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The physiology and habitat of the last universal common ancestor


The concept of a last universal common ancestor of all cells (LUCA, or the progenote) is central to the study of early evolution and life's origin, yet information about how and where LUCA lived is lacking. We investigated all clusters and phylogenetic trees for 6.1 million protein coding genes from sequenced prokaryotic genomes in order to reconstruct the microbial ecology of LUCA. Among 286,514 protein clusters, we identified 355 protein families (0.1%) that trace to LUCA by phylogenetic criteria. Because these proteins are not universally distributed, they can shed light on LUCA's physiology. Their functions, properties and prosthetic groups 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. Its cofactors reveal dependence upon transition metals, flavins, S-adenosyl methionine, coenzyme A, ferredoxin, molybdopterin, corrins and selenium. Its genetic code required nucleoside modifications and S-adenosyl methionine-dependent methylations. The 355 phylogenies identify clostridia and methanogens, whose modern lifestyles resemble that of LUCA, as basal among their respective domains. LUCA inhabited a geochemically active environment rich in H2, CO2 and iron. The data support the theory of an autotrophic origin of life involving the Wood–Ljungdahl pathway in a hydrothermal setting.

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Figure 1: Phylogeny for LUCA's genes.
Figure 2: Taxonomic distribution of LUCA's genes grouped by functional categories.
Figure 3: LUCA reconstructed from genome data.
Figure 4: Methyl groups in conserved modified nucleosides and in anaerobic autotroph metabolism.


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The authors thank J. Baross and N. Lane for discussions. The authors acknowledge the Zentrum für Informations- und Medientechnologie (ZIM) of the Heinrich-Heine University for computational support and the European Research Council for funding (ERC AdG 666053 to W.F.M.).

Author information




M.C.W., F.L.S., S.N., M.R. and S.N.-S. performed the bioinformatics analysis. F.L.S. and N.M. carried out the functional classification of the protein families. All authors analysed and discussed the results. W.F.M., F.L.S. and S.N.-S. designed the research. M.C.W., F.L.S., S.N., N.M., S.N.-S. and W.F.M. wrote the paper.

Corresponding author

Correspondence to William F. Martin.

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The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary Figures 1-3, Supplementary Tables 1,3-6, legends for Supplementary Tables 2,7-9, Supplementary References (PDF 1698 kb)

Supplementary Table 2

Functional and taxonomic characterization of the 355 protein families potentially present in LUCA using a threshold of 25% global identity (XLSX 95 kb)

Supplementary Table 7

SAM-dependent enzymes (XLSX 32 kb)

Supplementary Table 8

Functional and taxonomic characterization of one-taxa-misplaced protein families (XLSX 34 kb)

Supplementary Table 9

Functional and taxonomic characterization of one-phyla-misplaced protein families (XLSX 34 kb)

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Weiss, M., Sousa, F., Mrnjavac, N. et al. The physiology and habitat of the last universal common ancestor. Nat Microbiol 1, 16116 (2016).

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