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Deletion of any single gene provokes mutations elsewhere in the genome
Date:11/13/2013

Johns Hopkins researchers report that the deletion of any single gene in yeast cells puts pressure on the organism's genome to compensate, leading to a mutation in another gene. Their discovery, which is likely applicable to human genetics because of the way DNA is conserved across species, could have significant consequences for the way genetic analysis is done in cancer and other areas of research, they say.

Summarized in a report to be published on Nov. 21 in the journal Molecular Cell, the team's results add new evidence that genomes, the sum total of species' genes, are like supremely intricate machines, in that the removal of a single, tiny part stresses the whole mechanism and might cause another part to warp elsewhere to fill in for the missing part.

"The deletion of any given gene usually results in one, or sometimes two, specific genes being 'warped' in response," says J. Marie Hardwick, Ph.D., the David Bodian Professor of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health and a professor of pharmacology and molecular sciences at the school of medicine. "Pairing the originally deleted gene with the gene that was secondarily mutated gave us a list of gene interactions that were largely unknown before."

Hardwick says the findings call researchers to greater scrutiny in their genetic analyses because they could unwittingly attribute a phenomenon to a gene they mutated, when it is actually due to a secondary mutation.

"This work has the potential to transform the field of cancer genetics," Hardwick says. "We had been thinking of cancer as progressing from an initial mutation in a tumor-suppressor gene, followed by additional mutations that help the cancer thrive. Our work provides hard evidence that a single one of those 'additional mutations' might come first and actively provoke the mutations seen in tumor-suppressor genes. We hope that our findings in yeas
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Contact: Catherine Kolf
ckolf@jhmi.edu
443-287-2251
Johns Hopkins Medicine
Source:Eurekalert  

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