Analysis & Summary

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

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)

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?

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

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

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
(click to view larger image)	(click to view larger image)