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News Butterfly Effect - Single gene deletion could trigger random genome mutations

Article in 'News' Written by Arul Prakash Published Nov 14, 2013

  1. It might not be butterflies flapping their wings to cause a storm but it is close enough. Researchers from Johns Hopkins have revealed that a single gene deletion could trigger a phenomenon where the genome of the organism compensates with further mutations.

    In a paper to be published on the Molecular Cell journal, researchers have shown that single gene deletion from yeast genome triggers mutations elsewhere in another gene.

    This discovery certainly provides evidence to the belief that each gene in a genome is part of an intricate structure of information and any single gene deletion could cause damage to entire structure. Even though the study used yeast genome it is certainly applicable to human genetics, as DNA is conserved across species.

    "The deletion of any given gene usually results in one, or sometimes two, specific genes being 'warped' in response," said Dr. J. Marie Hardwick, a professor from David Bodian Professor of Molecular Microbiology and Immunology at Johns Hopkins. "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 added that researchers should pay closer attention to analysis and not blame genes for triggering a secondary mutation.
    Deletion of Gene B causes instability in the genome that is compensated for through a secondary mutation in Gene A,

    “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 yeast will help to identify these ‘first’ mutations in tumors.”

    The team preferred yeast as it was easier to knock out genes, an important aspect of their study. Where yeast with different knocked out genes were grown with the team trying to find, whether all the different single-gene knockout strains of yeast had similar genetic sequences as presumed. In total the team tested 250 different single-gene knockout strains, with six-strains to each strain.

    The sub-strains were put through a stress test, while they grew well at normal temperature some sub-strains couldn't grow when the temperature was increased. Genetic analysis of the faltered sub-strains revealed mutations in addition to the deleted gene. This prompted the team to scale the tests to 5,000 single-gene knockout strains and the results indicated 77 percent of all the single-gene knockout strains had one or more mutations that affected growth and survival.

    Hardwick believes that stressing yeast in other ways may lead to an even higher percentage of double-mutant strains. In fact, she said she believes that “essentially any gene, when mutated, has the power to alter other genes in the genome." Deleting the first gene seems to cause a biological imbalance that is sufficient to provoke additional adaptive genetic changes, she explains.

    Furthermore, in all of the strains that they examined, they found that the secondary mutations that appeared after a given knockout were always in the same one or two genes as in their earlier observations. Unexpectedly, Hardwick said, the altered growth of the sub-strains was usually due to the secondary mutations, not the original knockout, and many of those secondary mutations were in genes that are known to be cancer-causing in humans.
    • Arul Prakash

      Article by Arul Prakash

      Editor and founder of BiotechCareer.Org. He is an Industrial Biotechnologists and also a web developer, gooner, blogger, and foodie.

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