Physics of Life (2022) / Chapter Skim
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2 How Do Living Systems Represent and Process Information?
2 How Do Living Systems Represent and Process Information?
Pages 88-118
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From page 88... ...
Understanding the physics of living systems requires us to understand how information flows across many scales, from single molecules to groups of organisms. From the theoretical side, these explorations often have reinforced the deep connections between statistical physics and information theory, and on the experimental side we have seen the development of extraordinary new measurement techniques.
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From page 89... ...
As described previously, these results emerged from an interplay among physics, chemistry, and biology, and these basic facts about DNA and the encoding of genetic information are now taught to high school students. But the search for physical principles of genetic information transmission did not stop with the discovery of the double helix.
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From page 90... ...
molecules to amino acids; and in the binding of tRNAs to mRNA during the translation of the mRNA sequence into the amino acid sequence of proteins. In each case living cells achieve a sorting of molecular components that is vastly more accurate than would be expected from energy differences alone.
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From page 91... ...
Similarly, in order to lower the error probabilities in processing information encoded in DNA, the cell expends extra energy in the processes of DNA replication, transcription, tRNA charging, and translation. Although the details vary, all of these processes involve steps that dissipate energy, sometimes in apparently wasteful ways, but these futile steps serve to increase precision.
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From page 92... ...
living cells, the codebook for the genetic code is embodied in b, Power spectrum acquired the tRNA molecules for a stiffly trapped bead with external optics under air (red) or helium (blue)
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From page 93... ...
Regulatory Sequences Beyond the DNA sequences that encode the amino acid sequences of proteins, there are sequences that carry information about how the synthesis of proteins is regulated. This reading out of genetically encoded information is referred to as "expression" of the corresponding genes.
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From page 94... ...
This is exactly what is expected from the equilibrium statistical mechanics models -- these two numbers are the free energy Model Fit Next we us protein-DN scription. B signs to ea interest, su or the rate multiple p specific m the values dent predi Such m way if we probability quantity of FIGURE 2.2 How much information, in bits, do DNA sequences provide about gene expression?
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From page 95... ...
It now is possible to measure directly the looping of DNA in response to transcription factor binding, although it remains challenging to connect these single molecule experiments to the macroscopic behavior of gene expression, quantitatively. The relatively simple picture of these processes in bacteria, where a small number of transcription factors regulate the expression of nearby genes, stands in contrast to what has been learned about the control of gene expression in higher organisms.
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From page 96... ...
Our immune system also carries a memory, but humans do not pass this information on to their offspring. Theorists in the biological physics community have tried to understand how the different dynamics of environmental challenges drive the emergence of these different strategies in different classes of organisms.
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From page 97... ...
In each of these cases and more, it is reasonable to expect progress in the coming decade both from the introduction of new experimental methods and from the formulation of sharper theoretical questions about how these systems function. INFORMATION IN MOLECULAR CONCENTRATIONS Throughout the living world, information crucial to life's functions is represented or encoded in the concentrations of specific molecules.
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From page 98... ...
The output of the cell is an electrical voltage or current across the membrane, but this current flows through channels whose state is controlled by the concentration of a small signaling molecule, cGMP. In this sense, light intensity is represented internally by the concentration of cGMP, and this concentration in turn is the result of a cascade of molecular events.
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From page 99... ...
Measurement with fluorescent proteins in single cells allowed the first measurements of noise in transcriptional control, separating intrinsic noise in the control mechanism from extrinsic variations in cellular conditions. This led to a flurry of theoretical work, trying both to understand the precise physical origins of this noise and to explore the implications of noise for information transmission.
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From page 100... ...
One approach uses microfluidic methods developed in the biological physics community to manipulate large numbers of single cells, ultimately breaking them open and identifying all of their mRNA molecules using biochemical sequencing methods (Chapter 6)
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From page 101... ...
FIGURE 2.5 There is considerable interest from both the biological physics community and the biology community in understanding information flow through networks that control transcription of genes. Toward this end, methods have been developed for counting individual transcripts (i.e., messenger RNA [mRNA]
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From page 102... ...
Left, an embryo stained with antibodies to the protein Bicoid, a transcription factor that accumulates in the nuclei. Darkness of the stain is proportional to concentration, which is larger at the end of the embryo that will become the head.
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From page 103... ...
Primary morphogens have absolute concentrations that are reproducible from embryo to embryo with ∼8 percent accuracy. This precision occurs despite the fact that relevant molecules are present at low concentrations, as with other transcription factors, and these notions of precision could be formalized in the language of statistical physics and information theory.
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From page 104... ...
For this long distance communication of information, the con tinuously varying currents are converted into discrete electrical pulses, called action potentials or spikes. Spikes can propagate without decaying or changing shape, at an essentially constant speed, until they reach the synapse where one cell connects to another.
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From page 105... ...
There was a long path from quantitative observations on the relatively macroscopic electrical dynamics of single neurons to a precise mathematical and physical description of the underlying molecular events, including the structures of the relevant molecules, the ion channel proteins that are embedded in the cell membrane. Along the way were the very first direct measurements of dynamics in single molecules, the observations of electrical current flow through these channels.
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From page 106... ...
If this is correct, then small patches of membrane will have small numbers of these channel molecules, and since single molecules behave randomly, the resulting current flow will have measurable randomness or noise, and it does. FIGURE 2.7 The macroscopic electrical dynamics of cells results from the underlying dynamics of specific protein molecules -- ion channels -- that are embedded in the cell membrane.
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From page 107... ...
In a different direction, electrical signaling through action potentials, or through smaller amplitude graded changes in voltage, provide concrete examples where we can understand the energy costs of coding and computation in the nervous system. Our understanding of the inherently stochastic molecular dynamics of the channel molecules also means we can characterize the reliability or fidelity of information transmission and processing, and relate these measures of performance to the
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From page 108... ...
Approaching the brain's output, one can once again see the correlation of single spikes and patterns of spikes with particular trajectories of muscle activity. The biological physics community has been keenly interested in the more ab stract properties of the code by which sensory signals and motor commands are represented by sequences of action potentials.
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From page 109... ...
Alternatively, many tasks require organisms to make predictions, and perhaps it this predictive information which is almost always relevant. These ideas have deep connections to many problems in statistical physics and dynamical systems, and have even led to experiments that estimate the amount of information that small populations of neurons carry about the future of their sensory inputs.
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From page 110... ...
Theories of collective behavior make predictions for the structure of measurable correlations, but one can also turn the argument around and ask for the simplest collective states that are consistent with the measured correlations. These ideas are deeply grounded in statistical physics, and have con nections to other examples of emergent behaviors of living systems, as discussed in Chapter 3.
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From page 111... ...
The exploration of information flow in the brain also has led to remarkable experimental methods for monitoring the FIGURE 2.8 The stable states of activity maps to a ring, making a network of neurons that represent orientation or direction of special interest. An example of a ring of neural states exists in the brains of flies.
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From page 112... ...
Bacterial communication could be a byproduct of more basic pro cesses: As bacteria grow and move through a medium, they consume resources, and other bacteria navigate the resulting concentration gradients. But it had been known since 1970 that single celled organisms can communicate more directly, and in parallel with the biological physics community's interest in pattern formation, microbiologists were exploring the molecular basis of this communication and realizing that it is widespread among bacteria.
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From page 113... ...
More modestly, cells make decisions to attach to surfaces and grow communally only when there are enough compatriots in the neighborhood. As with modern work from the biological physics community on flocks and swarms (Chapter 3)
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From page 114... ...
Bassler, 2016, Vibrio cholerae biofilm growth program and architecture revealed by single-cell live imaging, Proceedings of the National Academy of Sciences U.S.A. 112:E5337, Creative Commons License CC BY-NC-ND 4.0.
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From page 115... ...
A single cell contracts its body by ~60 percent within milliseconds in ÿ ÿ ÿ 5+-%&$5%/+-2ÿI6ÿJ=,'&/*
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From page 116... ...
Vocal Communication Our human preoccupation with vocal communication leads to special interest in other animals that use the same modality. Frog calls, bird songs, and the mys terious sounds of whales and dolphins all attract our attention, and the attention of the physics community.
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From page 117... ...
As discussed in Chapters 4 and 7, these models have their roots in statistical physics models for networks of real neurons in the brain, and many people see statistical physics as a natural language Group within which to understand why such systems work so well. Among other features,
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From page 118... ...
Although this effort involved contri butions from many disciplines, there has been special interest from the biological and statistical physics communities. As emphasized in Chapter 3, neural networks are a continuing source of new physics problems, and the language processing systems push these questions into new and unexplored regimes.
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