Chimeric origins and dynamic evolution of central carbon metabolism in eukaryotes

Abstract

The origin of eukaryotes was a key event in the history of life. Current leading hypotheses propose that a symbiosis between an asgardarchaeal host cell and an alphaproteobacterial endosymbiont represented a crucial step in eukaryotic origin and that metabolic cross-feeding between the partners provided the basis for their subsequent evolutionary integration. A major unanswered question is whether the metabolism of modern eukaryotes bears any vestige of this ancestral syntrophy. Here we systematically analyse the evolutionary origins of the eukaryotic gene repertoires mediating central carbon metabolism. Our phylogenetic and sequence analyses reveal that this gene repertoire is chimeric, with ancestral contributions from Asgardarchaeota and Alphaproteobacteria operating predominantly in glycolysis and the tricarboxylic acid cycle, respectively. Our analyses also reveal the extent to which this ancestral metabolic interplay has been remodelled via gene loss, transfer and subcellular retargeting in the >2 billion years since the origin of eukaryotic cells, and we identify genetic contributions from other prokaryotic sources in addition to the asgardarchaeal host and alphaproteobacterial endosymbiont. Our work demonstrates that, in contrast to previous assumptions, modern eukaryotic metabolism preserves information about the nature of the original asgardarchaeal–alphaproteobacterial interactions and supports syntrophy scenarios for the origin of the eukaryotic cell. Analysis of the eukaryotic gene repertoires mediating central carbon metabolism identifies ancestral contributions from Alphaproteobacteria, Asgardarchaeota and other microbial taxa, followed by gene loss, transfer and subcellular retargeting, which have remodelled central carbon metabolism over time.