Arrival of the Fittest: Solving Evolution's Greatest Puzzle

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Authors: Andreas Wagner
pentachlorophenol.
    Even a modest number of potential fuel molecules gives rise to an astounding number of fuel combinations on which a metabolism may or may not be viable—an astounding number of metabolic phenotypes. To see how many, imagine a list like that shown in figure 6, comprising a hundred or so potential fuels. Then compute whether the known metabolism of your favorite animal, plant, or bacterium is viable on a specific fuel molecule, such as glucose. If it can synthesize all biomass molecules from the carbon in glucose, write a “1” next to glucose, otherwise write a “0.” Then repeat this computation for the next fuel molecule, the next one after that, and so on, until each fuel has either a “0” or a “1” next to it. Every single “1” in this list means that the metabolism can synthesize the complete suite of biomass molecules from that particular fuel.
    The resulting string of a hundred ones and zeroes encapsulates the fuel molecules that a given metabolism can use to sustain life. It is an extremely compact way of summarizing a metabolic phenotype. Metabolic generalists like
E. coli
can survive on dozens of carbon sources, and their phenotype string contains many ones. 35 Metabolic specialists can live on only a few carbon sources, and their phenotypes contain mostly zeroes.
    To count how many such phenotypes exist, the different combinations of a hundred-odd fuels on which an organism
could
be viable, we just need to keep in mind that an organism may (1) or may not (0) be able to live on each fuel—these two and no other possibilities exist. To calculate the total number of possible phenotypes, multiply 2 by itself a hundred times, which yields 2 100 . This number is greater than 10 30 , or a 1 with 30 zeroes added, not quite as large as the number of possible metabolisms, but still a very large number, much larger than, say, the number of stars in our galaxy—approximately 10 11 , or 100 billion.
    I was not kidding when I told you that phenotypes are more complex than the modern synthesis would have you believe.
    This huge number of phenotypes implies an equally huge number of metabolic innovations. Figure 7 shows one example. The figure’s left side displays the fuel phenotype of a metabolism that can survive on some carbon sources, but not on ethanol, hence the zero next to ethanol. New genes—acquired through gene transfer or otherwise—can change the genotype that brings forth this phenotype. If this change allows the mutant to metabolize ethanol, we replace the “0” next to ethanol with a “1.” Because every conceivable metabolic innovation can be written like this, by replacing a “0” with a “1” in a metabolic phenotype, there are about as many possible metabolic innovations as there are phenotypes. 36

     
    Designing a space to house the library of all possible metabolisms would be challenging, in part because its volumes exceed the number of hydrogen atoms in the universe. To allow us to find specific volumes fast, the library would also have to be supremely well organized. It would take me only seconds to find my copy of Darwin’s
Origin
in the small library of my office, but searching for any one book while grazing through the stacks of an average university’s library would be a bad idea. And if somebody had reshelved the
Origin
in the wrong place, it might be lost forever. The problem is much worse in a hyperastronomical library. The universal library might well contain the secret to immortality—or at least the perfect recipe for turkey stuffing—yet the library is so large that we would
never
find it unless we knew where to look.
    FIGURE 7. A metabolic innovation
    An especially simple way to organize the library is to place the most similar texts next to each other. Human librarians do exactly that when they shelve different editions of the same book together. If the metabolic library were organized along these lines, the most similar texts would be

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