Carl Zimmer - Evolution - The Triumph of an Idea

The quest to make these monsters reaches back more than a century. In the 1890s an English biologist named William Bateson catalogued every sort of hereditary variation known to science. Bateson was particularly struck by animals that were born with a body part in the wrong place. A spiny lobster had an antenna where its eye should have been. A moth grew wings instead of legs. Sawflies had legs for antennae. Among these monsters, there were even some humans. On rare occasion, people are born with little ribs sprouting from the neck, or an extra pair of nipples.

Somehow, these mutations were able to construct an entire body part in a place where it didn’t belong. Bateson called the process that created these freakish variations “homeosis.” The first clue to how homeosis works came in 1915, when Calvin Bridges of Columbia University traced a case to a particular mutation. He discovered mutant fruit flies that grew an extra pair of wings. These double-winged flies passed down their mutant gene to their doublewinged offspring, Bridges discovered; ever since, geneticists have kept their descendants alive.

Yet it wasn’t until the 1980s that biologists finally figured out how to isolate the gene that was responsible for Bridges’s mutants. They discovered that it was only one of an entire family of related genes, which are now called Hox genes. Biologists found that by altering other Hox genes, they could create equally grotesque flies, with legs sprouting out of their heads or antennae where their legs had been.

By studying these sorts of mutants, biologists were able to figure out how normal Hox genes work. Hox genes become active early in a fly embryo’s development, when it still assumes a nondescript football shape. The embryo begins to divide into segments, and although the segments all look identical, each is already fated to become a particular part of the fly’s body. It’s the job of Hox genes to tell the cells in each segment what they are going to become, whether they will become part of the abdomen or a leg, a wing, or an antenna.

Hox genes exert their power by acting like master control switches for other genes. A single Hox gene can trigger a chain reaction of many other genes, which together form a particular part of the body. If a Hox gene gets mutated, it can no longer command those genes properly. The error may end up making the segment grow a different body part. That was the secret of Calvin Bridges’s double-winged flies.

Hox genes are surprisingly elegant. Biologists can tell which cells in a fruit fly larva have active Hox genes inside them by making them glow. They inject special light-producing proteins that bind with the proteins produced by Hox genes. The glow of each Hox gene marks a distinct band of segments. Some Hox genes are active in the segments near the head of a fly, while others switch on in segments closer to the tail. Remarkably, the Hox genes themselves reflect this head-to-tail order: they are lined up on their chromosome in the same order as they are expressed in a fruit fly larva, with the head genes in front and the tail genes at the end.

When biologists first discovered Hox genes in fruit flies in the 1980s, they knew almost nothing about how genes control the development of embryos. They were overjoyed to be able to study the process even in a single species. But they assumed that the genes that built fruit flies would be peculiar to insects and other arthropods. Other animals don’t have the segmented exoskeleton of arthropods, so biologists assumed that their very different bodies must be built by very different genes.

Joy turned to shock when biologists began to find Hox genes in other animals—in frogs, mice, and humans; in velvet worms, barnacles, and starfish. In every case, parts of their Hox genes were almost identical, regardless of the animal that carried them. And the genes were even lined up in the chromosomes of these animals in the same head-to-tail order as they are in a fly.

Biologists discovered that the Hox genes did the same job in all of these animals: specifying different sections of their head-to-tail axis, just as they do in insects. Hox genes in these different animals are so similar that scientists can replace a defective Hox gene in a fruit fly with the corresponding Hox gene from a mouse, and the fly will still grow its proper body parts. Even though mice and fruit flies diverged from a common ancestor more than 600 million years ago, the gene can still exert its power.

In the 1980s and 1990s, scientists discovered many other master-control genes at work in animal larvae, each just as powerful as Hox genes. While Hox genes work from head to tail, other genes mark out the left and right sides of the body, and still others establish top and bottom. The three dimensions of fruit fly legs are mapped out by master-control genes as well. Master-control genes help build organs. Without the Pax-6 gene, a fly is born without eyes. Without the tinman gene, a fruit fly has no heart.

And just as with Hox genes, each of these master-control genes also exists in our own DNA, often doing the same jobs they do in flies. A mouse version of Pax-6, for example, can cover a fly’s body with extra eyes. As biologists explore the genes of other animals whether they are acorn worms or sea urchins, squid or spiders—they are finding that they share these master-control genes as well.

Master-control genes are able to use the same body-building instructions to build very different kinds of animal bodies. A crab’s legs are hollow cylinders with muscles running along their interior. Our own legs have a beam of bone at their core, and muscles running along their exterior. But crabs and humans still share many master-control genes for building limbs. The same goes for eyes, even though a human eye is a single ball of translucent jelly with an adjustable pupil, while a fly has hundreds of compound eyes that together form an image. A human heart is a set of chambers that sends blood coursing into the lungs and back into the body, while a fly’s heart is a tubular two-way pump. In all these cases, the master genes that help build them are the same.

This common genetic tool kit is so intricate that it could not have evolved independently in every lineage that uses it. It must have evolved in the common ancestor of these animals. Only after that common ancestor gave rise to the different animal lineages did the master-control genes begin to control different kinds of body parts. Yet as different as these animals became, their tool kit barely changed over hundreds of million years. That is why the master-control genes from a mouse can build a fruit fly’s eye.

Once biologists discovered the genetic tool kit, they realized that it might have made the Cambrian explosion possible 535 million years ago. The first animals to appear in the fossil records include primitive animals such as jellyfish and sponges—diploblasts whose embryos form from only two layers. Biologists have looked for master-control genes in these animals as well but have mostly been disappointed. Diploblasts have only a handful of these genes and don’t seem to use them in the same tightly organized way that triploblasts do.

That’s not surprising when you consider the simplicity of the jellyfish’s body. It does not have a body axis with left and right sides. Instead, its body is radially symmetrical, like a bell or a sphere. Its mouth is also its anus. Its nervous system is a decentralized web, rather than branches running off a central cord. It does not have the complex organization of a lobster or a swordfish.

Only after the primitive diploblasts branched off on their own did the genetic tool kit emerge in the common ancestor of all other animals. It made more complex bodies possible in these new animals: they could set up a grid of coordinates in a developing embryo, dividing the body into more parts, more sensory organs, more cells for digesting food or making hormones, more muscles for moving through the ocean.