September 23, 1999 -- There would seem to be little connection between roundworm reproduction and human kidney disease, yet HHMI investigators have found such a link.
Paul Sternberg, an HHMI investigator at the California Institute of Technology, and colleague Maureen Barr had been studying the mating behavior of the tiny roundworm, Caenorhabditis elegans, when they found that a gene crucial to roundworm mating strongly resembles a gene involved in polycystic kidney disease.
"We set out to study how genes control neurons that control behavior," Sternberg said. To understand how genes influence reproductive behaviors, Sternberg and Barr introduced mutations into the roundworm's genome and then looked for males that had difficulty mating.
Reproduction in C. elegans involves two sexes, males and hermaphrodites. Hermaphrodites are females that produce sperm, which the hermaphrodite worm can use to self-fertilize the first 300 or so eggs. After self-fertilizing the first batch of eggs, the hermaphrodite preferentially accepts sperm from males in hopes of producing a larger number of offspring. This unusual mating system makes males nonessential, which is convenient for molecular biologists because it allows them to mutate males without altering the viability of the test strain.
When a male roundworm encounters a hermaphrodite, he places his tail, which contains sensory structures, flush with the hermaphrodite's body and glides it along the length of her body until he locates the vulva. After observing mutant worms under a microscope for many hours, Barr noticed that some males glided right past the vulva. Closer observation revealed that many of these mutants did not respond to the hermaphrodites at all.