Nature Microbiology

Snapshot: Dr. Patrick Forterre

Dr. Patrick Forterre of the Institut Pasteur in France shares his experiences in working with Archaea.

Go to the profile of Claudio Nunes-Alves
Nov 01, 2017
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Name: Dr. Patrick Forterre

Institution: Institut Pasteur

Location: Paris, France



Twitter: @PatrickForterre

Tell me a bit about how you came to be interested in Archaea and what your work entails.

I discovered Archaea by reading the review that Carl Woese wrote in Scientific American in 1981 describing his discovery of “archaebacteria”. I was working on DNA replication and DNA topoisomerase in E. coli, and decided to shift to Archaea. This led to our discovery of reverse gyrase, which is the only protein specific for thermophiles, and of a new family of type II DNA topoisomerase, Topo IIB. We also identified the archaeal chromosomal origin of replication and initiator proteins. I was fascinated by the discovery of unique viruses in Archaea by Wolfram Zillig in the eighties. In 2004, I set up a research unit to study these viruses with David Prangishvili. More recently, I have been working on membrane vesicles and nanopods produced by hyperthermophilic archaea of the order Thermococcales and their role in cell physiology. My reading of Carl Woese’s papers make me aware of the importance of questions such as the nature of the last universal common ancestor (LUCA), the topology of the tree of life and the origin of eukaryotes. In 2008, we proposed a third major archaeal phylum, Thaumarchaeota, and more recently, we obtained a robust tree of life supporting the monophyly of Archaea (including Asgards) based on the RNA polymerase phylogeny.

Looking back at the last 40 years, what would you describe as the most exciting areas of research linked to the study of the Archaea? And where do you see the field headed in the next decade?

Studying the molecular biology of archaea has been immensely rewarding by proving new perspectives to understand the molecular biology of Eukaryotes. For instance, it was widely believed that the complexity of eukaryotic RNA polymerases testified for the complexity of eukaryotes compared to procaryotes. The work of Wolfram Zillig revealed that this was not the case since archaeal RNA polymerases are as complex as eukaryotic ones. The discovery of archaeal Topo IIB allowed identifying the protein, SPO11, that initiates meiotic recombination and the plant Topo IIB that determines plant size via endoreduplication. This revealed an evolutionary link between Archaea, the origin of sex, and the size of our forests!

Molecular biology seems more diverse in Archaea than in the other two domains and it appears important now to study more model diverse ones, especially when cultivated organisms from novel described phyla will become available. Studying at the molecular level the interactions between the many new lineages of nanosized archaea and their hosts should become a really exciting new research area in the future.

The study of archaeal viruses has been – and still is – a most exciting area of research with the discovery of unique viruses (another confirmation of the three domains concept). The study of these viruses led recently to the first identification of A form DNA in vivo and of a new organization of lipids (horse shoe) in viral membrane by the group of David Prangishvili. The study of virus/host interaction will be an important topic in the next decade as well as the identification and study of new viruses in a more diverse collection of Archaea.

The discovery of Archaea in all possible environments by molecular techniques has been a major advance in the fields during the last ten years. The study of Archaea associated with humans (methanogens and possibly Thaumarchaeota) and their interaction with the immune system, role in the microbiome, possible involvement in metabolic diseases, and so on, should be a priority area of research.

Deciphering the topology of the tree of life and determining the nature of LUCA will remain important areas of research. In particular, it should be possible to reconstitute in more and more details the nature of the last common ancestor of Archaea and Eukarya by summing all eukaryotic features presently distributed between diverse archaeal lineages.

The origin of archaeal viruses, the reasons for their extraordinary diversity (compared to bacterial viruses), and their connection with eukaryotic viruses (especially the so-called giant viruses) will remain big question marks worth of more studies and hypotheses.

What would you like the public (and general microbiological audience) to appreciate about Archaea?

Most people still ignore the existence of Archaea! Many biologists still confuse them with “old” or “strange” bacteria. Many virologists still called archaeal viruses “bacteriophages” because of the eukaryote/prokaryote paradigm. Overall, the general public and many biologists still consider bacteria (and archaea by the way) as primitive organisms. The three domains concept teach us that both Archaea and Bacteria are not primitive but the products of a long evolutionary period after the divergence of their lineage from LUCA, explaining the complexity of their molecular biology. I would like the public and general microbiological audience to appreciate both the uniqueness of archaea and their evolutionary and ecological importance. Studying Archaea is simply essential to understand the history of life on our planet.


Are there any particular papers that you feel are absolute must reads for those that aren’t necessarily familiar with the field (and briefly, why)?

This is a difficult task, as primary papers are quite specialized and there are so many good reviews. Among the latter, I would choose:

Wagner A et al, Mechanisms of gene flow in archaea, Nat Rev Microbiol., 15(8):492-501 (2017)

Prangishvili D.,The wonderful world of archaeal viruses, Annu Rev Microbiol., 67:565-85 (2004)

Sapp J. and Fox G., The singular quest for a universal tree of life, Microbiol Mol Biol Rev., 77(4):541-50 (2013)

For another viewpoint on the position of Asgards in the tree of life and the origin of eukaryotes, I'd suggest:

da Cunha, V. et al., Lokiarchaea are close relatives of Euryarchaeota, not bridging the gap between prokaryotes and eukaryotes, PLoS Genet. 13(6):e1006810 (2017)

I also cannot avoid recommending reading my book, “Microbes from Hell” (Chicago University Press, 2016), where I describe the discovery of Archaea by Carl Woese and the discovery of hyperthermophiles by Karl Stetter and Wolfram Zillig.

Go to the profile of Claudio Nunes-Alves

Claudio Nunes-Alves

Senior Editor, Nature Microbiology

I'm a senior editor at Nature Microbiology, interested in all things bacteria, virus, archaea, fungi and parasites (but I mostly handled articles focusing on bacterial physiology, evolution, parasites and archaea). Before joining Nature, I studied biochemistry at the University of Porto, Portugal, as an undergrad; and was a grad student and post-doc in the labs of Margarida Correia-Neves (ICVS, Braga, Portugal), Sam Behar (Brigham and Women's Hospital and Harvard Medical School, Boston, MA, and then at UMass Medical School, Worcester, MA) and Christophe Benoist (at Harvard Medical School, Boston, MA), where I studied multiple aspects of immunity to tuberculosis.

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