JOIN USShared ancestry
Edward Marcotte is looking for drugs that can kill tumours by stopping blood vessel growth, and he and his colleagues at the University of Texas at Austin recently found some good targets, five human genes that are essential for that growth. Now they’re hunting for drugs that can stop those genes from working. Strangely, though, Dr Marcotte did not discover the new genes in the human genome, nor in lab mice or even fruit flies. He and his colleagues found the genes in yeast.
“On the face of it, it’s just crazy,” Marcotte said. After all, these single-cell fungi don’t make blood vessels. They don’t even make blood. In yeast, it turns out, these five genes work together on a completely unrelated task: fixing cell walls.
Crazier still, Marcotte and his colleagues have discovered hundreds of other genes involved in human disorders by looking at distantly related species. They have found genes associated with deafness in plants, and genes associated with breast cancer in nematode worms. The researchers reported their results in The Proceedings of the National Academy of Sciences.
The scientists took advantage of a peculiar feature of our evolutionary history. In our distant, amoeba-like ancestors, clusters of genes were already forming to work together on building cell walls and on other very basic tasks essential to life. Many of those genes still work together in those same clusters, over a billion years later, but on different tasks in different organisms.
Bat’s wing and a human hand
Anatomists in the mid-1800s were fascinated by the underlying similarities of traits in different species, the fact that a bat’s wing, has all the same parts as a human hand. Darwin argued that this kind of similarity, known as homology, was a matter of genealogy. Bats and humans share a common ancestor, and thus they inherited limbs with five digits.
Some 150 years of research have amply confirmed Darwin’s insight. Paleontologists have brought ambiguous homologies into sharp focus with the discovery of transitional fossils.
When scientists started sequencing DNA, they were able to find homologies between genes as well. From generation to generation, genes sometimes get accidentally copied. Each copy goes on to pick up unique mutations. But their sequence remains similar enough to reveal their shared ancestry.
A trait like an arm is encoded in many genes, which cooperate with one another to build it. In a 1997 paper, Sean Carroll of the University of Wisconsin, Neil Shubin of the University of Chicago and Cliff Tabin of Harvard Medical School coined a term for these borrowed modules: “deep homology.”
Deep homology
Since then, scientists have gotten a far more detailed look at many examples of deep homology. Dr Carroll and colleagues recently figured out how the spots on a fly’s wing evolved through rewiring modules. A tiny fly called Drosophila guttifera sports a distinctive pattern of 16 polka dots on its wings. Carroll and his colleagues discovered that the module of genes that sets the location of the spots is the same module that lays out the veins and sensory organs in the wings of many fly species. The module was later borrowed in Drosophila guttifera to lay down dots, too.
Our own eyes are the product of deep homology. The light-sensing organs of jellyfish seem very different from our eyes, but both use the same module of genes to build light-catching molecules.
Scientists are also discovering that our nervous system shares an even deeper homology with single-celled organisms. Neurons communicate with each other by forming connections called synapses. The neurons use a network of genes to build a complete scaffolding to support the synapse. In February, Alexandre Alie and Michael Manuel of the National Center for Scientific Research in France reported finding 13 of these scaffold-building genes in single-celled relatives of animals known as choanoflagellates.
No one is sure what choanoflagellates use these neuron-building genes for. The one thing that is certain is that they don’t build neurons with them.
Scientists have identified thousands of genes that can give rise to diseases in humans when they mutate. Other researchers have systematically mutated each of the 6,600 genes in yeast and observed how the mutant yeast fare under different conditions.
Marcotte and his colleagues amassed a database of 1,923 associations between genes and diseases in humans. They added over 100,000 additional associations between genes and traits in species including mice, yeast and nematode worms.
The scientists then searched for related genes that produced different traits in different species. Discovering these shared genes then allowed Marcotte and his colleagues to make new discoveries. Their database had a total of 67 genes that fix cell walls in yeast. If yeast and humans inherited an ancient gene module, we might use related versions of other yeast genes to build blood vessels.
The scientists studied the 62 other wall-fixing yeast genes. They discovered that five of the additional yeast genes also made proteins found in developing blood vessels.
Link with plants
Marcotte wondered if humans might also share modules with much more distantly related organisms: plants. He and his colleagues expanded their database with 22,921 associations between genes and traits scientists have found in the mustard plant Arabidopsis thaliana.
To their surprise, the scientists discovered 48 modules shared by plants and people. Scientists picked out one particularly strange module shared by plants and people for closer study. In humans, the genes have been linked to a rare genetic disorder called Waardenburg syndrome. It is caused by a disturbance in a group of cells in embryos called neural crest cells. Normally, the neural crest cells crawl through the embryo and form a strip running along the back. They then give rise to nerve cells, pigment-producing cells and some bones of the skull. People with Waardenburg syndrome have symptoms scattered across parts of the body produced by neural crest cells. They may include deafness; a white forelock of hair; and white patches on their face.
The scientists discovered that two Waardenburg-linked genes matched mustard plant genes for sensing gravity. If these genes are disabled by a mutation, a plant can’t grow upright.
Note:
* Edward Marcotte and his team at University of Texas found five human genes essential for blood vessel growth in yeast.
* He and his team have found genes associated with deafness in plants, and genes associated with breast cancer in nematode worms.
* Their database had a total of 67 genes that fix cell walls in yeast.
* Scientists discovered that two Waardenburg-linked genes (a rare syndrome in human beings) matched mustard plant genes for sensing gravity.