Deletion of Single Gene Leads to Mutation, Study Finds

cell

Researchers at John Hopkins University have discovered that the deletion of any single gene in yeast cells puts pressure on an organism to compensate, leading to a mutation in another gene within the genome – the organism’s genetic makeup.

The findings may have significant implications for genetic analysis in cancer as the ‘warping’ behavior identified in yeast cells is likely to be applicable to human genetics. The same genes that control the cell cycle in baker’s yeast, and that malfunction in tumor cells also exist in a similar capacity in human cells.

Yeast was used for research because of its nature to easily delete, or “knock out,” a gene within the organism’s genome. Hardwick’s team started the experiment with a collection of thousands of different yeast strains, each with a different gene knockout.

Growing each yeast strain at its preferred temperature, each strain grew robustly, despite missing a different gene. Upon examination, the team discovered that in addition to the originally knocked-out gene, each of the sub-strains that faltered also had a mutation in another gene. This led the team to conclude that the cells in each strain of the single-gene knockouts do not all share the same genetic sequence, as first thought.

Published in Molecular Cell, the findings of the study support existing evidence that an organism’s genetic makeup is like a complex and sensitive machine. The highlights taken from the report include:

  • Knockouts of the same gene evolve similarly without applied environmental pressure
  • Yeast knockouts harbor meaningful second mutations that challenge genetic analyses
  • Common assumptions about problems with yeast knockout collections are unlikely
  • First (engineered) and evolved yeast mutations also co-occur in human tumors

Professor of Molecular Microbiology and Immunology Dr. J. Marie Hardwick said:

“The deletion of any given gene usually results in one, or sometimes two, specific genes being ‘warped’ in response. Pairing the originally deleted gene with the gene that was secondarily mutated gave us a list of gene interactions that were largely unknown before.”

Researchers will now be under greater scrutiny in their methods of genetic analysis. They could unwittingly attribute a phenomenon to a gene they have mutated when the change is actually caused by a secondary mutation. Hardwick adds:

This work has the potential to transform the field of cancer genetics. 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.”

Notes:

Molecular Cell: Genome-wide Consequences for Deleting Any Single Gene

John Hopkins University’s Press Release: Deletion of Any Single Gene Provokes Mutations Elsewhere in the Genome

L. H. Hartwell’s Yeast: A Model Organism for Studying Somatic Mutations and Cancer

Image credit: with thanks to Sundstrom of RGB Free Stock

Advertisements