[p2p-research] First-ever Blueprint of A Minimal Cell Is More Complex Than Expected

[Ryan]

  Sent to you by Ryan via Google Reader: First-ever Blueprint of A
Minimal Cell Is More Complex Than Expected via CellNEWS by ZenMaster on
11/28/09
EMBL and CRG scientists reveal what a self-sufficient cell cannot do
without
Saturday, 28 November 2009

What are the bare essentials of life, the indispensable ingredients
required to produce a cell that can survive on its own? Can we describe
the molecular anatomy of a cell, and understand how an entire organism
functions as a system? These are just some of the questions that
scientists in a partnership between the European Molecular Biology
Laboratory (EMBL) in Heidelberg, Germany, and the Centre de Regulacio
Genòmica (CRG) in Barcelona, Spain, set out to address. In three papers
published back-to-back today in Science, they provide the first
comprehensive picture of a minimal cell, based on an extensive
quantitative study of the biology of the bacterium that causes atypical
pneumonia, Mycoplasma pneumoniae. The study uncovers fascinating
novelties relevant to bacterial biology and shows that even the
simplest of cells is more complex than expected.

Mycoplasma pneumoniae is a small, single-cell bacterium that causes
atypical pneumonia in humans. It is also one of the smallest
prokaryotes – organisms whose cells have no nucleus – that do not
depend on a host's cellular machinery to reproduce. This is why the six
research groups, which set out to characterize a minimal cell in a
project headed by scientists Peer Bork, Anne-Claude Gavin and Luis
Serrano, chose M. pneumoniae as a model: it is complex enough to
survive on its own, but small and, theoretically, simple enough to
represent a minimal cell – and to enable a global analysis.

A network of research groups at EMBL's Structural and Computational
Biology Unit and CRG's EMBL-CRG Systems Biology Partnership Unit
approached the bacterium at three different levels. One team of
scientists described M. pneumoniae's transcriptome, identifying all the
RNA molecules, or transcripts, produced from its DNA, under various
environmental conditions. Another defined all the metabolic reactions
that occurred in it, collectively known as its metabolome, under the
same conditions. A third team identified every multi-protein complex
the bacterium produced, thus characterising its proteome organisation.

"At all three levels, we found M. pneumoniae was more complex than we
expected", says Luis Serrano, co-initiator of the project at EMBL and
now head of the Systems Biology Department at CRG.

When studying both its proteome and its metabolome, the scientists
found many molecules were multifunctional, with metabolic enzymes
catalyzing multiple reactions, and other proteins each taking part in
more than one protein complex. They also found that M. pneumoniae
couples biological processes in space and time, with the pieces of
cellular machinery involved in two consecutive steps in a biological
process often being assembled together.

This image represents the integration of genomic, metabolic, proteomic,
structural and cellular information about Mycoplasma pneumoniae in this
project: one layer of an Electron Tomography scan of a bottle-shaped M.
pneumoniae cell (grey) is overlaid with a schematic representation of
this bacterium's metabolism, comprising 189 enzymatic reactions, where
blue indicates interactions between proteins encoded in genes from the
same functional unit. Apart from these expected interactions, the
scientists found that, surprisingly, many proteins are multifunctional.
For instance, there were various unexpected physical interactions
(yellow lines) between proteins and the subunits that form the
ribosome, which is depicted as an Electron microscopy image (yellow).
Credit: Takuji Yamada /EMBL.
Remarkably, the regulation of this bacterium's transcriptome is much
more similar to that of eukaryotes – organisms whose cells have a
nucleus – than previously thought. As in eukaryotes, a large proportion
of the transcripts produced from M. pneumoniae's DNA are not translated
into proteins. And although its genes are arranged in groups as is
typical of bacteria, M. pneumoniae doesn't always transcribe all the
genes in a group together, but can selectively express or repress
individual genes within each group.

Unlike that of other, larger, bacteria, M. pneumoniae's metabolism does
not appear to be geared towards multiplying as quickly as possible,
perhaps because of its pathogenic lifestyle. Another surprise was the
fact that, although it has a very small genome, this bacterium is
incredibly flexible and readily adjusts its metabolism to drastic
changes in environmental conditions. This adaptability and its
underlying regulatory mechanisms mean M. pneumoniae has the potential
to evolve quickly, and all the above are features it also shares with
other, more evolved organisms.

"The key lies in these shared features", explains Anne-Claude Gavin, an
EMBL group leader who headed the study of the bacterium's proteome:

"Those are the things that not even the simplest organism can do
without and that have remained untouched by millions of years of
evolution – the bare essentials of life".

This study required a wide range of expertise, to understand M.
pneumoniae's molecular organisation at such different scales and
integrate all the resulting information into a comprehensive picture of
how the whole organism functions as a system – an approach called
systems biology.

"Within EMBL's Structural and Computational Biology Unit we have a
unique combination of methods, and we pooled them all together for this
project", says Peer Bork, joint head of the unit, co-initiator of the
project, and responsible for the computational analysis.

"In partnership with the CRG group we thus could build a complete
overall picture based on detailed studies at very different levels."

Bork was recently awarded the Royal Society and Académie des Sciences
Microsoft Award for the advancement of science using computational
methods. Serrano was recently awarded a European Research Council
Senior grant.

References:
Proteome Organization in a Genome-Reduced Bacterium.
Sebastian Kühner, Vera van Noort, Matthew J. Betts, Alejandra
Leo-Macias, Claire Batisse, Michaela Rode, Takuji Yamada, Tobias Maier,
Samuel Bader, Pedro Beltran-Alvarez, Daniel Castaño-Diez, Wei-Hua Chen,
Damien Devos, Marc Güell, Tomas Norambuena, Ines Racke, Vladimir Rybin,
Alexander Schmidt, Eva Yus, Ruedi Aebersold, Richard Herrmann, Bettina
Böttcher, Achilleas S. Frangakis, Robert B. Russell, Luis Serrano, Peer
Bork, and Anne-Claude Gavin
Science 27 November 2009: 1235-1240, DOI: 10.1126/science.1176343

Transcriptome Complexity in a Genome-Reduced Bacterium.
Marc Güell, Vera van Noort, Eva Yus, Wei-Hua Chen, Justine Leigh-Bell,
Konstantinos Michalodimitrakis, Takuji Yamada, Manimozhiyan Arumugam,
Tobias Doerks, Sebastian Kühner, Michaela Rode, Mikita Suyama, Sabine
Schmidt, Anne-Claude Gavin, Peer Bork, and Luis Serrano
Science 27 November 2009: 1268-1271, DOI: 10.1126/science.1176951

Impact of Genome Reduction on Bacterial Metabolism and Its Regulation.
Eva Yus, Tobias Maier, Konstantinos Michalodimitrakis, Vera van Noort,
Takuji Yamada, Wei-Hua Chen, Judith A. H. Wodke, Marc Güell, Sira
Martínez, Ronan Bourgeois, Sebastian Kühner, Emanuele Raineri, Ivica
Letunic, Olga V. Kalinina, Michaela Rode, Richard Herrmann, Ricardo
Gutiérrez-Gallego, Robert B. Russell, Anne-Claude Gavin, Peer Bork, and
Luis Serrano
Science 27 November 2009: 1263-1268, DOI: 10.1126/science.1177263
.........


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