Is LUCA a thermophilic progenote?
Venue: Nature Microbiology

We wish to comment on several claims made in the paper by Weiss et al.1, which describes a genomic analysis that they believe is consistent with the origin of life and emergence of a progenote like last universal common ancestor (LUCA) in hydrothermal vent conditions. The hydrothermal vent concept was proposed by researchers in the 1980s as an ocean would have been the dominant aqueous medium on the early Earth. Most would also agree that life could not begin in the open ocean because there is no obvious source of free energy to drive energetically uphill processes, so when the vent idea was first proposed it was welcomed2. The vents provide an obvious source of free energy in the form of redox potentials and pH gradients, and their sponge like mineral structures could potentially serve as compartments. Furthermore, microbial life has adapted to vent conditions, so maybe it began there. Proponents adopted the idea and published numerous papers on the subject in the form of essays (for example, refs 3,4) The article begins by reinforcing the frequent misconception that the terms 'LUCA' and 'progenote' share the same definition. They do not. Carl Woese and George Fox put forward the hypothesis that LUCA (also known as the cenancestor or most recent common ancestor of all life) was a progenote, which they defined as an organism "still in the process of evolving the relationship between genotype and phenotype"5. Fourteen years ago, one of us wrote an entry for the Encyclopedia of Molecular Biology 6 discussing the relationship between the progenote and LUCA concepts. The conclusion reached at that time is still valid today: sequence data, including the data presented by Weiss et al. support the idea that LUCA was a prokaryotic cell using nucleic acids as genetic material, 20 genetically encoded amino acids, ribosomes for templatedirected protein synthesis, and membranes that allowed for chemiosmotic coupling7,8. To consider a cellular organism with these properties as only "half alive"1 reflects an uncommon definition of life. Weiss et al. propose a computational scheme that provides a shortcut to identify genes that may have been present in LUCA. This approach is subject to two types of error: False positives. The stated criterion1 for inclusion in the LUCA gene set is that the gene needs to be present in two archaeal and two bacterial groups. From the presented tables, it is clear that orders are considered as distinct groups. The criterion identifies a gene as present in LUCA if a single transdomain transfer occurred before the two 'groups' (that is, orders) in the receiving domain split, or if the transferred gene was subsequently transferred between the two groups. Given that gene transfer within domains occurs more frequently than transfer between domains9,10, a large number of false positives are expected under the implemented scheme. False negatives, which are likely to be an even bigger problem. The authors correctly assume that gene transfer between the domains has occurred. Consequently, many genes that were present in LUCA will not be inferred as present. ATP synthases11 and aminoacyl transfer RNA (tRNA) synthetases12 illustrate this point, because only one out of at least five ATP synthase subunits was part of the inferred LUCA set1, and only eight aminoacyl tRNA synthetases, whereas LUCA appears to have used the full complement of today's genetically encoded amino acids, and had a functional ATPase/ATP synthase.