The physiology and habitat of the last universal common ancestor

Madeline C. Weiss, Filipa L. Sousa, Natalia Mrnjavac, Sinje Neukirchen, Mayo Roettger, Shijulal Nelson-Sathi, William F. Martin

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.