Last universal common ancestor

The last universal common ancestor is the hypothesized common ancestral cell population from which all subsequent life forms descend, including Bacteria, Archaea, and Eukarya. The cell had a lipid bilayer; it possessed the genetic code and ribosomes which translated from DNA or RNA to proteins. Although the timing of the LUCA cannot be definitively constrained, most studies suggest that the LUCA existed by 3.5 billion years ago, and possibly as early as 4.3 billion years ago or earlier. The nature of this point or stage of divergence remains a topic of research.
All earlier forms of life preceding this divergence and all extant organisms are generally thought to share common ancestry. On the basis of a formal statistical test, this theory of a universal common ancestry is supported in preference to competing multiple-ancestry hypotheses. The first universal common ancestor is a hypothetical non-cellular ancestor to LUCA and other now-extinct sister lineages.
Whether the genesis of viruses falls before or after the LUCA–as well as the diversity of extant viruses and their hosts–remains a subject of investigation.
While no fossil evidence of the LUCA exists, the detailed biochemical similarity of all current life makes its existence widely accepted by biochemists. Its characteristics can be inferred from shared features of modern genomes. These genes describe a complex life form with many co-adapted features, including transcription and translation mechanisms to convert information from DNA to mRNA to proteins.

Historical background

A phylogenetic tree directly portrays the idea of evolution by descent from a single ancestor. An early tree of life was sketched by Jean-Baptiste Lamarck in his Philosophie zoologique in 1809. Charles Darwin more famously proposed the theory of universal common descent through an evolutionary process in his book On the Origin of Species in 1859: "Therefore I should infer from analogy that probably all the organic beings which have ever lived on this earth have descended from some one primordial form, into which life was first breathed." The last sentence of the book begins with a restatement of the hypothesis:
By 1871, in another letter to Hooker, Darwin speculated on the natural origin of life itself, writing that life might have begun in a "warm little pond, with all sorts of ammonia and phosphoric salts, light, heat, electricity, etc., present", an early expression of abiogenesis.
The term "last universal common ancestor" or "LUCA" was first used in the 1990s for such a primordial organism.

Inferring LUCA's features

Biochemical mechanisms

While the anatomy of LUCA cannot be reconstructed with certainty, its biochemical mechanisms can be deduced and described in some detail, based on properties shared by currently living organisms as well as genetic analysis.
LUCA certainly had genes and a genetic code. Its genetic material was most likely DNA, so that it lived after the RNA world. The DNA was kept double-stranded by an enzyme, DNA polymerase, which recognises the structure and directionality of DNA. The integrity of the DNA was maintained by a group of repair enzymes including DNA topoisomerase. If the genetic code was based on dual-stranded DNA, it was expressed by copying the information to single-stranded RNA. The RNA was produced by a DNA-dependent RNA polymerase using nucleotides similar to those of DNA. It had multiple DNA-binding proteins, such as histone-fold proteins. The genetic code was expressed into proteins. These were assembled from 20 free amino acids by translation of a messenger RNA via a mechanism of ribosomes, transfer RNAs, and a group of related proteins.
Although LUCA was likely not capable of sexual interaction, gene functions were present that promoted the transfer of DNA between individuals of the population to facilitate genetic recombination. Homologous gene products that promote genetic recombination are present in bacteria, archaea and eukaryota, such as the RecA protein in bacteria, the RadA protein in archaea, and the Rad51 and Dmc1 proteins in eukaryota.
LUCA's functionality, and evidence for the early evolution of membrane-dependent biological systems, together suggest that LUCA was a cell with membranes. It contained a water-based cytoplasm enclosed by a lipid bilayer membrane; it reproduced by cell division. It tended to exclude sodium and concentrate potassium by means of specific ion transporters. The cell multiplied by duplicating all its contents followed by cellular division. The cell used chemiosmosis to produce energy. It also reduced CO₂ and oxidized H₂ via acetyl-thioesters.
By phylogenetic bracketing, analysis of its offspring groups, LUCA appears to have been a small, single-celled organism. It likely had a ring-shaped coil of DNA floating freely within the cell. Morphologically, it would likely not have stood out within a mixed population of small modern-day bacteria. The originator of the three-domain system, Carl Woese, stated that in its genetic machinery, the LUCA would have been a "simpler, more rudimentary entity than the individual ancestors that spawned the three ".
Because bacteria and archaea differ in their structure of phospholipids and cell wall, ion pumping, most proteins involved in DNA replication, and glycolysis, it is inferred that LUCA had a permeable membrane without an ion pump. The emergence of Na⁺/H⁺ antiporters likely led to the later evolution of impermeable membranes in eukaryotes, archaea, and bacteria. This would accord with LUCA's having made use of the natural geochemical proton gradient in its environment across a leaky membrane to provide it with energy. Cell walls, too, would have evolved later. Although LUCA likely had DNA, it is unknown if it could replicate DNA: as Weiss et al write, it "might just have been a chemically stable repository for RNA-based replication". It is likely that LUCA's permeable membrane was composed of archaeal lipids and bacterial lipids. Isoprenoids would have helped to stabilize LUCA's membrane in the surrounding extreme habitat.
LUCA's genome was likely similar in size to that of modern prokaryotes, encoding around 2,600 proteins, based on statistical inference using the probabilistic gene- and species-tree reconciliation algorithm ALE. It may have been an acetogen, respiring anaerobically, and may have had an early CAS-based anti-viral immune system. The inferred metabolic features are consistent with the early Earth hydrothermal systems with high concentrations of CO₂ and H₂.

An anaerobic thermophile

An alternative to the search for "universal" traits is to use genome analysis to identify phylogenetically ancient genes. This gives a picture of a LUCA that could live in a geochemically harsh environment and is like modern prokaryotes. Analysis of biochemical pathways implies the same sort of chemistry as does phylogenetic analysis.
File:LUCA systems and environment.svg|thumb|upright=2|LUCA systems and environment, including the Wood–Ljungdahl or reductive acetyl–CoA pathway to fix carbon, and most likely DNA complete with the genetic code and enzymes to replicate it, transcribe it to RNA, and translate it to proteins.
In 2016, Madeline C. Weiss and colleagues genetically analyzed 6.1 million protein-coding genes and 286,514 protein clusters from sequenced prokaryotic genomes representing many phylogenetic trees, and identified 355 protein clusters that were probably common to the LUCA. The results of their analysis are highly specific, though debated. They depict LUCA as "anaerobic, CO₂-fixing, H₂-dependent with a Wood–Ljungdahl pathway, N₂-fixing and thermophilic. LUCA's biochemistry was replete with FeS clusters and radical reaction mechanisms." The cofactors indicate "dependence upon transition metals, flavins, S-adenosyl methionine, coenzyme A, ferredoxin, molybdopterin, corrins and selenium. Its genetic code required nucleoside modifications and S-adenosylmethionine-dependent methylations." They show that methanogens and clostridia were basal, near the root of the phylogenetic tree, in the 355 protein lineages examined, and that the LUCA may therefore have inhabited an anaerobic hydrothermal vent setting in a geochemically active environment rich in H₂, CO₂, and iron, where ocean water interacted with hot magma beneath the ocean floor. It is inferred that LUCA grew from H₂ and CO₂ via the reverse incomplete Krebs cycle. Other metabolic pathways inferred in LUCA are the pentose phosphate pathway, glycolysis, and gluconeogenesis. Even if phylogenetic evidence may point to a hydrothermal vent environment for a thermophilic LUCA, this does not constitute evidence that the origin of life took place at a hydrothermal vent since mass extinctions may have removed previously existing branches of life.
File:Reduktiver Acetyl-CoA-Weg.png|thumb|upright=1.6|The LUCA used the Wood–Ljungdahl or reductive acetyl–CoA pathway to fix carbon, if it was an autotroph, or to respire anaerobically, if it was a heterotroph.
Weiss and colleagues write that "Experiments... demonstrate that... acetyl-CoA pathway formate, methanol, acetyl moieties, and even pyruvate arise spontaneously... from CO₂, native metals, and water", a combination present in hydrothermal vents.
An experiment shows that Zn²⁺, Cr³⁺, and Fe can promote 6 of the 11 reactions of an ancient anabolic pathway called the reverse Krebs cycle in acidic conditions which implies that LUCA might have inhabited either hydrothermal vents or acidic metal-rich hydrothermal fields.

Undersampled protein families

Some other researchers have challenged Weiss et al.'s 2016 conclusions. Sarah Berkemer and Shawn McGlynn argue that Weiss et al. undersampled the families of proteins, so that the phylogenetic trees were not complete and failed to describe the evolution of proteins correctly. There are two risks in attempting to attribute LUCA's environment from near-universal gene distribution. On the one hand, it risks misattributing convergence or horizontal gene transfer events to vertical descent; on the other hand, it risks misattributing potential LUCA gene families as horizontal gene transfer events. A phylogenomic and geochemical analysis of a set of proteins that probably traced to the LUCA show that it had K⁺-dependent GTPases and the ionic composition and concentration of its intracellular fluid was seemingly high K⁺/Na⁺ ratio,, Fe²⁺, CO²⁺, Ni²⁺, Mg²⁺, Mn²⁺, Zn²⁺, pyrophosphate, and which would imply a terrestrial hot spring habitat. It possibly had a phosphate-based metabolism. Further, these proteins were unrelated to autotrophy, suggesting that the LUCA had a Heterotrophic lifestyle and that its growth was dependent on organic matter produced by the physical environment.
The presence of the energy-handling enzymes CODH/acetyl-coenzyme A synthase in LUCA could be compatible with being an autotroph and with life as a mixotroph or heterotroph. Weiss et al. in 2018 replied that no enzyme defines a trophic lifestyle, and that heterotrophs evolved from autotrophs.
A 2024 study directly estimated the order in which amino acids were added into the genetic code from early protein domain sequences. A total of 969 protein domains were classified as present in LUCA, including 101 domain sequences that dated back to the even-older pre-LUCA communities. 88% of the protein domains annotated as LUCA or pre-LUCA were confirmed by Moody et al. 2024, by being associated with proteins that are more than 50% likely to be present in LUCA. It found that amino acids that bind metals, and those that contain sulphur, came early in the genetic code. The study suggests that sulphur metabolism and catalysis involving metals were important elements of life at the time of LUCA.