An archaeal origin of the Wood-Ljungdahl H4MPT branch and the emergence of bacterial methylotrophy

Abstract

The tetrahydromethanopterin (H₄MPT) methyl branch of the Wood-Ljungdahl pathway is shared by archaeal and bacterial metabolisms that greatly contribute to the global carbon budget and greenhouse gas fluxes: methanogenesis and methylotrophy, including methanotrophy^1-3. It has been proposed that the H₄MPT branch dates back to the last universal common ancestor^4-6. Interestingly, it has been identified in numerous recently sequenced and mostly uncultured non-methanogenic and non-methylotrophic archaeal and bacterial lineages, where its function remains unclear^5,7. Here, we have examined the distribution and phylogeny of the enzymes involved in the H₄MPT branch and the biosynthesis of its cofactors in over 6,400 archaeal and bacterial genomes. We find that a full Wood-Ljungdahl H₄MPT pathway is widespread in Archaea and is likely ancestral to this domain, whereas this is not the case for Bacteria. Moreover, the inclusion of recently sequenced lineages leads to an important shortening of the branch separating Archaea and Bacteria with respect to previous phylogenies of the H₄MPT branch. Finally, the genes for the pathway are colocalized in many of the recently sequenced archaeal lineages, similar to bacteria. Together, these results weaken the last universal common ancestor hypothesis and rather favour an origin of the H₄MPT branch in Archaea and its subsequent transfer to Bacteria. We propose a scenario for its potential initial role in the first bacterial recipients and its evolution up to the emergence of aerobic methylotrophy. Finally, we discuss how an ancient horizontal transfer not only triggered the emergence of key metabolic processes but also important transitions in Earth's history.