April 26, 2004 | David F. Coppedge

Minimal Cell Modeled in Computer

“The basic design rules relating the regulation of cellular function to genomic structure is of broad interest,” begin three Cornell microbiologists writing in PNAS,1 and so they have turned their attention to the smallest theoretical living cell:

A �minimal cell� is a hypothetical cell possessing the minimum functions required for sustained growth and reproduction in a maximally supportive culture environment.  This organism is considered to live in a rich environment with preformed nutrients and relatively constant temperature and pH.

The smallest known independently-living organism, Mycoplasma genitalium, has 580 kilobase pairs of DNA.  Most prior estimates for the smallest theoretical cell arrived at 262 genes or more.  Early investigators started by studying proteins and their functions.  These researchers took a different tack:

We propose a reverse approach.  We ask how we would design a cell to achieve expected functions and, from that design, how we would write the genomic instructions.  This approach follows the typical engineering design approach where desired performance dictates functional design, which is then translated into blueprints.

By evaluating which genes seem to overlap and sorting out genes that have similar functions, this team got the number of genes down to only 12, accomplishing 11 essential functions.  “It is certainly possible that a smaller set of genes might be found,” they say, “but we believe that the set of functions is minimal.”  This theoretical lower limit does not, of course, mean that such an entity could be found or constructed, or if it were, that it could survive and reproduce; their model only “permits growth from preformed nucleotides precursors and has complete nucleotide pathways.”


1Castellanos, Wilson and Shuler, “A modular minimal cell model: Purine and pyrimidine transport and metabolism,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0400962101 (published online before print April 16, 2004).

Their model is little more than a thought experiment.  It imagines “pseudochemical species (or modules) that are aggregates of distinct chemical species that share similar chemistry and metabolic dynamics.”  What they try to do is theorize how simple a cell can be to exist and model it in a computer, not in the real world.  It’s kind of like designing a minimal airplane that could fly around the world without refueling, assuming there is constant temperature and no wind.  When the actual Voyager flew, it involved many engineering and physiological challenges that required even more intelligent design than a simple, heavier airplane.  These authors do not attempt to imagine that their theoretical cell would actually be viable.  It’s only a theoretical organism, a little better fleshed out than the fake computer organisms of Adami and Lenski.
    The authors do not imply that such an entity was a precursor to complex life.  For one thing, their model required pre-existing nucleotides and other ingredients not easy to come by in an organic soup, and assumed unrealistic constant temperature and pH conditions: in essence, they imagined a little garden of Eden for these theoretical cells, not a primitive hostile environment of crashing waves, hot vents, ice ages or meteor impacts.  For another, “This observation reminds us of one of the important challenges for comparative genomics,” they mention in their conclusion: “nonorthologous gene displacements (same function being performed by unrelated or very distantly related nonorthologous proteins).”  While this observation encourages them that “A conserved core of functions with a single, ubiquitous solution certainly exists” (theoretically, in the computer), the fact is that real life has a non-overlapping universal set of 80 genes, and the three kingdoms utilize very different proteins for some similar functions.  This is undoubtedly a reflection of their different habitats and environments.  Are we expected to believe that each of the three kingdoms evolved their own quasi-miraculous solutions to functional requirements independently, on repeated occasions, without brains?
    While the authors consider it “certainly possible” that someone might get the number down below 12 essential genes, they think their set of 11 functions is a rock-bottom minimum.  It won’t help origin-of-life researchers anyway.  Forget getting 12, or 80, or 256 genes: getting just one is out of the question (see our online book).  On Saturday, Dr. Kurt Durston at the Biola ID conference presented his calculations on the information content of a cell.  He said that a minimal cell needs 75,000 bits of information, and showed mathematically that evolutionary selection could not proceed in jumps greater than 90 bits.  Even if it required only one tenth of that, 7500 bits, it’s just not going to happen by chance, even with natural selection’s help.  We agree with the authors: “The basic design rules relating the regulation of cellular function to genomic structure is of broad interest.”

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