Analysis & Summary

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  • Largest known archaeal genome
  • Striking array of metabolic and cellular capabilities
  • Significant expansion of iron ABC transporters multigene family suggests surprising ability to adapt to iron poor environments
  • Novel methyltransferases indicate possible undiscovered energy sources for methanogenesis
  • Single subunit CO dehydrogenase suggests possible non-methanogenic growth
  • Presence of cytochrome d oxidase raises possibility of O2- dependant respiration
  • Flagellin and two chemotaxis genes identified although motility never observed in any Methanosarcina spp.
  • Ratio of sensory transduction kinases and single domain response regulators suggests a different mode of action for archaeal two-component signaling systems than in bacteria
  • Presence of multiple TBPs and a single TFB allows unique opportunity for investigation archaeal protein translation
  • Striking array of cell surface proteins with homologies to metazoan cell adhesion surface receptors

The Genome

  • 5,751,492 nucleotides
  • 74% coding coverage
  • 4528 protein coding genes
    • 2226 (49%) assigned putative function
    • 908 (20%) conserved hypothetical proteins
    • 1390 (31%) predicted proteins
  • Largest known archaeon
  • Third largest fully sequenced prokaryote
  • 2x as large as Archaeoglobus fulgidus and Halobacterium
  • Over 3x as large as Methanococcus jannaschii and
    Methanobacterium thermoautotrophicum


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  • A form of anaerobic respiration using one-carbon compounds or acetate as electron acceptor
  • Three pathways:
    • Reduce CO2 to methane with electrons from H2 (red arrows)
    • Reduce one molecule of a one-carbon compound with electrons from oxidation of three additional molecules (green arrows)
    • Split acetate to CO and methyl with subsequent reduction of methyl group using electrons from oxidation of CO (blue arrows)


  • Redundancy in (A) one-carbon compound pathway and (B) acetate pathway indicates specialization for these compounds
  • “Extra” corrinoid and MT2 (methyltransferase) enzymes suggest undiscovered energy sources for methanogenesis
  • Presence of single subunit CO dehydrogenase genes (MA1309, MA3283) indicates surprising possibility of non-methanogenic growth (never before observed in a methanogen)

Flagella and Chemotaxis

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  • Motility has never been observed in any Methanosarcina species
  • One flagellin (fla) gene cluster identified
  • Two complete chemotaxis (che) gene clusters identified, one adjacent to the fla gene cluster
  • Motility under appropriate circumstances?

Signal Transduction

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  • Bacterial two-component systems consist of typically 1:1 ratios of signal transduction histidine kinases (HK) and response regulators (RR)
  • Bacterial response regulators contain both a receiver domain and an effector domain
  • M. acetivorans contains 50 HKs but only 18 RRs
  • 17 of the response regulators contain only the receiver domain
  • Re-examination of other sequenced archaea reveals similar patterns
  • Archaeal two-component systems thus appear to utilize a different mode of action than bacterial systems

Protein Transcription

  • Poorly understood in the Archaea
  • Minimal apparatus is a complex of:
    • archaeal TATA box binding protein (TBP)
    • archaeal transcription factor B (TFB)
    • archaeal RNA polymerase (RNAP)
  • 3 TBP identified
  • 1 TFB
  • First methanogen with multiple TBPs
  • First archaea with multiple TBPs and only a single TFB
  • Possibility of differential gene expression through formation of alternative TBP-TFB-RNAP complexes
  • Presence of single TFB provides unique opportunity for the investigation of the role of multiple TBPs independently of role of multiple TFBs

Multicellular Structures

  • Large number of genes for production of cell envelope and extracellular matrices
  • Greater number and diversity of surface layer proteins than in other archaea
  • Surface layer proteins contains domains with homology to metazoan cell adhesion proteins
  • PKD domain: found in proteins implicated in forming cysts in polycystic kidney disease
  • YVAN domains: found in many proteins including LDL receptors

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