The mechanism that gives shape to life

October 17, 2011

(Credit: Pascal Coderay/EPFL)

Researchers at EPFL (Ecole Polytechnique Fédérale de Lausanne) and the University of Geneva (Unige) have solved the mystery of how genes determines the shape that many animals take.

During the development of an embryo, everything happens at a specific moment. In about 48 hours, it will grow from the top to the bottom, one slice at a time — scientists call this the embryo’s segmentation. “We’re made up of thirty-odd horizontal slices,” explains Denis Duboule, a professor at EPFL and Unige. “These slices correspond more or less to the number of vertebrae we have.”

Every hour and a half, a new segment is built. The genes corresponding to the cervical vertebrae, the thoracic vertebrae, the lumbar vertebrae and the tailbone become activated at exactly the right moment one after another.

DNA acts like a mechanical clock

Very specific genes, known as “Hox,” responsible for the formation of limbs and the spinal column, are involved in this process. “Hox genes are situated one exactly after the other on the DNA strand, in four groups. First the neck, then the thorax, then the lumbar, and so on,” explains Duboule.

The process is astonishingly simple. In the embryo’s first moments, the Hox genes are dormant, packaged like a spool of wound yarn on the DNA. When the time is right, the strand begins to unwind. When the embryo begins to form the upper levels, the genes encoding the formation of cervical vertebrae come off the spool and become activated. Then it is the thoracic vertebrae’s turn, and so on down to the tailbone. The DNA strand acts a bit like an old-fashioned computer punchcard, delivering specific instructions as it progressively goes through the machine.

“A new gene comes out of the spool every 90 minutes, which corresponds to the time needed for a new layer of the embryo to be built,” explains Duboule. “It takes two days for the strand to completely unwind; this is the same time that’s needed for all the layers of the embryo to be completed.” This system is the first “mechanical” clock ever discovered in genetics. And it explains why the system is so remarkably precise.

Player-piano music

The structure of all  animals — the distribution of their vertebrae, limbs and other appendices along their bodies — is programmed like a sheet of player-piano music by the sequence of Hox genes along the DNA strand.

The sinuous body of the snake is a perfect illustration. A few years ago, Duboule discovered in these animals a defect in the Hox gene that normally stops the vertebrae-making process. “Now we know what’s happening. The process doesn’t stop, and the snake embryo just keeps on making vertebrae, all identical, until the process just runs out of steam.”

The Hox clock is a demonstration of the extraordinary complexity of evolution. One notable property of the mechanism is its extreme stability, explains Duboule. “Circadian or menstrual clocks involve complex chemistry. They can thus adapt to changing contexts, but in a general sense are fairly imprecise. The mechanism that we have discovered must be infinitely more stable and precise. Even the smallest change would end up leading to the emergence of a new species.”

Ref.: D. Noordermeer, M. Leleu, E. Splinter, J. Rougemont, W. De Laat, D. Duboule. The Dynamic Architecture of Hox Gene Clusters. Science, 2011; 334 (6053): 222 DOI: 10.1126/science.1207194