Arrival of the Fittest: Solving Evolution's Greatest Puzzle by Andreas Wagner Page B
Book: Arrival of the Fittest: Solving Evolution's Greatest Puzzle by Andreas Wagner
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Authors: Andreas Wagner
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humans first discovered the pastoral lifestyle. They are among the strongest recent signatures that natural selection has left in our genomes. 1
Surprising as it may seem, lactose-induced indigestion is deeply connected with innovation. What connects them is regulation—the tuning of the activity of molecules like the lactase gene. Accounting for much more than intestinal upset, regulation is also complicit in the endlessly varying forms of organisms, the gracefully undulating umbrella of a jellyfish, the lethal torpedo of a shark’s body, the slender stem of a rose, the gargantuan trunk of a redwood tree, the deadly coil of a viper, the light-footed legs of a rabbit, and the soaring wings of a bird. Regulation has come a long way from its murky origins in the first cells, where it balanced the growth of a membrane container with that of an RNA genome. More than three billion years later, regulation is shaping the bodies of every living thing on the planet. And no understanding of innovability would be complete without grasping how new regulation appears.
Although regulation controls the form and function of even the most complex organism, like so much else it is most easily studied in the simplest cells, those of bacteria. This is how two French geneticists, François Jacob and Jacques Monod, won their Nobel Prize. Starting in the 1950s, at a time when the double helix had just been discovered, they showed how primitive bacteria like
E. coli
regulate the expression of the genes that permit them to digest lactose. 2
Gene expression begins with the kind of molecular copying machine that we briefly encountered in Eric Hayden’s experiment in chapter 4. It is a
polymerase
enzyme that makes—the name says it all—a polymer, a stringlike molecule consisting of many smaller building blocks, the four nucleotides that we find in the faithful RNA transcript of a gene. 3 When this polymerase transcribes a gene, it first attaches to the gene’s DNA, slides along this DNA letter by letter, and strings together an RNA molecule whose letter sequence is identical to that of the gene. 4 This is also how bacteria express the gene for
their
variant of lactase, an enzyme called beta-galactosidase. 5 (The name is cumbersome, hence it is often abbreviated as beta-gal.) This enzyme cleaves lactose into the two simpler sugars glucose and galactose, from which other metabolic enzymes can extract energy and carbon.
To regulate the beta-gal gene, cells manipulate its transcription with a
transcriptional regulator
. This protein does mostly one thing: It latches on to short stretches of DNA near a gene. Inside the liquid environment of a cell, multiple kinds of regulators drift this way and that, and whenever any one of them encounters a specific DNA sequence—a DNA “word”—it will bind and stick to it. Different regulators have different keywords—the beta-gal regulator recognizes one that contains the letters GAATTGTGAGC. 6
What enables this recognition is the same folded protein shape that makes enzymes work. Regulator and DNA need to have complementary shapes, a bit like Lego blocks where several small studs on one block fit snugly into indentations on another. The analogy is apt but also limited, because shape is not all that matters. For instance, the two molecules also need to have complementary charges or they may repel each other. And where the standard set of Lego blocks has only a few dozen shapes, molecules have many more, tens of thousands in proteins and even more in DNA, where there are as many shapes as there are possible words. 7
What is more, unlike Lego blocks, many molecules spontaneously change shape, not only when they vibrate like enzymes but also when they bind one another. This shape change is similar to what happens when you insert the right key in a lock: Only then can the lock’s cylinder turn and open a door—although in molecules nothing but heat is doing the turning.
The regulator’s Lego-like
Surprising as it may seem, lactose-induced indigestion is deeply connected with innovation. What connects them is regulation—the tuning of the activity of molecules like the lactase gene. Accounting for much more than intestinal upset, regulation is also complicit in the endlessly varying forms of organisms, the gracefully undulating umbrella of a jellyfish, the lethal torpedo of a shark’s body, the slender stem of a rose, the gargantuan trunk of a redwood tree, the deadly coil of a viper, the light-footed legs of a rabbit, and the soaring wings of a bird. Regulation has come a long way from its murky origins in the first cells, where it balanced the growth of a membrane container with that of an RNA genome. More than three billion years later, regulation is shaping the bodies of every living thing on the planet. And no understanding of innovability would be complete without grasping how new regulation appears.
Although regulation controls the form and function of even the most complex organism, like so much else it is most easily studied in the simplest cells, those of bacteria. This is how two French geneticists, François Jacob and Jacques Monod, won their Nobel Prize. Starting in the 1950s, at a time when the double helix had just been discovered, they showed how primitive bacteria like
E. coli
regulate the expression of the genes that permit them to digest lactose. 2
Gene expression begins with the kind of molecular copying machine that we briefly encountered in Eric Hayden’s experiment in chapter 4. It is a
polymerase
enzyme that makes—the name says it all—a polymer, a stringlike molecule consisting of many smaller building blocks, the four nucleotides that we find in the faithful RNA transcript of a gene. 3 When this polymerase transcribes a gene, it first attaches to the gene’s DNA, slides along this DNA letter by letter, and strings together an RNA molecule whose letter sequence is identical to that of the gene. 4 This is also how bacteria express the gene for
their
variant of lactase, an enzyme called beta-galactosidase. 5 (The name is cumbersome, hence it is often abbreviated as beta-gal.) This enzyme cleaves lactose into the two simpler sugars glucose and galactose, from which other metabolic enzymes can extract energy and carbon.
To regulate the beta-gal gene, cells manipulate its transcription with a
transcriptional regulator
. This protein does mostly one thing: It latches on to short stretches of DNA near a gene. Inside the liquid environment of a cell, multiple kinds of regulators drift this way and that, and whenever any one of them encounters a specific DNA sequence—a DNA “word”—it will bind and stick to it. Different regulators have different keywords—the beta-gal regulator recognizes one that contains the letters GAATTGTGAGC. 6
What enables this recognition is the same folded protein shape that makes enzymes work. Regulator and DNA need to have complementary shapes, a bit like Lego blocks where several small studs on one block fit snugly into indentations on another. The analogy is apt but also limited, because shape is not all that matters. For instance, the two molecules also need to have complementary charges or they may repel each other. And where the standard set of Lego blocks has only a few dozen shapes, molecules have many more, tens of thousands in proteins and even more in DNA, where there are as many shapes as there are possible words. 7
What is more, unlike Lego blocks, many molecules spontaneously change shape, not only when they vibrate like enzymes but also when they bind one another. This shape change is similar to what happens when you insert the right key in a lock: Only then can the lock’s cylinder turn and open a door—although in molecules nothing but heat is doing the turning.
The regulator’s Lego-like
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