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Debate: Epigenetics

There is more to heritable changes than DNA - but does this make transgenic plants unsafe?

Our concept of genes has changed. It is far more complex than was thought just a few years ago. How genes are regulated and how they influence the characteristics of an organism as a result is not determined in the DNA alone. Other structures are also involved. Our knowledge of genes and their regulation is increasing rapidly. But what does this mean for the safety of transgenic plants? Does this realisation of greater complexity mean that the consequences of genetic modifications are less predictable? GMO Safety discussed this issue with two experts.

Dr Jens Freitag , head of the GABI agency (Genome Analysis of the Plant Biological System). “Epigenetic effects occur with every hybridisation.”

Katja Moch , Öko-Institut Freiburg: “The new findings have yet to be incorporated into the risk assessment of transgenic plants.”

Genes are the “blueprint for life”, DNA the letters in the “book of life”. Just a few years ago these concepts were taken for granted as a means of describing the “power of genes”. A single gene: a clearly defined segment of the infinitely long DNA chain which codes for a specific protein.

This “genetic determinism” is now considered to be out of date. Recent findings in molecular biology have significantly altered our concept of the “gene”. What had long been suspected is now a widely accepted scientific fact: it is not these “protein-coding genes” alone which determine an organism, and the processes which take place within it.

  • For a long time the function of the non-coding sections of DNA (“junk DNA”) could not be logically explained. But it has recently been discovered that they contain numerous “RNA-only genes”. However, unlike messenger RNA, this RNA intervenes in the regulation and behaviour of genes in different ways, rather than transmitting DNA to the protein-producing ribosomes. All available RNAs are referred to collectively as a transcriptome. This constitutes a complex, autonomous layer between the genome and protein synthesis, which is involved in diverse interactions.
  • We also know now that DNA is not alone in determining whether and when genes are switched on and off. Low-molecular substances, such as RNA fragments, or slight modifications to the DNA (e.g. methylation) can influence gene regulation. Other substances which are implicated in gene regulation affect the support structure of the DNA molecule and modify the chromosome structure (chromatin remodelling). These types of modification in gene expression, which are not attributable to DNA determination, are described as “epigenetic”. Genes can be silenced using epigenetic controls, and can also be re-activated by modifying the epigenetic structures. We are now beginning to understand the vital role that these epigenetic phenomena play in many processes within the cell and also in inheritance.

Epigenetic phenomena - A particular problem for transgenic plants?

It is clear that genes are not alone in determining how an organism develops. The genome is not a DNA code which we need only decipher in order to understand its function. It is in fact a three-dimensional, biochemical machine of immense complexity.

Everything is more complex and multi-layered than was thought just a few years ago - but what does this mean for transgenic plants? Do these new discoveries about epigenetics and gene regulation mean that the introduction of new genes could have knock-on effects which as yet we know nothing about? Are current procedures for the safety assessment of genetically modified plants still suitable? Or should they be widened to take account of changes triggered by epigenetic processes or structures which may be problematic from a safety perspective?

The scientific community has already begun to debate these issues. In essence, and in very simple terms, there are two positions.

  • The first perspective makes a fundamental distinction between genetic procedures – the integration of new genes into the genome – and other methods used in plant breeding. Epigenetic findings are regarded as confirmation of this viewpoint: Since it is not normally possible to determine accurately at what location in a genome the new gene will be integrated, non-coding gene regions can be affected. This could result in modified transcripts. It is also conceivable that a new gene could be controlled by epigenetic structures in the plant, making it behave in ways that were not intended. It is speculated that, as a rule, current safety assessment procedures are not able to identify these effects and their consequences.
  • The second viewpoint points out that epigenetic phenomena have always occurred in plant breeding. The only difference is that we now know about them. The processes themselves have always existed, and they are not restricted to genetically modified plants. On the contrary: Plant breeders know from experience that modified traits which are not solely determined by the genes from the two parent lines occur in new varieties. Today we can interpret these observations as epigenetic processes. With modern molecular biological or chemical analyses it is possible to determine accurately how individual strains or varieties deviate from one another. Unlike traditionally bred plants, transgenic ones are examined in great detail on the basis of different chemical, genetic or phenotypical characteristics to find out whether they are “substantially equivalent” to conventional reference plants. Although not all epigenetic events and effects are known, the changes they bring about will be detected using standard safety assessment procedures. There is no question that the new image of genes and the growing body of knowledge about transcriptomes and epigenomes have far-reaching consequences for research and for the ongoing development of genetic engineering methods. However, a fundamental change to the safety assessment of transgenic plants is not needed.

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