The ancestors of humans and sea slugs diverged more than a half billion years ago, but scientists have now unexpectedly found genes that are remarkably similar in the brains of both. These findings could help shed light on the evolution of the brain in the animal kingdom and the mechanisms of human disorders such as Alzheimer's disease.

The sea slug Aplysia californica, a red, green or brown hermaphrodite that can grow up to 16 inches long, has the biggest brain cells, or neurons, in the animal kingdom, at up to a millimeter long. These marine snails also have just 20,000 or so neurons, compared with the 100 billion in people.

The small numbers and large sizes of brain cells in sea slugs make the animals ideal for brain research. Indeed, neuroscientist Eric Kandel of Columbia University shared the 2000 Nobel Prize in Physiology or Medicine for research in the snails that shed light on how memories form. Despite this groundbreaking work, much remains to be discovered about the genes that determine the function of neurons.

"Little is known even about what genes distinguish one neuron from another, even though they might perform quite different functions," Kandel says.

Kandel and Leonid Moroz of the University of Florida teamed up with other researchers to methodically identify genes expressed in Aplysia brains. They found that at any given time, more than 10,000 genes could be active within a sea slug brain cell.

Surprisingly, even though humans and sea slugs are separated by more than 530 million years of evolution, "Aplysia is similar to humans, more so than humans are with flies and worms," Kandel says.

For instance, when the researchers analyzed 146 human genes implicated in 168 neurological disorders, including Alzheimer's and Parkinson's diseases, they found 104 counterpart genes in the sea slugs. "The fact that a lot of genes are involved in similar neural activities in sea slugs and humans suggests the exciting possibility of further investigating neurological diseases such as Alzheimer's," says neuroscientist Dennis Steindler, executive director of the University of Florida's McKnight Brain Institute.

Scientists had assumed that many genes present in humans and absent in worms and flies had evolved recently in our lineage, "but some of these genes have now been found in Aplysia, which means that they are actually quite primitive," says neuroscientist Edgar Walters of the University of Texas Medical School at Houston. These new findings suggest modern animals had a common ancestor with a surprisingly complex genome, whose descendants subsequently kept or lost various genes.

Kandel, Moroz and their colleagues reported their findings in the December 29 Cell.