The Gene: An Intimate History - Siddhartha Mukherjee Page 0,48

in close enough, you might see the dots as individual, discrete. But what we observed and experienced in the natural world from afar was an aggregation of dots: pixels merging to form a seamless picture.

The second reconciliation—between genetics and evolution—required more than mathematical modeling; it hinged on experimental data. Darwin had reasoned that evolution works via natural selection—but for natural selection to work, there had to be something natural to select. A population of organisms in the wild must have enough natural variation such that winners and losers can be picked. A flock of finches on an island, for instance, needs to possess enough intrinsic diversity in beak sizes such that a season of drought might be able to select birds with the toughest or longest beaks. Take that diversity away—force all finches to have the same beak—and selection comes up empty-handed. All the birds go extinct in a fell swoop. Evolution grinds to a halt.

But what is the engine that generates natural variation in the wild? Hugo de Vries had proposed that mutations were responsible for variation: changes in genes created changes in forms that could be selected by natural forces. But de Vries’s conjecture predated the molecular definition of the gene. Was there experimental proof that identifiable mutations in real genes were responsible for variation? Were mutations sudden and spontaneous, or were abundant natural genetic variations already present in wild populations? And what happened to genes upon natural selection?

In the 1930s, Theodosius Dobzhansky, a Ukrainian biologist who had emigrated to the United States, set out to describe the extent of genetic variation in wild populations. Dobzhansky had trained with Thomas Morgan in the Fly Room at Columbia. But to describe genes in the wild, he knew that he would have to go wild himself. Armed with nets, fly cages, and rotting fruit, he began to collect wild flies, first near the laboratory at Caltech, then on Mount San Jacinto and along the Sierra Nevada in California, and then in forests and mountains all over the United States. His colleagues, confined to their lab benches, thought that he had gone fully mad. He might as well have left for the Galápagos.

The decision to hunt for variation in wild flies proved critical. In a wild fly species named Drosophila pseudoobscura, for instance, Dobzhansky found multiple gene variants that influenced complex traits, such as life span, eye structure, bristle morphology, and wing size. The most striking examples of variation involved flies collected from the same region that possessed two radically different configurations of the same genes. Dobzhansky called these genetic variants “races.” Using Morgan’s technique of mapping genes by virtue of their placement along a chromosome, Dobzhansky made a map of three genes—A, B, and C. In some flies, the three genes were strung along the fifth chromosome in one configuration: A-B-C. In other flies, Dobzhansky found that configuration had been fully inverted to C-B-A. The distinction between the two “races” of flies by virtue of a single chromosomal inversion was the most dramatic example of genetic variation that any geneticist had ever seen in a natural population.

But there was more. In September 1943, Dobzhansky launched an attempt to demonstrate variation, selection, and evolution in a single experiment—to re-create the Galápagos in a carton. He inoculated two sealed, aerated cartons with a mixture of two fly strains—ABC and CBA—in a one-to-one ratio. One carton was exposed to a cold temperature. The other, inoculated with the same mixture of strains, was left at room temperature. The flies were fed, cleaned, and watered in that enclosed space for generation upon generation. The populations grew and fell. New larvae were born, matured into flies, and died in that carton. Lineages and families—kingdoms of flies—were established and extinguished. When Dobzhansky harvested the two cages after four months, he found that the populations had changed dramatically. In the “cold carton,” the ABC strain had nearly doubled, while the CBA had dwindled. In the carton kept at room temperature, the two strains had acquired the opposite ratio.

He had captured all the critical ingredients of evolution. Starting with a population with natural variation in gene configurations, he had added a force of natural selection: temperature. The “fittest” organisms—those best adapted to low or high temperatures—had survived. As new flies had been born, selected, and bred, the gene frequencies had changed, resulting in populations with new genetic compositions.

To explain the intersection of genetics, natural selection, and evolution in formal terms, Dobzhansky resurrected two important words—genotype and phenotype. A genotype