New Salk Institute Study Reveals More Detailed Picture of “Scrambled Nature” of Gene Insertions in GMOs

Plant molecular biologists have known for decades that the techniques they use to genetically engineer plants are error prone and can result in GMOs with unintended:

  • mutations in host plant genes,
  • insertion of vector backbone DNA sequences,
  • small duplications or deletions of inserted or host DNA, and/or
  • large rearrangements of host plant chromosomes.

Other unintended changes are also possible; for example, Monsanto’s commercially available NK603 corn unintentionally produces a hybrid RNA molecule derived from sequences of the foreign DNA inserted into that product and sequences from the recipient corn variety’s DNA adjacent to the insertion site.

But, according to the new study published by Jupe et al., “detailed understanding of structure and epigenomic status of insertion events [had been] limited” by the technologies available to researchers; “plant scientists didn’t have the molecular tools” that could enable them to “see” the multiple effects that inserting pieces of foreign DNA into a host plant’s genome have had on those genetically engineered (GE) genomes in a single “picture” until recently.

For this new study, conducted under the supervision of Joseph R. Ecker, a highly respected academic plant molecular biologist at the Salk Institute for Biological Studies, researchers used “state-of-the-art long-range sequencing technologies…to provide new insights into the structural impact of inserting foreign [DNA] fragments into plant genomes….”

These authors, primarily associated with the Salk Institute but including a scientist from the Donald Danforth Plant Science Center and two others from the J. Craig Venter Institute, utilized the state-of-the-art techniques to elucidate unintended changes in the genomes and epigenomes of Arabidopsis thaliana plants that had been genetically engineered using the Agrobacterium-based method. [Arabidopsis is a model plant organism used by many academic researchers. The Agrobacterium-based method of genetic engineering involves the intended transfer of a specific piece of DNA (the transferred DNA or “T-DNA”); this method is good enough at mutating host plant genes that it was used by plant scientists in an effort to mutate every gene in the Arabidopsis genome. Many commercially available GMOs were created using the Agrobacterium-based method of genetic engineering.]

The new study revealed the “scrambled nature of T-DNA and vector backbone insertions and rearrangements in high detail” and “uncovered various effects of T-DNA insertions on the adjacent chromatin landscape.” Unintended “intra- and interchromosomal rearrangements” were discovered, for example, as well as unintended “alterations of chromatin and thus chromatin structure and functionality.” With “unprecedented detail” this study reveals “novel insights into the impact of these events on plant genome/epigenome integrity.”

The authors point out that this kind of “Knowledge of structure variations induced by transgene insertions…as well as evidence for epigenetic changes to the host genome is crucial from scientific as well as regulatory perspectives.”

I agree. We just don’t know enough about genomes and epigenomes, and how randomly inserting foreign pieces of DNA into them and scrambling them will affect them. Therefore, I think U.S. regulators should take a more precautionary approach to regulating GMOs, and require developers of GMOs to provide information about the integrity of the genomes and epigenomes of their products prior to commercializing them.

But the FDA has never required developers of GMOs to provide the kind of crucial information about structure variations induced in their products by transgene insertions that Jupe et al. addresses…even though older techniques for revealing most of them have been available for decades. And some who have provided information about the “scrambled” genomes in their GMOs to the FDA voluntarily–like Monsanto did for NK603–have gone ahead and commercialized those scrambled products anyway.

Jupe et al. conclude the Discussion of their results by stating that “Our findings pave the way for structural genomic studies of transgenic crop plants….”

Maybe. But will developers of GMO crops follow this newly paved path? Will FDA make them?

Or will GMOs with scrambled genomes and epigenomes continue to be commercialized?

 

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