nucleation

THEORY-1109: Santana-Molina, Williams, Snel and Spang find that the last eukaryotic common ancestor's central carbon metabolism was chimeric: a few Asgard-archaeal enzymes in cytosolic glycolysis and the pentose phosphate pathway, four placed with Asgard archaea at bootstrap 39–97% and two ambiguously, most alphaproteobacterial ones in the mitochondrial TCA cycle and pyruvate conversion, and others from various bacteria with no third dominant donor, since remodelled by loss, horizontal replacement and retargeting so that compartment no longer follows origin; the authors take the cytosol–mitochondrion split as support for syntrophy

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Properties7
StatusActive
Version3
Tagsendosymbiosis, natural-sciences
SourceLIT-1564 — Chimeric origins and dynamic evolution of central carbon metabolism in eukaryotes
Bears onQUESTION-277 — When formerly autonomous partners come to depend on one another, which of mutual dependence, reproductive cohesion, the distribution of essential functions across genomes, the host's regulatory control and the alignment of selection does each route to dependence bring about, and which of them, alone or together, make the partnership a new evolutionary individual?
Cited as “extends” byTHEORY-1205 — Eukaryotes began in a syntrophic partnership: an archaeal host fermented sugars and passed reducing equivalents to an alphaproteobacterial endosymbiont that contributed a TCA cycle and an electron transport chain, which is why the last eukaryotic common ancestor's central carbon metabolism is archaeal in cytosolic glycolysis and the pentose phosphate pathway and alphaproteobacterial in the mitochondrial TCA cycle
Cited as “grounds” byCLAIM-506 — The split of the last eukaryotic common ancestor's central carbon metabolism, archaeal enzymes in the cytosol and alphaproteobacterial ones in the mitochondrion, does not single out syntrophy: a host that kept its own archaeal glycolysis and took up a bacterium with a TCA cycle leaves it whether the partnership began in syntrophy or by engulfment by an already complex host, and what the split counts against is a host whose carbon metabolism was replaced by the symbiont's

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Source

Santana-Molina, Williams, Snel & Spang (2025), Nature Ecology & Evolution 9(4): 613–627, LIT-1564, read in full in NOTE-1239 from the PubMed Central copy (PMC11976288). The Results, the Discussion, Methods, Figures 1–5 and Extended Data Figures 1–7, read from captions.

What was actually shown

  • LECA’s pathways. Putative LECA clades for nine of ten glycolytic steps, seven of eight pentose phosphate steps and all ten TCA steps, in 64 hand-curated gene-family trees.
  • Asgard enzymes. ADPGK (76% bootstrap), APGM (89%), enolase (39%) and RPIA (97%) nest with Asgard. GPMI and pyruvate kinase do so ambiguously. Except for enolase, they are patchily distributed today, “apparently because of independent horizontal replacement events”.
  • Alphaproteobacterial enzymes. Seventeen: two glycolytic (ALDO, TPI), one pentose phosphate (PRPS), four pyruvate dehydrogenase subunits and ten TCA enzymes. Most are mitochondrial. Some sister groups are mixed with Gammaproteobacteria.
  • Other donors. Individual well-supported trees point to Chlamydia, Planctomycetota–Verrucomicrobiota, Fusobacteriota, Dependentiae and Chloroflexota. “no additional dominant source of gene donations is apparent.”
  • Remodelling. Asgard-derived enzymes were replaced by bacterial ones in some lineages. Enzymes of non-alphaproteobacterial origin carry mitochondrial targeting signals, and some alphaproteobacterial ones do not. Plastid glycolysis comes mostly from duplicated host genes.
  • The reading. The split “is consistent with symbiogenetic models”. Then, more strongly: “Specifically, our results support the view of syntrophic interactions between host and endosymbiont”, the archaeon fermenting sugars and passing reducing equivalents to a bacterium “which contributed a TCA cycle and an electron transport chain”.

What could have failed: carbon metabolism could have been wholly bacterial, as earlier work proposed, and in four to six trees it is not. Asgard and alphaproteobacterial contributions could have been mixed across pathways and compartments. In the main they are not.

What this does not say

  • Not that syntrophy is singled out. Any model in which an archaeal host took up a bacterium with a TCA cycle predicts archaeal cytosolic enzymes and bacterial mitochondrial ones. That includes models where the host was already complex and took the bacterium up by engulfment. The authors list what would discriminate the models, “the types of metabolites exchanged, … the timing of mitochondrial acquisition, the mechanism of mitochondrial uptake”, and test none. The inference is mine.
  • Not that glycolysis is mainly Asgard. Glycolysis has Asgard enzymes, two alphaproteobacterial ones (ALDO, TPI) and several from other bacteria (HK, PFKA, GAPDH, PGK). The split describes where each partner’s contributions lie, not each pathway’s main origin.
  • Not that the host’s metabolism dominated. In this pathway set, alphaproteobacterial contributions outnumber Asgard ones by 17 to six.
  • Not that modern eukaryotes show the trace plainly. The trace is read from LECA’s reconstructed set. In living eukaryotes most Asgard enzymes have been replaced and targeting has drifted from origin.

Connections

  • THEORY-1104 (Tobiasson et al.): compatible, with a tension. Both find the alphaproteobacterial share centred on the mitochondrion. Tobiasson et al. find Asgard leading across most of metabolism, and this paper counts more alphaproteobacterial enzymes in carbon metabolism. The measures differ.
  • THEORY-1105 (Bernabeu et al.): compatible on the presence of the other donors, rival on their rank. The phyla Bernabeu et al. call major donors appear here as sisters to a few enzymes. This paper finds no third dominant donor. Sixty-four families is too few to rank donors, so the rivalry is weak. The two also differ on whether LECA had POR (PFO).
  • LIT-1597 (Martin & Müller 1998, unavailable). This paper sets its archaeal contributions against “the hypothesis that … the archaeal host metabolism was replaced by counterparts from the endosymbiont”, citing that work. On the paper’s evidence, the replacement was partial.
  • LIT-1591 (Imachi et al. 2020, read in NOTE-1238). Cited among the syntrophy models this paper supports.
  • QUESTION-277. It bears on G (functions split between partner genomes by origin, now all nuclear) and on C (host-derived enzymes imported into the mitochondrion). In plastids it suggests that host compensation may promote symbiont gene loss. It bears on D only through the syntrophy reading, which is inferred.

Note of 2026-10-30: promoted, and the wider thesis filed beside it

The twenty-second status review promoted this reading under ADR-065: it reports what Santana-Molina and colleagues find and how they read it, and NOTE-1239 read the paper in full. Whether eukaryotes began in a syntrophic partnership is THEORY-1205’s question, Proposed, which keeps this entry’s old promote_when. The record’s own critique, once in the title, is now CLAIM-506, Proposed.

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