Avoiding unwanted genetic baggage

April 2019

The tool of choice for engineering crop plant DNA (be it transgenesis or gene editing) uses a plant pathogen, the bacterium Agrobacterium tumefaciens, as the vector.

Wild-type Agrobacterium naturally introduces its own DNA into the plant genome for the purpose of creating a gall (tumour) of plant tissue in which the bacterium can live. Genetic engineers create a GM Agrobacterium, has had its gall-inducing DNA removed and replaced with gene-editing DNA which therefore becomes inserted into the plant instead.

Despite the number of decades Agrobacterium has been in used for the genetic transformation of food and feed, and despite the recognition that such DNA insertion is error-prone, and despite the regulatory need for knowledge of the exact DNA alterations in the GM crops being assessed, the techniques for fully documenting the presence of unwanted changes have only recently become available.

Add to this, the recent rising realisation that there's a whole non-permanent but heritable layer of DNA-associated structures (proteins and biochemicals) collectively referred to as the "epigenome" which govern the function and integrity of DNA, and which also suffer change when Agrobacterium struts its stuff.

Early this year, a paper was published describing a detailed and unprecedented investigation of the genome and epigenomic status of four, randomly chosen Agrobacterium-transformed model GM plants*.

The study found multiple DNA insertions, deletions, truncations, rearrangements, inversions, translocations, duplications, and potential 'hairpins' (when DNA sticks to itself).

Less easy to identify are epigenetic effects of Agrobacterium-transformation, which "are largely uncharted territory". However, the study found "a strong impact" of the novel DNA construct on its supporting protein, suggesting serious implications for the plant's vital DNA damage responses in addition to effects on the expression of its DNA.

The researchers' press release announced that "New technologies enable better-than-ever details on genetically modified plants" offering "new ways to more effectively minimise potential off-target effects" and develop "modern crop plants without the unwanted genetic baggage of natural breeding". This seems to be a desperate attempt to put a positive spin on a paper which, in reality, describes how new DNA analytical techniques enable better-than-ever identification of the true extent and nature of the havoc caused by the DNA manipulation. At best it suggests a way to enable the most damaged GM lines to be discarded more efficiently.

GM Watch commented that using "the metaphors of scissors or a scalpel to imply that (genetic modification) methods are precise and targetted" should, on the basis of this study, more accurately be amended to that of "a chainsaw in the hands of a young child".

OUR COMMENT

It's a step in the right direction that the genome is no longer presented as a fixed string of base units with a fixed predictable function, but is described in terms of a complex DNA/protein architecture whose DNA operates within an epigenomic landscape.

The study, however, raises some very fundamental concerns. The science of gene function has largely been based on the study of GM plants. With such evident collateral DNA and epigenetic distortions present in their test GM plants, what on earth have geneticists actually been studying? The use of GM model cells has become a standard technique in many laboratories researching, for example, disease processes and drugs: how robust is the science emerging from these scientific facilities? On the back of all this questionable genetic 'science', the whole massive biotech industry has moved to feed the world with GM food and feed.

These results make it very clear that the GM process must be regulated for safety, and not just the expected or assumed final product. It might be good to bring this study and its obvious implications to the attention of your regulators, because the biotech industry lobby is trying its hardest to persuade them to ditch process-based regulation.

Some of that "unwanted genetic baggage" so despised by biotech scientists might just be vital for crop robustness and resilience. Check out LET'S THINK OMNIGENICS - April 2019

* The laboratory model plant is 'Arabidopsis', a simple, tiny plant extensively used for experimental purposes.

SOURCES:

• Florian Jupe, et al., January 2019, The complex architecture and epigenomic impact of plant T-DNA insertions, PLOS Genetics
• Leonardo Mariňo-Ramirez, et al., October 2005, Histone structure and nucleosome stability, Expert Review of Proteomics
• New technologies enable better-than-ever details on genetically modified plants, News Release, Salk Institute, 18.01.19
• New research confirms GM causes off-target damage to plant genomes, GM Watch, 28.01.19

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