What Tells a Growing Embryo Where the Head Goes? A Row of Genes in Order

These genes do not build structures themselves. Each one produces a protein that switches other genes on and off, and the combination active in a given band of an embryo tells the cells there which part of the body they belong to. Cells in one band are instructed to make a thoracic segment, those in the next an abdominal one. The instruction is positional rather than structural, so the genes specify what should be built at a location and leave the building to hundreds of other genes downstream.

The arrangement on the chromosome is the remarkable part:

• •The genes sit in a cluster, one after another
• •Their order along the chromosome matches head to tail order
• •The first in the cluster acts nearest the head
• •The last acts nearest the tail
• •They are also switched on in that same sequence in time
• •The correspondence holds in insects and in vertebrates alike

The genes were discovered through mutations producing results that are almost comic in their specificity. A fly with one such mutation grows a second pair of wings where the small balancing organs should be, because a segment has been instructed to become a copy of the one in front of it. Another grows legs where its antennae should be, fully formed and in the right place for antennae. What the mutations do is not damage a structure but misdirect an identity, which is why the substituted part is perfectly made and merely in the wrong place.

The route to the finding ran through fruit fly genetics over most of a century. Odd mutants turning one body part into another were collected and named from the early 1900s, long before anybody could say what a gene was made of, and the collection was maintained for decades because the flies were interesting rather than because anyone knew what they meant. Edward Lewis spent years working out that the responsible mutations lay in a cluster and that their positions corresponded to the body regions affected. The molecular confirmation came in the 1980s, and Lewis shared a Nobel Prize for the work in 1995.

The same genes, recognisable by sequence, are present in flies, mice, fish and humans, which was one of the most consequential findings in twentieth century biology. Mouse versions inserted into flies work, activating fly genes correctly, which means the system predates the split between those lineages by an enormous margin. That shifted how evolution of body form is understood, since large changes in shape need not require new genes and can come from changing where and when these existing ones are active. The loss of limbs in snakes and the number of neck vertebrae in a giraffe are both discussed in those terms.

A cluster of genes assigns identity to bands of an embryo, telling cells which body part to become and leaving the construction to others. They lie on the chromosome in the same order as the parts they specify and switch on in that sequence. Mutations produce perfectly formed legs where antennae belong, and the system is shared across flies, mice and humans.