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Why a Mutant Fungus is Blind

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Duke Health News 919-660-1306

DURHAM, N.C. -- The gene whose mutation renders a fungus "blind" to light has been discovered by Duke University Medical Center researchers. They said their finding -- which solves a genetic mystery four decades old -- could give basic insights into how organisms sense and respond to environmental signals. These signals include not just light, but also gravity, touch and chemicals.

The researchers identified the mutations in a particular strain of a filamentous fungus called Phycomyces, which scientists use to study sensory perception. The strain has an unidentified mutation called madA, which causes defects in phototropism, the growth of the fungus toward light.

The discovery of the specific mutated gene underlying the madA defect could signal a turning point in the field of sensory research, providing an avenue for other researchers to join in the pursuit of the remaining nine genes in the mad family, said the investigators.

The results of the Duke research appeared this week in the online edition of the Proceedings of the National Academy of Sciences, to be published in print in the March 21 issue of the journal. The work was supported by the National Institutes of Health.

"These organisms can sense all kinds of environmental stimuli – light, gravity, objects," said Joseph Heitman, MD, PhD, senior author of the study. "Their spore-containing branches respond by growing in a different direction or at a different speed in reaction to such stimuli."

Phycomyces mutants with defective phototropism were isolated in the laboratory of Nobel Laureate Max A. Delbrück, with the aim of identifying the components of the sensory pathway. Biologists named the phototropic mutants mad mutants in honor of Delbrück. Of the 10 mad mutants identified, three (madA, madB, and madC) have defective phototropism but react normally to gravity and other environmental signals.

"In 1953 Delbrück quit his research for which he won the Nobel Prize and worked the rest of his life on discovering the photoreceptors, or light-sensing proteins, in the fungus Phycomyces," said Duke's Alex Idnurm, Ph.D., first author of the study. "He never succeeded, though was still at it up until he died in 1981. In our paper, we identified one of the Phycomyces photoreceptors and show Delbrück's "blind" strains contain mutations in this gene."

Using genetic sequence information from the genes for photoreceptors of other fungi, the researchers identified two candidate light-sensing genes of similar sequence in Phycomyces. To determine whether either of these genes was required for light-sensing, the researchers determined the sequences of genes from Phycomyces strains that contain madA, madB, and madC mutations. They found mutations in one of the candidate genes in three separate madA mutant strains of Phycomyces. Further experiments showed that the mutant fungi did have a light-sensing defect that is directly attributable to the madA mutation.

Later this year the sequence of the Phycomyces genome will be completed. The researchers envisage that the complete sequence will facilitate the cloning of the other mad genes, further elucidate how the fungus responds to light, and eventually enable the discovery of the molecular basis by which other environmental signals are perceived.

Collaborators on the study include Julio Rodriguez-Romero and Luis Corrochano of the University of Seville; Catalina Sanz, Enrique Iturriaga, and Arturo Eslava of the University of Salamanca.

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