The Jumping Genes

Finding Mobile DNA in Maize Chromosomes

In the summer of 1944, in an irrigated field beside Bungtown Road at the Cold Spring Harbor Laboratory on Long Island, cytogeneticist Barbara McClintock walked between rows of Zea mays, fastening brown paper bags over emerging corn silks and tassels to control every grain of pollen. Wearing sneakers and khaki trousers, she planted, hand-pollinated, and harvested every ear herself without technicians, tracking the lineage of every kernel through five generations of notebooks.

At the close of World War II, the consensus in genetics rested on the chromosomal map established by Thomas Hunt Morgan's Drosophila group and the "one gene, one enzyme" doctrine of George Beadle and Edward Tatum. In that model, chromosomes were stable, linear strings of beads. Every gene occupied a fixed physical address—its locus—along a chromosome from fertilization to death, changing only when struck by X-rays or mutagens, or when segments exchanged symmetrically during meiotic crossing-over.

McClintock knew maize chromosomes better than anyone alive. In 1931 at Cornell, alongside Harriet Creighton, she had proved that genetic crossing-over corresponded to a physical exchange of chromosome segments under a microscope. Later in the 1930s at the University of Missouri, she discovered the breakage-fusion-bridge cycle: when X-rays snapped off the natural cap (the telomere) of maize chromosome 9, the broken chromatid ends fused together after replication, forming a two-centromere bridge during mitosis that ripped apart at a new site as the daughter nuclei pulled toward opposite poles.

In the winter of 1944–1945 at Cold Spring Harbor, McClintock harvested 450 self-pollinated maize plants grown from parents in which the short arm of chromosome 9 had repeatedly broken and fused. Peeling back the husks, she saw cobs that violated every rule of Mendelian inheritance: individual yellow or white kernels were splattered with hundreds of irregular purple, bronze, and brown spots of varying sizes.

Staining dividing cells with aceto-carmine dye and peering through her Leitz microscope at pachytene chromosomes, McClintock noticed that chromosome 9 was no longer breaking at random points. In plant after plant, the short arm of chromosome 9 was snapping cleanly at one identical site just proximal to the waxy locus. She named this specific genetic locus Dissociation, or $Ds$.

Over six summers of controlled crosses between 1945 and 1950, McClintock followed $Ds$ through thousands of kernels and discovered why the pigment genes flickered off and on. First, $Ds$ was not stationary. Between generations, the $Ds$ element physically detached itself from its home address on chromosome 9, traveled across the chromosome, and inserted itself directly into the middle of the $C$ gene responsible for synthesizing purple anthocyanin pigment in the kernel's aleurone layer. So long as $Ds$ sat wedged inside the $C$ locus, the pigment gene was inactivated and the kernel remained colorless.

Furthermore, $Ds$ could neither break the chromosome nor jump on its own. It moved only when a second, unlinked mobile element—which McClintock discovered and named Activator ($Ac$)—was present in the nucleus. As a colorless kernel carrying a $Ds$-disrupted pigment gene developed, a signal from $Ac$ triggered $Ds$ in certain dividing cells to excise itself cleanly out of the $C$ gene and jump to a new address. The instant $Ds$ jumped out, the repaired $C$ gene switched back on, and that cell—along with all its mitotic descendants—synthesized purple anthocyanin pigment.

Because the size of a purple spot depended on how many cell divisions remained before the seed finished growing, each speckled kernel served as a chronological record: large patches meant $Ds$ had jumped out early in development; tiny pinpricks meant $Ds$ had jumped out during the final divisions; and the dosage of $Ac$ elements regulated the timing of the jumps. The genome was not a static necklace of beads; it contained mobile switches that transposed to regulate gene expression.

In June 1951, McClintock presented her maps at the Cold Spring Harbor Symposium before seventy leading geneticists and phage biologists, including Max Delbrück and Salvador Luria. An audience steeped in linear phage genetics greeted her lecture with stony silence and derision; as McClintock recalled, they thought she had gone mad. After her 1953 paper in Genetics drew only three reprint requests over two years, she stopped publishing on transposition outside internal Carnegie Institution yearbooks. Her exile lasted until 1967–1972, when molecular biologists including James Shapiro, Peter Starlinger, and Sankar Adhya isolated bacterial insertion sequences and transposons jumping across Escherichia coli plasmids. In October 1983, McClintock received the unshared Nobel Prize in Physiology or Medicine, and genome sequencing later confirmed that transposable elements make up 85 percent of the maize genome and nearly 45 percent of the human genome.