Multicellular Logic Circuits, Part II: Cells

In my post “Multicellular Logic Circuits, Part I: Evolution,” I discussed evolution and genetic algorithms; I want to continue that discussion here.

There are two salient facts of biology that are completely inescapable. The first is that all organisms are shaped by the process of evolution. The second is that all organisms are constructed from cells.

Furthermore, all complex multicellular organisms begin life as a single cell, and undergo a process of development through cell division to mature into an adult. And no matter how different any two organisms may be on the gross macroscopic level that we are used to, inside their cells the chemical processes of life are fundamentally very similar.

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Thus it is no accident that the titles of the two leading textbooks in molecular biology are The Molecular Biology of the Gene by Watson, et. al. and The Molecular Biology of the Cell by Alberts et. al. [These are both great books. This link to the first chapter of MBOC is an excellent entry point into modern biology. And if you are serious about learning biology, I also strongly recommend the companion Molecular Biology of the Cell: A Problems Approach, by Wilson and Hunt, which will force you to think more actively about the material.]

It therefore seems reasonable that if we want to construct artificial systems that achieve the performance of natural ones, we should consider artificially evolving a system constructed from cells.

Although there are typically many different cell types in a mature multi-cellular organism, all the different cells of the organism, with the exception of sperm and egg cells, share an identical genetic specification in their DNA. The different behavior of cells with identical genetic specifications is the result of the cells having different histories and being subjected to different environments.

More specifically, the behavior of a biological cell is controlled by complex genetic regulatory mechanisms that determine which genes are transcribed into messenger RNA and then translated into proteins. One very important regulatory mechanism is provided by the proteins called “transcription factors” that bind to DNA regulatory regions upstream of the protein coding regions of genes, and participate in the promotion or inhibition of the transcription of DNA into RNA. The different histories of two cells might lead to one having a large concentration of a particular transcription factor, and the other having a low concentration, and thus the two cells would express different genes, even though they had identical DNA.

Another important mechanism that controls the differential development of different types of cells in a multi-cellular organism is the biochemical signaling sent between cells. Signals such as hormones have the effect of directing a cell down a particular developmental pathway.

In general, the transcription factors, hormones, and multitude of other control mechanisms used in biological cells are organized into a network which can be represented as a “circuit” where the state of the system is characterized by the concentrations of the different biochemical ingredients. In fact, biologists are now using wiring diagrams to help summarize biological circuits; see for example, the “Biotapestry editor” developed by Eric Davidson’s lab at Caltech.

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[I strongly recommend Davidson’s recent book The Regulatory Genome: Gene Regulatory Networks in Development and Evolution for an exciting introduction to the burgeoning “evo-devo” field; if you don’t have any background in biology, you may prefer The Coiled Spring, by Ethan Bier for a somewhat more popular account.]

Turning to the problem of designing artifical systems, a natural question is what theoretical advantages exist, from the point of view of designing with evolution, to using an identical genetic specification for all the cells in a multi-cellular organism.

One potential advantage is that relatively small changes to the genetic specification of the organism can concurrently alter the behavior of many different kinds of cells at many different times during the development of the organism. Therefore, if there is the possibility of an advantageous change to the circuitry controlling a cell, then it can be found once and used many times instead of needing to find the same advantageous mutation repeatedly for each of the cells in the organism.

Another related potential advantage is that a highly complicated organism can be specified in a relatively compact way. If each of the trillions of cells in a complex organism like a human had to be separately specified, then the overall amount of information required to describe the human genome would be multiplied more than a trillion-fold. Clearly, it is much more efficient to re-use the identical circuitry in many different types of cells.

In other words, biology uses a strategy of specifying a complex multi-cellular organism by just specifying a single cell–all the other cells in the mature organism are grown organically out of the developmental process. This seems like a strategy worth imitating.

On the other hand, the constraint that each cell in an organism should share an identical genetic specification clearly causes complications from the point of view of design. For example, it is important that genes that are designed to function in one type of cell at one point in development not cause problems for different type of cell at a different point in development. Clearly, good design of the control logic that turns genes on and off is essential to the proper functioning of a multi-cellular organism.

In the next post in this series, I will turn to the construction of a concrete model for multi-cellular circuits that tries to capture, as simply as possible, the essence of what is happening in biology. 

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2 Responses to “Multicellular Logic Circuits, Part II: Cells”

  1. son1 Says:

    In other words, biology uses a strategy of specifying a complex multi-cellular organism by just specifying a single cell–all the other cells in the mature organism are grown organically out of the developmental process. This seems like a strategy worth imitating.

    On the other hand, the constraint that each cell in an organism should share an identical genetic specification clearly causes complications from the point of view of design. For example, it is important that genes that are designed to function in one type of cell at one point in development not cause problems for different type of cell at a different point in development. Clearly, good design of the control logic that turns genes on and off is essential to the proper functioning of a multi-cellular organism.

    I know that there are some people who harbor the (outlandish) idea that the genome is more plastic, during development, than we might otherwise expect.

    More concrete and less-outlandish are ideas about genomic structure that affect gene transcription and effect a particular kind of regulation. Maybe you call it epigenetics, although I’ve heard Davidson complain about people applying that term indiscriminately to things that aren’t properly ‘epi-‘.

    But at any rate, it’s certainly the case that not all of the genome’s ‘circuitry’ is expressed in terms of regulatory connections between transcription factors and their attracting sequences, the cis- and trans- of Jacob and Monod. Especially during development, you need to pay attention to thinks like chromatin structure and chromatin marks — there is a whole zoo of ‘marks’ which can be laid down on the DNA itself, at least some of which probably have causal effects on transcription.

    The DNA itself has a state, and that state essentially dictates which portions of the ‘circuitry’ is available for use at any one time. I suppose you could roll DNA state into your notion of cellular state, and maybe also DNA plasticity with a notion of rewrite rules or something… but then it seems like things become a lot more complicated, and aren’t easily expressed in the simple graphical terms that tools like Biotapestry like to output.

    On the other hand, I am not a biologist, so…

  2. Cells Weekly #45 « Migrations Says:

    […] Multicellular Logic Circuits, Part II: Cells – A relatively new science blog brings us an educational review of eukaryotic gene regulatory networks. Go check it out if you need a crash course in signal transduction. At Nerd Wisdom. […]

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