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Updated: Jun 16, 2026

Adaptation at the Extremes of Life: Experimental Evolution with the Extremophile Archaeon Sulfolobus acidocaldarius
Published on: June 14, 2024
An archaeal order with multiple minichromosome maintenance genes
Alison D Walters1, James P J Chong1
1Department of Biology (Area 5), PO Box 373, University of York, York YO10 5YW, UK.
Abstract:
In eukaryotes, a complex of six highly related minichromosome maintenance (MCM) proteins is believed to function as the replicative helicase. Until recently, systems for exploring the molecular mechanisms underlying eukaryotic MCM function have been biochemically intractable. To overcome this, molecular studies of MCM function have been carried out using MCM homologues from the archaea. Archaeal MCM systems studied to date possess a single functional MCM, which forms a homohexameric complex that displays DNA binding, ATPase and helicase activities. We have identified an archaeal order that possesses multiple MCM homologues. blast searches of available Methanococcales genomes reveal that members of this order possess between two and eight MCM homologues. Phylogenetic analysis suggests that an ancient duplication in the Methanococcales gave rise to two major groups of MCMs. One group contains Methanococcus maripaludis S2 McmD and possesses a conserved C-terminal insert similar to one observed in eukaryotic MCM3, while the other group contains McmA, -B and -C. Analysis of the genome context of MCMs in the latter group indicates that these genes could have arisen from phage-mediated events. When co-expressed in Escherichia coli, the four MCMs from M. maripaludis co-purify, indicating the formation of heteromeric complexes in vitro. The presence of homologues from both groups in all Methanococcales indicates that there could be functionally important differences between these proteins and that Methanococcales MCMs may therefore provide an interesting additional model for eukaryotic MCM function.
Insights
Researchers discovered multiple minichromosome maintenance (MCM) proteins in archaea, suggesting complex MCM assemblies may be ancient. These findings offer new models for studying eukaryotic DNA replication helicase function.
Area of Science:
- Molecular Biology
- Genomics
- Biochemistry
Background:
- Eukaryotic DNA replication relies on a six-protein minichromosome maintenance (MCM) complex functioning as the replicative helicase.
- Studying eukaryotic MCM function has been challenging due to biochemical intractability, leading to research on archaeal homologues.
- Previously studied archaeal MCM systems feature a single MCM protein forming a homohexamer with DNA binding, ATPase, and helicase activities.
Purpose of the Study:
- To investigate the presence and potential function of multiple MCM homologues in archaea.
- To explore the evolutionary origins and assembly of MCM complexes in the Methanococcales order.
- To establish Methanococcales MCMs as a novel model system for understanding eukaryotic MCM function.
Main Methods:
- Bioinformatic analysis, including BLAST searches, of Methanococcales genomes to identify MCM homologues.
- Phylogenetic analysis to determine the evolutionary relationships between identified MCM proteins.
- Heterologous co-expression of Methanococcus maripaludis MCMs in Escherichia coli, followed by co-purification to assess complex formation.
Main Results:
- Multiple MCM homologues (two to eight) were identified across Methanococcales genomes.
- Phylogenetic analysis revealed two distinct groups of MCMs in Methanococcales, suggesting an ancient duplication event.
- Co-expression and co-purification demonstrated that four MCMs from M. maripaludis can form heteromeric complexes in vitro.
Conclusions:
- The Methanococcales possess multiple, distinct MCM proteins, unlike previously studied archaeal systems.
- The presence of different MCM groups suggests potential functional specialization and the possibility of complex heteromeric assemblies.
- Methanococcales MCMs represent a valuable new model for dissecting the molecular mechanisms of eukaryotic MCM helicase function.
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