"Cell-First" Hypothesis

Bacterial Microcompartments (BMCs)
Carboxysomes
Metabolosomes
Icosahedron Capsid

"Cell-First" Hypothesis for Icosahedral Structures

The traditional "cell-first" hypothesis in the context of the origin of life posits that cells predated viruses, which then evolved as parasites. The specific hypothesis mentioned in the query extends this idea to the structural components of certain bacterial microcompartments (BMCs), which are protein-bound organelles resembling viral capsids.

Implication for Viral Evolution: This finding supports the broader "cell-first" perspective that many major viral structural proteins may have been recruited from existing cellular proteomes, rather than evolving independently in a "virus-first" scenario.

This hypothesis suggests that a complex, self-assembling, icosahedral protein structure can evolve within a cellular context from existing cellular components, challenging the notion that such complex structures are exclusively or originally viral in nature.

PII signaling protein: This ubiquitous cellular protein is the ancestor of the major hexamer-forming BMC-H proteins.

Just as BMCs repurposed PII and OB-fold proteins, many viral capsid proteins are believed to have originated from cellular enzymes or signaling proteins that were co-opted to protect and deliver genetic material.

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Microcompartments in archaeal ancestors of eukaryotes: a
bioenergetic engine that could have fuelled eukaryogenesis

https://www.biorxiv.org/content/10.1101/2025.11.08.687404v2.full

Cellular origin of the viral capsid-like bacterial microcompartments

https://pmc.ncbi.nlm.nih.gov/articles/PMC5683377/

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Novel archaeal microcompartments (AMCs) in Hodarchaeales (close relatives to eukaryotes) that acted as "bioenergetic engines," boosting energy (NADH) production via sugar metabolism by concentrating enzymes and substrates, potentially fueling the evolution of the complex eukaryotic cell (eukaryogenesis) by enhancing nutrient capture and energy yield before the mitochondrial event.

These bacterial-derived structures, acquired through horizontal gene transfer, allowed for metabolic specialization, including DNA capture, providing an evolutionary advantage for the archaeal host.

Key Findings:
Discovery: QxMD Read discovered AMCs in Hodarchaeales, an order of Asgard archaea, the closest known archaeal relatives to eukaryotes.

Origin: These catabolic AMCs, specialized for sugar-phosphate metabolism, were acquired from deep-rooted bacteria via horizontal gene transfer (HGT).

Structure: Like bacterial microcompartments (BMCs), they have protein shells (pentamers hexamers) that enclose enzymes, but uniquely, their shells fuse with DNA-binding regions to scavenge cytosolic DNA.

Function (Bioenergetic Engine):
Colocalizing enzymes and channeling substrates within the AMC significantly boosts the flux of NADH (a key energy carrier), potentially by 100-fold, increasing cellular energy production.

This increased energy and nutrient scavenging capacity could have primed the archaeal host for the massive energetic demands of eukaryogenesis.

Significance for Eukaryogenesis:
Metabolic Advantage: Provided an internal "engine" for efficient energy production and substrate utilization in the archaeal host.

Nutrient Scavenging: Enabled capture of cytosolic DNA, offering another source of nutrients.

Evolutionary Precursor: Suggests that advanced internal compartmentalization, often seen as a hallmark of eukaryotes, had roots in archaeal ancestors, potentially paving the way for the later development of complex eukaryotic organelles.