Editing Last universal common ancestor (section)

== Inferring LUCA's features ==

=== Biochemical mechanisms ===

While the anatomy of the LUCA cannot be reconstructed with certainty, its [[Metabolic pathway|biochemical mechanisms]] can be deduced and described in some detail, based on properties shared by currently living organisms as well as genetic analysis.<ref name="Wächtershäuser 1998">{{cite journal |last=Wächtershäuser |first=Günter |year=1998 |title=Towards a Reconstruction of Ancestral Genomes by Gene Cluster Alignment |journal=Systematic and Applied Microbiology |volume=21 |issue=4 |pages=473–474, IN1, 475–477 |doi=10.1016/S0723-2020(98)80058-1 |bibcode=1998SyApM..21N1475W }}</ref>

The LUCA certainly had [[gene]]s and a [[genetic code]].<ref name="Weiss Preiner Xavier 2018">{{cite journal |last1=Weiss |first1=Madeline C. |last2=Preiner |first2=Martina |last3=Xavier |first3=Joana C. |last4=Zimorski |first4=Verena |last5=Martin |first5=William F. |date=2018-08-16 |title=The last universal common ancestor between ancient Earth chemistry and the onset of genetics |journal=PLOS Genetics |volume=14 |issue=8 |pages=e1007518 |doi=10.1371/journal.pgen.1007518 |pmc=6095482 |pmid=30114187 |s2cid=52019935 |doi-access=free}}</ref> Its genetic material was most likely DNA,<ref name="Wächtershäuser 1998"/> so that it lived after the [[RNA world]].{{efn|Other studies propose that LUCA may have been defined wholly through [[RNA]],<ref>{{cite magazine |url=https://www.newscientist.com/article/mg21228404-300-life-began-with-a-planetary-mega-organism/ |title=Life began with a planetary mega-organism |last=Marshall |first=Michael |magazine=[[New Scientist]] |access-date=31 July 2016 |archive-url=https://web.archive.org/web/20160725170104/https://www.newscientist.com/article/mg21228404-300-life-began-with-a-planetary-mega-organism/ |archive-date=25 July 2016 |df=dmy-all |url-status=live}}</ref> consisted of a RNA-DNA hybrid genome, or possessed a retrovirus-like genetic cycle with DNA serving as a stable genetic repository.<ref>{{cite journal |last1=Koonin |first1=Eugene V. |author1-link=Eugene V. Koonin |last2=Martin |first2=William F. |author2-link=William F. Martin |date=1 December 2005 |df=dmy-all |title=On the origin of genomes and cells within inorganic compartments |journal=Trends in Genetics |volume=21 |issue=12 |pages=647–654 |doi=10.1016/j.tig.2005.09.006 |pmid=16223546 |pmc=7172762 }}</ref>}}<ref name="PiP">{{cite journal |last=Garwood |first=Russell J. |title=Patterns In Palaeontology: The first 3 billion years of evolution |year=2012 |journal=Palaeontology Online |volume=2 |issue=11 |pages=1–14 |url=http://www.palaeontologyonline.com/articles/2012/patterns-in-palaeontology-the-first-3-billion-years-of-evolution/ |access-date=June 25, 2015 |archive-url=https://web.archive.org/web/20150626104131/http://www.palaeontologyonline.com/articles/2012/patterns-in-palaeontology-the-first-3-billion-years-of-evolution/ |archive-date=June 26, 2015 |url-status=live }}</ref> The DNA was kept double-stranded by an [[enzyme]], [[DNA polymerase]], which recognises the structure and directionality of DNA.<ref>{{cite journal |last1=Koonin |first1=Eugene V. |author1-link=Eugene V. Koonin |last2=Krupovic |first2=M. |last3=Ishino |first3=S. |last4=Ishino |first4=Y. |title=The replication machinery of LUCA: common origin of DNA replication and transcription. |journal=BMC Biology |date=2020 |volume=18 |issue=1 |pages=61 |doi=10.1186/s12915-020-00800-9 |pmid=32517760 |pmc=7281927 |doi-access=free }}</ref> The integrity of the DNA was maintained by a group of [[DNA repair|repair]] enzymes including [[DNA topoisomerase]].<ref>{{Cite journal |last1=Ahmad |first1=Muzammil |last2=Xu |first2=Dongyi |last3=Wang |first3=Weidong |date=2017-05-23 |df=dmy-all |title=Type IA topoisomerases can be "magicians" for both DNA and RNA in all domains of life |journal=RNA Biology |volume=14 |issue=7 |pages=854–864 |doi=10.1080/15476286.2017.1330741 |pmc=5546716 |pmid=28534707 }}</ref> If the genetic code was based on [[Nucleic acid double helix|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<!--, with the exception that the DNA nucleotide [[thymidine]] was replaced by [[uridine]] in RNA-->.<ref name="Wächtershäuser 1998"/> It had multiple [[DNA-binding protein]]s, such as histone-fold proteins.<ref>{{Cite journal |last1=Lupas |first1=Andrei N. |last2=Alva |first2=Vikram |year=2018 |title=Histones predate the split between bacteria and archaea |journal=Bioinformatics |volume=35 |issue=14 |pages=2349–2353 |doi=10.1093/bioinformatics/bty1000 |pmid=30520969}}</ref> The genetic code was expressed into [[protein]]s. These were assembled from 20 free [[amino acid]]s by [[Translation (biology)|translation]] of a [[messenger RNA]] via a mechanism of [[ribosome]]s, [[transfer RNA]]s, and a group of related proteins.<ref name="Wächtershäuser 1998"/>

Although LUCA was likely not capable of [[sexual reproduction|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|Rad51]] and [[DMC1 (gene)|Dmc1]] proteins in eukaryota.<ref>Bernstein, H., Bernstein, C. (2017). Sexual Communication in Archaea, the Precursor to Eukaryotic Meiosis. In: Witzany, G. (eds) Biocommunication of Archaea. Springer, Cham. https://doi.org/10.1007/978-3-319-65536-9_7 {{Webarchive|url=https://web.archive.org/web/20240223213424/https://link.springer.com/chapter/10.1007/978-3-319-65536-9_7 |date=23 February 2024 }}</ref>

The functionality of LUCA as well as evidence for the early evolution of membrane-dependent biological systems together suggest that LUCA had cellularity and cell membranes.<ref>{{Cite journal |last1=Gogarten |first1=Johann Peter |last2=Taiz |first2=Lincoln |date=1992 |title=Evolution of proton pumping ATPases: Rooting the tree of life |url=http://dx.doi.org/10.1007/bf00039176 |journal=Photosynthesis Research |volume=33 |issue=2 |pages=137–146 |doi=10.1007/bf00039176 |pmid=24408574 |bibcode=1992PhoRe..33..137G |s2cid=20013957 |issn=0166-8595 |access-date=4 December 2023 |archive-date=23 February 2024 |archive-url=https://web.archive.org/web/20240223213452/https://link.springer.com/article/10.1007/BF00039176 |url-status=live }}</ref> As for the cell's structure, it contained a water-based [[cytoplasm]] effectively enclosed by a [[lipid bilayer]] membrane; it was capable of reproducing by cell division.<ref name="Wächtershäuser 1998"/> It tended to exclude [[sodium]] and concentrate [[potassium]] by means of specific [[Ion transporter|ion transporters]] (or ion pumps). The cell multiplied by duplicating all its contents followed by [[cellular division]]. The cell used [[chemiosmosis]] to produce energy. It also [[Redox|reduced]] CO<sub>2</sub> and oxidized H<sub>2</sub> ([[methanogenesis]] or [[acetogenesis]]) via [[acetyl]]-[[Thioester|thioesters]].<ref>{{cite journal |last1=Martin |first1=W. |last2=Russell |first2=M. J. |date=October 2007 |title=On the origin of biochemistry at an alkaline hydrothermal vent |journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences |volume=362 |issue=1486 |pages=1887–1925 |doi=10.1098/rstb.2006.1881 |pmc=2442388 |pmid=17255002}}</ref><ref>{{cite journal |last1=Lane |first1=Nick |author1-link=Nick Lane |last2=Allen |first2=J. F. |last3=Martin |first3=William |author3-link=William F. Martin |date=April 2010 |title=How did LUCA make a living? Chemiosmosis in the origin of life |journal=BioEssays |volume=32 |issue=4 |pages=271–280 |doi=10.1002/bies.200900131 |pmid=20108228}}</ref>

By [[phylogenetic bracketing]], analysis of the presumed LUCA's 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 [domains] (and their descendants)".<ref name="Woese Kandler Wheelis 1990">{{cite journal |last1=Woese |first1=C.R. |author1-link=Carl Woese |last2=Kandler |first2=O. |author-link2=Otto Kandler |last3=Wheelis |first3=M.L. |author-link3=Mark Wheelis |date=June 1990 |title=Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya |journal=PNAS |volume=87 |issue=12 |pages=4576–4579 |bibcode=1990PNAS...87.4576W |doi=10.1073/pnas.87.12.4576 |doi-access=free |pmc=54159 |pmid=2112744}}</ref> 

Because both bacteria and archaea have differences in the 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<sup>+</sup>/H<sup>+</sup> antiporters likely lead to the evolution of impermeable membranes present in eukaryotes, archaea, and bacteria. It is stated that "The late and independent evolution of glycolysis but not gluconeogenesis is entirely consistent with LUCA being powered by natural proton gradients across leaky membranes. Several discordant traits are likely to be linked to the late evolution of cell membranes, notably the cell wall, whose synthesis depends on the membrane and DNA replication".<ref name="Sojo Pomiankowski Lane 20142">{{Cite journal |last1=Sojo |first1=Víctor |last2=Pomiankowski |first2=Andrew |last3=Lane |first3=Nick |author3-link=Nick Lane |date=2014-08-12 |title=A Bioenergetic Basis for Membrane Divergence in Archaea and Bacteria |journal=PLOS Biology |volume=12 |issue=8 |pages=e1001926 |doi=10.1371/journal.pbio.1001926 |pmc=4130499 |pmid=25116890 |doi-access=free}}</ref> Although LUCA likely had DNA, it is unknown if it could replicate DNA and is suggested to "might just have been a chemically stable repository for RNA-based replication".<ref name="Weiss Preiner Xavier 2018"/> It is likely that the permeable membrane of LUCA was composed of archaeal lipids ([[isoprenoids]]) and bacterial lipids ([[Fatty acid|fatty acids]]). Isoprenoids would have enhanced stabilization of LUCA's membrane in the surrounding extreme habitat. Nick Lane and coauthors state that "The advantages and disadvantages of incorporating isoprenoids into cell membranes in different microenvironments may have driven membrane divergence, with the later biosynthesis of phospholipids giving rise to the unique G1P and G3P headgroups of archaea and bacteria respectively. If so, the properties conferred by membrane isoprenoids place the lipid divide as early as the [[origin of life]]".<ref name="Jordan Nee Lane 20192">{{Cite journal |last1=Jordan |first1=S. F. |last2=Nee |first2=E. |last3=Lane |first3=Nick |author3-link=Nick Lane |date=18 October 2019 |title=Isoprenoids enhance the stability of fatty acid membranes at the emergence of life potentially leading to an early lipid divide |journal=Interface Focus |volume=9 |issue=6 |doi=10.1098/rsfs.2019.0067 |pmc=6802135 |pmid=31641436}}{{Creative Commons text attribution notice|cc=by4|from this source=yes}}</ref>

A 2024 study suggests that LUCA's genome was similar in size to that of modern prokaryotes, coding for some 2,600 proteins; that it respired anaerobically, and was an [[acetogen]]; and that it had an early [[CRISPR|CAS]]-based anti-viral immune system.<ref name="Moody et al 2024"/>

=== An anaerobic thermophile ===

{{further|Phylogenetic bracketing}}

{{multiple image
|align             = center
|total_width       = 850
|image1            = Inferring LUCA's genome.svg
|caption1          = A direct way to infer LUCA's [[genome]] would be to find genes common to all surviving descendants, but little can be learnt by this approach, as there are only about 30 such genes. They are mostly for [[ribosome]] proteins, proving that LUCA had the [[genetic code]]. Many other LUCA genes have been lost in later lineages over 4 billion years of evolution.<ref name="Weiss Preiner Xavier 2018"/>
|image2            = Three ways to infer genes present in LUCA.jpg
|caption2          = Three ways to infer genes present in LUCA: universal presence, presence in both the [[Bacteria]]l and [[Archaea]]n domains, and presence in two [[Phylum|phyla]] in both domains. The first yields as stated only about 30 genes; the second, some 11,000 with [[Horizontal gene transfer|lateral gene transfer]] (LGT) very likely; the third, 355 genes probably in LUCA, since they were found in at least two phyla in both domains, making LGT an unlikely explanation.<ref name="Weiss Preiner Xavier 2018"/>
}}

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.<ref name="Weiss Preiner Xavier 2018"/>

[[File:LUCA systems and environment.svg|thumb|upright=2|LUCA systems and environment, including the [[Wood–Ljungdahl pathway|Wood–Ljungdahl or reductive acetyl–CoA pathway]] to [[Carbon fixation|fix carbon]], and most likely [[DNA]] complete with the [[genetic code]] and [[enzyme]]s to [[DNA replication|replicate]] it, [[Transcription (biology)|transcribe it to RNA]], and [[Translation (biology)|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 [[Prokaryote|prokaryotic]] genomes representing many [[Phylogenetic tree|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 organism|anaerobic]], [[Carbon dioxide|CO<sub>2</sub>]]-fixing, [[Hydrogen|H<sub>2</sub>]]-dependent with a [[Wood–Ljungdahl pathway]] (the reductive [[Acetyl-CoA|acetyl-coenzyme A]] pathway), [[Nitrogen|N<sub>2</sub>]]-fixing and [[Thermophile|thermophilic]]. LUCA's biochemistry was replete with [[Iron(II) sulfide|FeS]] clusters and [[Radical (chemistry)|radical]] reaction mechanisms."<ref name="Weiss et al 20162">{{cite journal |last1=Weiss |first1=Madeline C. |last2=Sousa |first2=F. L. |last3=Mrnjavac |first3=N. |last4=Neukirchen |first4=S. |last5=Roettger |first5=M. |last6=Nelson-Sathi |first6=S. |last7=Martin |first7=William F. |author7-link=William F. Martin |display-authors=3 |year=2016 |title=The physiology and habitat of the last universal common ancestor |url=http://complexityexplorer.s3.amazonaws.com/supplemental_materials/3.6+Early+Metabolisms/Weiss_et_al_Nat_Microbiol_2016.pdf |journal=Nature Microbiology |volume=1 |issue=9 |page=16116 |doi=10.1038/nmicrobiol.2016.116 |pmid=27562259 |s2cid=2997255 |access-date=10 October 2022 |archive-date=18 April 2022 |archive-url=https://web.archive.org/web/20220418220101/https://complexityexplorer.s3.amazonaws.com/supplemental_materials/3.6+Early+Metabolisms/Weiss_et_al_Nat_Microbiol_2016.pdf |url-status=live }}</ref> The [[Cofactor (biochemistry)|cofactors]] also reveal "dependence upon [[Transition metal|transition metals]], [[Flavin mononucleotide|flavins]], [[S-adenosyl methionine]], [[coenzyme A]], [[ferredoxin]], [[molybdopterin]], [[Corrin|corrins]] and [[selenium]]. Its genetic code required [[nucleoside]] modifications and S-adenosylmethionine-dependent [[Methylation|methylations]]."<ref name="Weiss et al 20162" /> They show that [[Methanogen|methanogenic]] [[Clostridium|clostridia]] were [[Basal (phylogenetics)|basal, near the root of the phylogenetic tree]], in the 355<!--yes, the same 355--> protein lineages examined, and that the LUCA may therefore have inhabited an anaerobic [[hydrothermal vent]] setting in a geochemically active environment rich in H<sub>2</sub>, CO<sub>2</sub>, and iron, where [[ocean]] water interacted with hot [[magma]] beneath the [[Seabed|ocean floor]].<ref name="Weiss et al 20162" /> It is even inferred that LUCA also grew from H<sub>2</sub> and CO<sub>2</sub> via the reverse incomplete Krebs cycle.<ref>{{Cite journal |last1=Harrison |first1=Stuart A. |last2=Palmeira |first2=Raquel Nunes |last3=Halpern |first3=Aaron |last4=Lane |first4=Nick |date=2022-11-01 |title=A biophysical basis for the emergence of the genetic code in protocells |journal=Biochimica et Biophysica Acta (BBA) - Bioenergetics |volume=1863 |issue=8 |pages=148597 |doi=10.1016/j.bbabio.2022.148597  |pmid=35868450 |doi-access=free}}</ref> Other metabolic pathways inferred in LUCA are the [[pentose phosphate pathway]], [[glycolysis]], and [[gluconeogenesis]].<ref>{{Cite journal |last1=Harrison |first1=Stuart A. |last2=Lane |first2=Nick |date=2018-12-12 |title=Life as a guide to prebiotic nucleotide synthesis |journal=Nature Communications |language=en |volume=9 |issue=1 |pages=5176 |bibcode=2018NatCo...9.5176H |doi=10.1038/s41467-018-07220-y |issn=2041-1723 |pmc=6289992 |pmid=30538225}}</ref> Even if phylogenetic evidence may point to a hydrothermal vent environment for a thermophilic LUCA, this does not constitute evidence that the [[Abiogenesis|origin of life]] took place at a hydrothermal vent since mass extinctions may have removed previously existing branches of life.<ref name="Cantine-2017" /> 

[[File:Reduktiver Acetyl-CoA-Weg.png|thumb|upright=1.6|The LUCA used the [[Wood–Ljungdahl pathway|Wood–Ljungdahl or reductive acetyl–CoA pathway]] to [[Carbon fixation|fix carbon]], if it was an [[autotroph]], or to [[Anaerobic respiration|respire anaerobically]], if it was a [[heterotroph]].]]

Weiss and colleagues write that "Experiments ... demonstrate that ... [[Wood–Ljungdahl pathway|acetyl-CoA pathway]] [chemicals used in anaerobic respiration] [[formate]], [[methanol]], [[Acetyl group|acetyl]] moieties, and even [[pyruvate]] arise spontaneously ... from CO<sub>2</sub>, native metals, and water", a combination present in hydrothermal vents.<ref name="Weiss Preiner Xavier 2018"/>

An experiment shows that Zn<sup>2+</sup>, Cr<sup>3+</sup>, 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.<ref>{{Cite journal |last1=Muchowska |first1=Kamila B. |last2=Varma |first2=Sreejith J. |last3=Chevallot-Beroux |first3=Elodie |last4=Lethuillier-Karl |first4=Lucas |last5=Li |first5=Guang |last6=Moran |first6=Joseph |date=2 October 2017 |title=Metals promote sequences of the reverse Krebs cycle |url=https://www.researchgate.net/publication/320171263 |journal=Nature Ecology & Evolution |volume=1 |issue=11 |pages=1716–1721 |doi=10.1038/s41559-017-0311-7 |issn=2397-334X |pmc=5659384 |pmid=28970480 |bibcode=2017NatEE...1.1716M }}</ref>

=== 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 (as in Weiss et al. 2016). On the one hand, it risks misattributing [[Convergent evolution|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<sup>+</sup>-dependent GTPases and the ionic composition and concentration of its intracellular fluid was seemingly high K<sup>+</sup>/Na<sup>+</sup> ratio, {{chem|NH|4|+}}, Fe<sup>2+</sup>, CO<sup>2+</sup>, Ni<sup>2+</sup>, Mg<sup>2+</sup>, Mn<sup>2+</sup>, Zn<sup>2+</sup>, pyrophosphate, and {{chem|PO|3-|4}} which would imply a terrestrial [[hot spring]] habitat. It possibly had a phosphate-based metabolism. Further, these proteins were unrelated to [[Autotroph|autotrophy]] (the ability of an organism to create its own [[organic matter]]), suggesting that the LUCA had a [[Heterotroph]]ic lifestyle (consuming organic matter) and that its growth was dependent on organic matter produced by the physical environment.<ref>{{Cite journal |last1=Mulkidjanian |first1=Armen Y. |last2=Bychkov |first2=Andrew Yu |last3=Dibrova |first3=Daria V. |last4=Galperin |first4=Michael Y. |last5=Koonin |first5=Eugene V. |author5-link=Eugene V. Koonin |year=2012 |title=Origin of first cells at terrestrial, anoxic geothermal fields |journal=[[Proceedings of the National Academy of Sciences of the United States of America|Proceedings of the National Academy of Sciences]] |volume=109 |issue=14 |pages=E821-30 |bibcode=2012PNAS..109E.821M |doi=10.1073/pnas.1117774109 |pmc=3325685 |pmid=22331915 |doi-access=free}}</ref> <!--[[Nick Lane]] argues that Na<sup>+</sup>/H<sup>+</sup> antiporters could readily explain the low concentration of Na<sup>+</sup> in the LUCA and its descendants.-->

The presence of the energy-handling enzymes [[CODH]]/[[Acetyl-CoA|acetyl-coenzyme A]] synthase in LUCA could be compatible not only with being an [[autotroph]] but also with life as a [[mixotroph]] or [[heterotroph]].<ref>{{cite journal |last1=Adam |first1=Panagiotis S. |last2=Borrel |first2=Guillaume |last3=Gribaldo |first3=Simonetta |date=6 February 2018 |title=Evolutionary history of carbon monoxide dehydrogenase/acetyl-CoA synthase, one of the oldest enzymatic complexes |journal=PNAS |volume=115 |issue=6 |pages=E1166–E1173 |bibcode=2018PNAS..115E1166A |doi=10.1073/pnas.1716667115 |pmc=5819426 |pmid=29358391 |doi-access=free}}</ref> Weiss et al. in 2018 replied that no enzyme defines a trophic lifestyle, and that heterotrophs evolved from autotrophs.<ref name="Weiss Preiner Xavier 2018"/>

A 2024 study directly estimated the order in which amino acids were added into the genetic code from early protein sequences. It found that amino acids that bind metals, and those that contain sulphur, came early in the sequence. The study suggests that sulphur metabolism and catalysis involving metals were important elements of life at the time of LUCA.<ref name="Wehbi Wheeler Morel 2024">{{cite journal |last1=Wehbi |first1=Sawsan |last2=Wheeler |first2=Andrew |last3=Morel |first3=Benoit |last4=Manepalli |first4=Nandini |last5=Minh |first5=Bui Quang |last6=Lauretta |first6=Dante S. |last7=Masel |first7=Joanna |author7link=Joanna Masel |title=Order of amino acid recruitment into the genetic code resolved by last universal common ancestor's protein domains |journal=Proceedings of the National Academy of Sciences |volume=121 |issue=52 |date=24 December 2024 |pages=e2410311121 |pmid=39665745 |pmc=11670089 |doi=10.1073/pnas.2410311121 |doi-access=free }}</ref>

=== Possibly a mesophile ===

Several lines of evidence suggest that LUCA was non-thermophilic. The content of G + C nucleotide pairs (compared to the occurrence of A + T pairs) can indicate an organism's thermal optimum as they are more thermally stable due to an additional hydrogen bond. As a result they occur more frequently in the rRNA of thermophiles; however this is not seen in LUCA's reconstructed rRNA.<ref>{{Cite journal |last1=Galtier |first1=Nicolas |last2=Tourasse |first2=Nicolas |last3=Gouy |first3=Manolo |date=1999-01-08 |title=A Nonhyperthermophilic Common Ancestor to Extant Life Forms |url=http://dx.doi.org/10.1126/science.283.5399.220 |journal=Science |volume=283 |issue=5399 |pages=220–221 |doi=10.1126/science.283.5399.220 |pmid=9880254 |access-date=4 December 2023 |archive-date=23 February 2024 |archive-url=https://web.archive.org/web/20240223213446/https://www.science.org/doi/10.1126/science.283.5399.220 |url-status=live }}</ref><ref>{{Cite journal |last1=Groussin |first1=Mathieu |last2=Boussau |first2=Bastien |last3=Charles |first3=Sandrine |last4=Blanquart |first4=Samuel |last5=Gouy |first5=Manolo |date=2013-10-23 |title=The molecular signal for the adaptation to cold temperature during early life on Earth |journal=Biology Letters |volume=9 |issue=5 |pages=20130608 |doi=10.1098/rsbl.2013.0608 |doi-access=free |pmid=24046876 |pmc=3971708 }}</ref><ref name="Cantine-2017">{{Cite journal |last1=Cantine |first1=Marjorie D. |last2=Fournier |first2=Gregory P. |date=2017-07-06 |title=Environmental Adaptation from the Origin of Life to the Last Universal Common Ancestor |url=http://dx.doi.org/10.1007/s11084-017-9542-5 |journal=Origins of Life and Evolution of Biospheres |volume=48 |issue=1 |pages=35–54 |doi=10.1007/s11084-017-9542-5 |pmid=28685374 |hdl=1721.1/114219 |s2cid=254888920 |hdl-access=free |access-date=4 December 2023 |archive-date=23 February 2024 |archive-url=https://web.archive.org/web/20240223213446/https://link.springer.com/article/10.1007/s11084-017-9542-5 |url-status=live }}</ref>

The identification of thermophilic genes in the LUCA has been challenged,<ref name="GogartenDeamer20162">{{cite journal |last1=Gogarten |first1=Johann Peter |last2=Deamer |first2=David |year=2016 |title=Is LUCA a thermophilic progenote? |url=https://zenodo.org/record/895471 |journal=Nature Microbiology |volume=1 |issue=12 |pages=16229 |doi=10.1038/nmicrobiol.2016.229 |pmid=27886195 |s2cid=205428194 |access-date=25 June 2019 |archive-date=3 April 2020 |archive-url=https://web.archive.org/web/20200403040656/https://zenodo.org/record/895471 |url-status=live }}</ref> as they may instead represent genes that evolved later in archaea or bacteria, then migrated between these via [[horizontal gene transfer]], as in Woese's 1998 hypothesis.<ref>{{cite journal |last=Woese |first=Carl |author-link=Carl Woese |date=June 1998 |title=The universal ancestor |journal=PNAS |volume=95 |issue=12 |pages=6854–6859 |bibcode=1998PNAS...95.6854W |doi=10.1073/pnas.95.12.6854 |pmc=22660 |pmid=9618502 |doi-access=free}}</ref> For instance, the thermophile-specific topoisomerase, [[reverse gyrase]], was initially attributed to LUCA<ref name="Weiss et al 20162" /> before an exhaustive phylogenetic study revealed a more recent origin of this enzyme followed by extensive horizontal gene transfer.<ref>{{Cite journal |last1=Catchpole |first1=Ryan J |last2=Forterre |first2=Patrick |date=2019-12-01 |title=The Evolution of Reverse Gyrase Suggests a Nonhyperthermophilic Last Universal Common Ancestor |url=https://academic.oup.com/mbe/article/36/12/2737/5545984 |journal=Molecular Biology and Evolution |volume=36 |issue=12 |pages=2737–2747 |doi=10.1093/molbev/msz180 |pmc=6878951 |pmid=31504731}}</ref> LUCA could have been a mesophile that fixed CO<sub>2</sub> and relied on H<sub>2</sub>, and lived close to hydrothermal vents.<ref>{{Cite journal |last1=Camprubí |first1=E. |last2=de Leeuw |first2=J. W. |last3=House |first3=C. H. |last4=Raulin |first4=F. |last5=Russell |first5=M. J. |last6=Spang |first6=A. |last7=Tirumalai |first7=M. R. |last8=Westall |first8=F. |date=2019-12-12 |title=The Emergence of Life |journal=Space Science Reviews |volume=215 |issue=8 |pages=56 |bibcode=2019SSRv..215...56C |doi=10.1007/s11214-019-0624-8 |doi-access=free}}</ref>

Further evidence that LUCA was [[Mesophile|mesophilic]] comes from the amino acid composition of its proteins. The abundance of I, V, Y, W, R, E, and L amino acids (denoted IVYWREL) in an organism's proteins is correlated with its optimal growth temperature.<ref>{{Cite journal |last1=Zeldovich |first1=Konstantin B |last2=Berezovsky |first2=Igor N. |last3=Shakhnovich |first3=Eugene I. |date=2007 |title=Protein and DNA Sequence Determinants of Thermophilic Adaptation |journal=PLOS Computational Biology |volume=3 |issue=1 |pages=e5 |doi=10.1371/journal.pcbi.0030005 |pmid=17222055 |pmc=1769408 |arxiv=q-bio/0607004 |bibcode=2007PLSCB...3....5Z |doi-access=free }}</ref> According to phylogenetic analysis, the IVYWREL content of LUCA's proteins suggests its ideal temperature was below 50°C.<ref name="Cantine-2017"/>

Evidence that bacteria and archaea both independently underwent phases of increased and subsequently decreased thermo-tolerance suggests a dramatic post-LUCA climate shift that affected both populations and would explain the seeming genetic pervasiveness of thermo-tolerant genetics.<ref>{{Cite journal |last1=Boussau |first1=Bastien |last2=Blanquart |first2=Samuel |last3=Necsulea |first3=Anamaria |last4=Lartillot |first4=Nicolas |last5=Gouy |first5=Manolo |date=2008-11-26 |title=Parallel adaptations to high temperatures in the Archaean eon |url=http://dx.doi.org/10.1038/nature07393 |journal=Nature |volume=456 |issue=7224 |pages=942–945 |doi=10.1038/nature07393 |pmid=19037246 |bibcode=2008Natur.456..942B |s2cid=4348746 |access-date=4 December 2023 |archive-date=23 February 2024 |archive-url=https://web.archive.org/web/20240223213509/https://www.nature.com/articles/nature07393 |url-status=live }}</ref>