be possible. Currently, all modified and synthetic organisms including synthetic viruses could only be produced in already living environments (only life can create other life), i.e., there is a clear border between dead and living materials. In this decade, the LUCA research made substantial progress by utilizing rapidly growing genomic databases and enhanced analysis methods. While a study from Delaye et al. in 2005 was based on 20 genomes 1 , an analysis of Tobiasson et al. 2026 could use the prok2311 database from the National Center for Biotechnology Information (NCBI) GenBank of 75 million prokaryotic protein sequences from 47,545 complete prokaryotic genomes and the EukProt v.3 with 30 million eukaryotic sequences from 993 species 2 . Originally, the search for potential LUCA genes and the age calculation was based on the search for common genes between the main lineages of life, the Archaea, Prokaryotes and Eukaryotes. The study of Moody et al. 2024 computed the probability that a given gene was present by comparing the emergence of genes and species (gene trees to species trees), the influence of common mutations researchers to get a probability for each gene to be part of LUCA 3 resulting in 399 gene families that encoded approximately 2451 to 2855 proteins 4 . Furthermore, the age was estimated by a molecular clock, where the rate at which mutations occur is estimated and then the number of mutations is counted determine how much time has passed 5 . But in addition, the clock was cross-checked against microfossils as the earliest potential traces of biological life on Earth to align the calculation with geological evidence 6 . 1.2 The Concept of LUCA 1.2.1 The Early Earth The solar system started with the formation of dust to small proto-planets caused by gravity. Approximately 4,510±10 million years ago, two proto-planets collided, the proto-Earth Tellus with a mars-like object called Theia 7 , a thesis which is supported by geological findings on Earth and Moon which were created by the collision. Geological evidence from minerals indicates that the Earth cooled down to a continental crust with oceans approximately 100 to 200 million years later 8 which means that life could be theoretically possible then 9 . The first era, the Hadean, continued until 4 billion years ago, followed by the Archean. 1 Delaye et al. 2024 2 Tobiasson et al. 2026 3 Lambert 2024 4 Goldman/Becerra 2024 5 Starr 2024 6 Moody et al. 2024, Neukamm 2024 7 Moody et al. 2024 8 Goldman/Becerra 2024, Lambert 2024 9 Goldman/Becerra 2024 Theory_LUCA 4 It was argued that life could not survive the Hadean because of the hypothetical Late Heavy Bombardment (LHB) approximately 3.7 to 3.9 billion years ago by asteroids and celestial bodies coming from the Tellus-Theia collision 10 . However, the timeframe of the LHB is unknown. 1.2.2 FUCA and LUCA The generally accepted theory is that life started with interactions between ribonucleic acid (RNA) and amino acids which formed complexes for replication in a membrane, i.e., a physical border between cell and environment. This is also known as ‘RNA world’. In the 1980ies, catalytic properties of RNA were discovered which led to the hypothesis of an RNA world 11 . In this world, RNA-based enzymes (ribozymes) started to bind amino acids which then resulted in the formation of RNA-protein complexes and the ability to replicate. Until today, all cells synthesize proteins with ribosomes (RNA-protein complexes) which may indicate that the First Universal Common Ancestor FUCA started with a kind of ribosome with an early Peptidyl Transferase Center PTC which connects amino acids to peptides and protein chains 12 . While this likely but hypothetical, there is growing evidence that at lease the Last Universal Common Ancestor LUCA already had ribosomes 13 . Some points must be taken into consideration: Maybe there was not one FUCA; LUCA may have emerged by horizontal gene transfer between early life forms 14 . Also, it unlikely that FUCA and LUCA were alone. LUCA was probably part of a larger ecosystem, but is the only cell where the successors survived until today, while other life forms did not. When and how viruses emerged is unknown. The most plausible hypothesis is that viruses emerged as spin-offs from very early life forms and since then exist in a never-ending coevolution with their host cells. It was speculated that retroviruses may then have introduced DNA into early cells which changed the RNA world into a DNA world. DNA has the evolutionary advantage of a higher stability than RNA. The findings of Moody et al. 2024, that LUCA already seemed to have a CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein) system to identify and remove viral sequences, supports the theory that viruses emerged before LUCA. The LUCA genome shows the importance of ribosomes, i.e., nucleic acid (RNA)-protein complexes which drive metabolism and form the link between genes and protein synthesis. Meanwhile it was shown that even today phosphorus-rich lakes exist which would be ideal for emergence of such cells 15 . In 1976, the researcher Woese analyzed ribosomal subunits and discovered the archaea as separate entity 16 . After decades of discussion there is meanwhile growing evidence from genome database analyses that LUCA developed to early bacteria and archaea and that eukaryotes emerged from the Asgard subgroup of archaea 17 . This subgroup integrated alphaproteobacteria into a permanent symbiosis (now as mitochondria in animals, chloroplasts 10 Moody et al. 2024 11 Prosdocimi et al. 2019 12 Prosdocimi et al. 2019 13 Moody et al. 2024 14 McClellan 2013, Delaye et al. 2024 15 University of Washington 2019 16 Prosdocimi et al. 2019 17 Tobiasson et al. 2026 Theory_LUCA 5 in plants) 18 which enhanced metabolism and allowed the development of multi-cellular organisms 19 . Figure 1 presents a simplified summary of the current theories. 1.2.3 Recent findings However, in December 2025, a calculation of mutation rates showed that LUCA seemed to have existed already shortly after the creation of Earth and Moon which was caused by the collision of two proto-planets 4.5 billion years ago. Moody et al. 2024 estimated that LUCA lived around 4.2 Ga, with a 95% confidence interval from 4.09 to 4.33 Ga. 20 Furthermore, they found hints that LUCA was already a quite complex organism with an early immune system against viruses. The estimated size of the LUCA genome with 399 gene families that encoded approximately 2451 to 2855 proteins shows an organism with a similar complexity to bacteria. In a new analysis from December 2025, Kay et al. calculated an even earlier timeframe of LUCA of 4.50 Ga with a confidence interval from 4.43 to 4.52 Ga) which would be directly after the proto-planet collision 21 . But as LUCA is the last cell, not the first one, additional time must be added for the appearance of the first universal common ancestor FUCA. But when adding this, there is very little to no time left (dependent on the mutation rate calculation) since creation of Earth and Moon. 1.3 Minimal Genome Cells Experiments to create synthetic cells were done with Mycoplasma mycoides which were engineered to minimal genome cells with the smallest possible genome that allows autonomous life and replication. However, these experiments showed that replication below a certain complexity almost completely stopped, i.e., no clues to a hypothetical simplified cell replication in an RNA world could be shown. The minimal genome is the smallest possible genome that allows autonomous life and selfreplication. Since 2010, Craig Venter and his team worked to develop a minimal genome cell 18 Kay et al. 2025 19 Tobiasson et al. 2026 assume that this process was supported by numerous but sporadic horizontal acquisitions of genes from other bacteria both before and after endosymbiosis. 20 Moody et al. 2024, Lambert 2024 In the LUCA publications, it is common practice to use Giga (Ga) instead of billions. 21 Kay et al. 2025, Figure 1 Theory_LUCA 6 (the first one was called JCVI-syn1.0 or ‘Synthia’ with 901 genes) 22 . Mycoplasma was the smallest known autonomous cell type and thus used as model organism since 1984. In 2016, a new cell, called JCVI-syn3.0, was created by replacing the genome of Mycoplasma capricolum with the genome of Mycoplasma mycoides 23 , with removal of unessential deoxyribonucleic acid (DNA). It had only 473 genes, but still the function of 149 genes was unknown 24 . After it was found that a slightly larger genome leads to improved cell growth, a modified minimal cell was created which allowed to reduce the number of genes with unknown function to 30 in the year 2019 25 . In 2021, a reverse genetics approach determined that seven genes are required together for normal cell division of the minimal cell and the addition of these seven genes for the new JCVI-syn3A resulted in a normal morphology while JCVI-syn3.0 was pleomorphic with a low replication rate 26 . A study from 2024 showed that Mycoplasma mycoides and its derived ‘minimal cell’ (JCVISyn3A) could exist with a very simple membrane which consisted of a two-component lipidome 27 . These results do not indicate that the RNA world hypothesis is wrong, but that replication with DNA seems to require a certain complexity and no clue to a simplified replication in the hypothetical RNA world could be found. Despite the research on artificial and synthetic cells, all modified and synthetic organisms including synthetic viruses could only be produced in already living environments (only life can create other life), i.e., there is a clear border between dead and living materials. 1.4 Findings in Outer Space In 2025, experiments on the International Space Station ISS showed that Archaea, Fungi and Bacteria survived long-term exposure to open space. The experiment named "Test" showed that after two-years exposure to open space, spore-forming bacteria of the species Bacillus subtilis, fungi of the species Aureobasidium pullulans and archaea of the species Methanosarcina mazei S-6T, deposited on cotton wool, survived with decreased numbers 28 . The dehydration and partial lyophilization in the space vacuum may have contributed to survival 29 . Even the space dust collected from the surface of the ISS contained biological objects 30 . “Test” was the first long-term full exposure to open space while other experiments ("ExposureE", "Exposure-R", "Biorisk", "Tanpopo") evaluated only partial aspects of space exposure 31 . Also, inside the ISS. The bacterium E. bugandensis was found which was different from terrestrial variants and was highly resistant against antibiotics by antibiotic target alteration, antibiotic efflux, reduced permeability to antibiotics, and antibiotic inactivation 32 . In addition, it was shown that non-enzymatic synthesis of peptides is possible in space 33 . A study from 2025 found bacteria in ultra-sterile spacecraft-assembly NASA cleanrooms despite 22 Wang/Zhang 2019 23 Further evaluations were done with Mycoplasma pulmonis, Mycoplasma pnemoniae and Mycoplasma genitalium, refer to Glass et al. 2017 24 Danchin/Fang 2016 25 Lachance et al. 2019 26 Pelletier et al. 2021 27 Justice et al. 2024 28 Deshevaya et al. 2024 29 Deshevaya et al. 2024 30 Deshevaya et al. 2024 31 Deshevaya et al. 2024 32 Caldwell 2024, Sengupta et al. 2024 33 Baum 2026, Hopkinson et al. 2026 Theory_LUCA 7 extreme conditions 34 ; another study that bacteria and their viruses and can adapt themselves to microgravity by co-evolution 35 . These findings may indicate that biomolecules e.g., from asteroids could have enabled and accelerated the early phases of life on the young earth which was not protected by a thick atmosphere. 1.5 Potential Impact of Artificial Intelligence However, the rapid advances of Artificial Intelligence (AI) in genome analysis and creation of natural and artificial proteins as well as the ability to analyze very large genomic data sets may bring a sudden breakthrough in the LUCA debate, both for the understanding of origin of life as well as for the complete synthesis of living cells. This could cause major safety issues, as these cells may cause infections or contaminate ecosystems. There is also a substantial risk of misuse. Already existing AI-enabled biological tools were meanwhile updated like the advanced protein structure analyzer AlphaFold-3 and the ChatGPT-like AI system Evo2. AlphaFold 3 can predict the structure of complexes including proteins, nucleic acids, small molecules, ions, and modified residues. 36 Technologies like AlphaFold could be repurposed to engineer pathogens 37 . Evo2 was trained on 9.3 trillion DNA base pairs and works with 40 billion parameters to predict the functional impacts of genetic variations from noncoding pathogenic mutations to clinically significant gene variants. In addition, Evo2 generates mitochondrial, prokaryotic, and eukaryotic sequences at genome scale 38 . Evo2 is a step towards designing completely new genomes 39 . 2 Summary This working paper provided a brief introduction to the Last Universal Common Ancestor LUCA and the potential biosafety implications. LUCA is the hypothetical precursor of all modern cells, i.e., the Archaea, the Prokaryotes and Eukaryotes (which are the common ancestor of bacteria, animals, fungi, and plants). In this decade, the LUCA research made substantial progress by utilizing rapidly growing genomic databases and enhanced analysis methods. The generally accepted theory is that life started with interactions between ribonucleic acid (RNA) and amino acids which formed complexes for replication in a membrane, i.e., a physical border between cell and environment. This is also known as ‘RNA world’. later, desoxyribonucleic acid (DNA) was integrated. Early eukaryotes integrated eukaryotes alphaproteobacteria into a permanent symbiosis (mitochondria in animals, chloroplasts in plants) which enhanced metabolism and allowed the development of multi-cellular organisms. However, in December 2025, a calculation of mutation rates showed that LUCA seemed to have existed already shortly after the creation of Earth and Moon which was caused by the collision of two proto-planets 4.5 billion years ago. Some researchers found hints that LUCA was already a quite complex organism with an early immune system against viruses. But as LUCA is the last cell, not the first one, additional time must be added for the appearance of the first universal common ancestor FUCA. But when adding this, there is very little to no time left (dependent on the mutation rate calculation) since creation of Earth and Moon. 34 Amazouz 2025, Schultz et al. 2025 35 Huss et al. 2026 36 Abramson et al. 2024 37 Haley/Burrell 2025 38 Brixi et al. 2025 39 Callaway 2025 Theory_LUCA 8 In 2025, experiments on the International Space Station ISS showed that Archaea, Fungi and Bacteria survived long-term exposure to open space. Even the space dust collected from the surface of the ISS contained biological objects. In addition, it was shown that non-enzymatic synthesis of Archaea peptides is possible in space. A study from 2025 found bacteria in ultrasterile spacecraft-assembly NASA cleanrooms despite extreme conditions; another study that bacteria and their viruses and can adapt themselves to microgravity by co-evolution. These findings may indicate that biomolecules e.g., from asteroids could have enabled and accelerated the early phases of life on the young earth which was not protected by a thick atmosphere. Experiments to create synthetic cells were done with Mycoplasma mycoides which were engineered to minimal genome cells with the smallest possible genome that allows autonomous life and replication. These experiments showed that replication below a certain complexity almost completely stopped, i.e., no clues to a hypothetical simplified cell replication in an RNA world could be shown. However, the rapid advances of Artificial Intelligence (AI) in genome analysis and creation of natural and artificial proteins as well as the ability to analyze very large genomic data sets may bring a sudden breakthrough in the LUCA debate, both for the understanding of origin of life as well as for the complete synthesis of living cells which could cause major biosafety issues via infection, contamination, or misuse. 3 References Abramson, J. et al. (2024): Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature, Vol 630, 13 June 2024, p.493 Amazouz, L. (2025): 26 Resilient Microbes Found In NASA Cleanrooms Spark New Fears Of Mars Contamination. Daily Galaxy December 30, 2025 Baum, S. (2026): Complex building blocks of life form spontaneously in space, research reveals. phys org Brixi, G. et al. (2025): Genome modeling and design across all domains of life with Evo 2. Arc Institute Paper 2025 Caldwell, S. 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