The full set of about 200 genes that control the separation of chromosomes during cell division in the Drosophila fly has been identified by researchers at UC San Francisco and UC Davis.

This is the first whole-genome analysis of such a complex cellular machine in a relatively advanced animal. It should form the basis for further studies of cell division in these and other animals and plants.

When a cell from a fly, a human or a plant divides, the chromosomes perform a tightly choreographed ballet so that each daughter cell ends up with the same DNA. From each end of the cell, filaments fan out to form a structure called the "metaphase spindle." These filaments attach to chromosomes and draw them back to the opposite ends of the cell.

The team, led by Gohta Goshima, a postdoctoral researcher with Professor Ronald Vale at UCSF, used RNA interference to individually block every known gene in Drosophila. Setting up dividing Drosophila cells in culture, Goshima looked for those that failed to make a proper spindle.

That search was done using an automated microscope that acquires one image per second to generate millions of images overall. To deal with this very large set of data, Roy Wollman, a graduate student working in the laboratory of Jonathan Scholey, professor of cell biology and biochemistry at UC Davis, wrote special software that "taught" the computer how to search for abnormal spindles within the images, which could then be examined in more detail by human eyes.

Altogether, the scan of all 14,425 fly genes looked at about four million spindles, yielding some 200 genes that directly affect spindle assembly. About a quarter of these genes were expected, but the rest were a surprise, Scholey said.

"This study uncovers a lot of genes that influence the spindle machinery, in some cases encoding proteins that interact with spindle microtubules, for example, and in other cases probably influencing spindle function indirectly. So mitosis may be more complicated than we thought," he said.

The paper was published in the April 20 issue of the journal Science. Goshima and Wollman began their collaboration while studying at the Marine Biological Laboratory at Woods Hole, Mass. Wollman was supported by a UC GREAT (Graduate Research and Education in Adaptive Biotechnology) grant, and is co-mentored by Scholey, Vale and Alex Mogilner of the UC Davis mathematics department.