outlookoutlook Life’s demons: information and order in biology What subcellular machines gather and process the information necessary to sustain life? Philippe M. Binder & Antoine Danchin n his seventeenth-century classic, literature, in which it is frequently used to …biological Demons use Novum Organum, Francis Bacon wrote, refer to stored data, or to some mysterious information from within the I“we cannot command nature except quality carried by matter or energy. Instead, cell to counteract the inexorable by obeying her” (Bacon, 2010). Although we define information as a quantity that our knowledge of living systems is much is transferred—without necessarily being effects of ageing, as well as improved since Bacon’s time, we are still conserved—during a measurement pro- permitting the creation of a far from understanding—or commanding— cess, as correlations are created between young progeny from old cells all the complex mechanisms of life. To take the states of the measured and measuring full advantage of living organisms for the systems. Such a view of information has interacting complex networks of genes and benefit of mankind, we will need to under- increasingly been considered by physicists proteins corresponding to functional mod- stand those mechanisms to the furthest pos- as an extension of and alternative to the ules (Oltvai & Barabási, 2002); or included sible extent. To do so will require that the more-traditional concept of entropy (Caves, the concept of a set of digital-like con- concept of information and the theories of 1993; Landauer, 1991; Zurek, 1989). In nected modules that represent biochemical information science take a more-prominent support of Landauer’s idea, Toyabe and col- functions, within which information—in the role in the understanding of living systems. leagues recently claimed to have converted informal sense—flows between modules Two decades ago, Rolf Landauer information directly into energy (Toyabe (Nurse, 2008). These concepts, although (1991) argued that “information is physi- et al, 2010). This definition contrasts with, useful, are overly mechanistic and fall short cal” and ought to have a role in the scien- for example, the measure of how many of capturing life’s unbounded spontaneity tific analysis of reality comparable to that bits can be carried by a memory device and adaptability. of matter, energy, space and time. This such as DNA—also called information would also help to bridge the gap between capacity—and with the most-compressed e therefore summon Maxwell’s biology and mathematics and physics. description of a specific arrangement of Demon (MxD; Leff & Rex, Although it can be argued that we are liv- bits, such as a genome, which is also called W2002) and its distant relative ing in the ‘golden age’ of biology, both algorithmic information. the ratchet (Serreli et al, 2007), and apply because of the great challenges posed by these to bio logy. The original Demon medicine and the environment and the …we feel that information was the brain-child of Scottish physicist significant advances that have been made— as an essential aspect of life James Clerk Maxwell. In 1867, in a let- especially in genetics and molecular and ter to Tait, Maxwell proposed a thought cell biology—we feel that information as an has been neglected, or at least experiment to “show that the Second Law essential aspect of life has been neglected, misunderstood of Thermodynamics has only a statisti- or at least misunderstood. cal certainty” (Leff & Rex, 2002). Maxwell Theoretical biology has not yet em - conceived of a device to identify and sepa- ere we propose to look at living braced such a notion of information, rate fast and slow particles in order to set organisms as information gather- although the field has advanced beyond up a temperature or pressure gradient, thus Hing and utilizing systems (IGUSs; the idea of open, non-equilibrium systems producing an asymmetrical gas configura- Gell-Mann, 1994) that process information that sustain structures and functions as mat- tion to yield useful work with an apparent about their environment to make decisions ter and energy flow through them. Recent decrease in the entropy of the Universe. about their actions. To do so, we require a attempts to describe life have used large sets Although imaginary, MxD has become definition of ‘information’ that transcends of coupled, non-linear differential equa- a crucial tool for physicists who seek to the informal use of the term in the biology tions (Tomita et al, 1999); considered large, understand information and its processing. ©2011 EUROPEAN MOLECULAR BIOLOGY ORGANIZATION EMBO reports VOL 12 | NO 6 | 2011 495 science & society outlook so complete bacterial genomes (Lagesen et al, 2010) that have been sequenced so far, let alone all the other genomes of eukaryotic organisms. Fortunately, analysis of gene persist- ence—the tendency of genes to be present in a quorum of genomes—has allowed us to identify the paleome, a common set of genes that code for the essential functions that maintain life (Danchin et al, 2007). Most of these functions are easily accounted for as they are involved in the construction, reproduction and maintenance of cellular structures and the replication of genomes. Yet, some functions, thought to be involved in maintenance or degradation, are found to use energy in a way that is not obviously Fig 1 | A schematic of Maxwell’s Demon operating within a cell. MxD molecule (with a trident), coded linked to their role. Hence, the unexpected by DNA (helix) along with other proteins, distinguishes functional and damaged proteins. The latter are use of apparent ly wasted energy can be contained or discarded. MxD, Maxwell’s Demon. seen as an evidential ‘smoking gun’ for MxDs of the sort we describe. One example of such energy ‘waste’ Our demon is somewhat different: it is variety of reasons: repeated transitions might be a kinetic proofreading mechanism an existing biological mechanism that uses between metabolic states, hot or cold during translation (Gueron, 1978; Hopfield, information from its surroundings to create a temperatures, reactive oxygen species, 1974), which involves information transfer, locally ordered environment, while obeying glycation, or other aggressive chemical memory and reset. Reading a codon of the the second law of thermodynamics. Thus, reactions. Perhaps as importantly, some genetic message requires interaction with a by definition, our MxD is an IGUS. As infor- amino-acid residues undergo spontaneous cognate-adaptor molecule—a transfer RNA mation transfer implies a change in the state isomerization that causes functional decay loaded with the amino acid corresponding of the MxD device itself, it turns out that in in a way that is conceptually reminiscent to the codon—on the ribosome, a nano- order to operate again, the MxD first has to of the half-life of radioactive isotopes. In machine that translates messenger RNA be reset to its original state; this step carries order for life to go on, these aged and dys- codon after codon, in a ratchet-like man- an entropy cost, usually with an associated functional metabolites must be identified ner. There is enough energy in the chemi- energy input, a fact that has an important and either discarded, degraded or repaired cal bond that links the amino acid to the role, as discussed here. during normal cell operation, and even transfer RNA to permit polymerization into more so during cell reproduction, in which a protein. Yet, a further step is required, …the unexpected use of the segregation of new and old molecules with an apparently useless consumption of apparently wasted energy can guaran tees the survival of new daughter energy. The loaded transfer RNA is bound be seen as an evidential ‘smoking cells. Enter Maxwell’s Demon: a mecha- to a factor (EFTu) that tests the accuracy of nism that differentiates functional and dys- the decoding process; there is competi- gun’ for Maxwell’s Demons of the functional proteins, perhaps by measuring tion between transfer RNAs at the entry sort we describe their shapes and vibration spectra (Schwartz site in the ribosome, and incorrect transfer & Schramm, 2009), and segregates normal RNAs are more common than correct ones. In a biological context, we postulate proteins from defect ive ones using exist- When the correct one is bound, free EFTu the existence of MxDs in every cell, but ing cellular structures, or by generating is released at the expense of a molecule of with a different role than their counterparts new ones (Fig 1). energy-rich GTP. Energy consumption is from physics: biological Demons use infor- only used at this stage to achieve a more- mation from within the cell to counteract ow can we identify the entities, ‘ordered’ state of genetic-code use during the inexorable effects of ageing, as well as proteins or complexes that play translation. At the least, this is the work of permitting the creation of young pro geny Hthe role of MxDs? If they exist, an IGUS, and at best it could be the earli- from old cells. This is based on a view of they must be in genomes. They must also be est MxD (unknowingly) discovered in a cells as machines that make copies of them- essential for life to perpetuate in a sustain- cellular process. selves through organized coupling of the able way. Hence, the corresponding func- processes of replication—copying the DNA tions should be encoded in all genomes. If ow then might other biological ‘program’—and reproduction: a slightly it was possible, an easy way to find them MxDs manifest themselves? All imperfect duplication of the metabolic would be to search for genes that are com- Hcells, including bacteria, age and machinery and cellular structures. mon to all genomes. Unfortunately, because eventually deteriorate in unfavourable con- The proteins that implement metabo- life conserves functions but not structures, ditions.