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Last universal common ancestor
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=== 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>
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