Our distant cousin, the fly

Scientists looking across human, fly and worm genomes find shared choreography.

By: New York Times | Updated: September 7, 2014 12:46:00 am

In the early 1900s, scientists began studying Drosophila melanogaster, the common fruit fly. Research on these fast-breeding insects revealed that genes lie on chromosomes, which turned out to be true for other animals, including us. For more than a century, scientists have continued to glean clues from the fly to other mysteries of biology, like why we sleep and how heart disease develops.

In the 1960s, another unassuming animal joined biology’s pantheon: a tiny worm called Caenorhabditis elegans. Biologist Sydney Brenner realised that its body, made up of just a couple of thousand cells, offered a singular opportunity to learn how a single egg gives rise to a complete animal. Many scientists are now studying the worm for clues to how our own brains are wired.

Now the two species are providing even deeper insights. A team of hundreds of scientists has exhaustively recorded the choreography of their genes as the animals develop from eggs to adults.

“It’s not just this gene or that gene,” said Robert H Waterston, a geneticist at the University of Washington who is among the scientists working on the project, called modENCODE. “We can get a picture of the whole.”

Waterston and his colleagues published overviews of the modENCODE results last week in Nature. They found a striking similarity between the choreography of genes in flies and worms and that of our own DNA. Exploring that similarity may provide scientists new insights into genetic disorders and diseases like cancer.

In 1998, Waterston and a large group of fellow scientists catalogued all 19,000 protein-coding genes in C. elegans, along with a rough guide to the rest of its DNA. In 2000, researchers did the same for D. melanogaster. But these efforts revealed little about what the genes actually do in an organism.

Cellular DNA is coiled around spool-like molecules called histones. When DNA is tucked away, gene-reading molecules cannot reach it. By adding certain compounds, known as histone marks, to the histones, a cell opens up a stretch of DNA. When a gene is exposed this way, a protein called a transcription factor latches onto it, recruiting other molecules to “read” it and produce a new protein or RNA molecule.

To study genes in humans, the scientists focused on a wide variety of cells, like neurons, blood cells and liver cells and catalogued the parts of the genome that cells were using. They also mapped the histone marks and located the transcription factors latching onto the DNA. Because the scientists used the same methods to gather data from all three species, they were able to compare them on a scale never before attempted.

Flies, worms and humans come from distant branches on the evolutionary tree. The last common ancestor lived 700 million years ago.
In all three, it turned out, many genes tended to turn on and off in the same pattern. All told, the researchers found 16 such sets of genes, each containing hundreds of genes working together. While it’s not clear yet what these genes are doing in all three species, the scientists did observe that a dozen clusters were especially active at some stages of development in the worm and the fly. They may be essential for transforming an egg into an adult animal.

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