Phenomena
responsible for disturbances
in gene expressionaccording to research at the John Innes Centre (This is a leading European plant science research
center in UK) [ The term “transgenic” used below means “genetically ingeneered”] These disturbances include: Ÿ Position effects - arising from the insertion of "alien gene sequences into random locations" Explanation: This means that the position where the gene is inserted, influences its effects (its “expression”). Ÿ Promoter methylation - because "plants do not readily take up and incorporate 'invading DNA' into the genome" Explanation: This means that an important component, the promoter in the inserted complex becomes blocked. Without the promoter, the inserted gene remains silent. Ÿ Inter-loci interactions - including "co-suppression where a transgene can modify the action of an endogenous gene, and interaction between transgenes when one transgene construct can modify the action of another" Explanation: The inserted gene can influence other genes. This may lead to unpredictable and unexpected effects including the creation of undesired or unexpected substances which in the worst case may be harmful. Ÿ Gene silencing - where transgenes "can be unstable and become silenced" [ie switched off] Explanation: There are strong protection mechanisms against the uptake of foreign genes. These may silence the inserted gene or may make it unstable. Ÿ Sequence homology - where transgene constructs interact with one another, which "may inactivate the expression of another construct in the same plant" Explanation: Parts of the inserted gene can inactivate other inserted genes. Ÿ Heteroencapsidation - assisting "long distance viral movement around infected plants" and possibly enhancing "the movement of a superinfecting virus that did not normally move systemically". Heteroencapsidation can take place between "viruses of the same group, and between unrelated viruses." Explanation: New viruses can be generated. Work at the JIC further confirms: Ÿ Transgenes can have very high levels of instability Ÿ Transgenes "frequently show considerable variation" in expression Ÿ Trangenes "can interact with resident genes, and with other transgenes" Ÿ Transgenes can "influence characteristics apparently unrelated to the function of the transgene" Ÿ "Most transgenic constructs contain some genetic sequences from plant pathogens" Ÿ Transgene expression can be significantly affected by environmental influences Ÿ Transgenes subsequently transferred sexually [i.e. by conventional pollination] into different genetic background can "vary in expression, stability and pattern of inheritance" Ÿ "The precise cause of interaction between transgenes and the background genotype is not known." Ÿ "Transgenes can show abnormal tissue specificity and expression can vary through plant development and inheritance..." Ÿ "Trangenes can display abnormal inheritance" Ÿ "Transgenes or parts of them can be lost" Ÿ Transgene silencing may lead to activation of allergens and toxins which other elements of the modification process have been designed to suppress Ÿ "It is common to observe substantial variation between transgene expression in independently transformed plants" Ÿ "Where their is homology [sequence compatibility] between trangenes and resident genes there is likely to be some interaction." Homology may result in "no native or transgene expression." Ÿ Where multi-construct transgenic plants are reproduced sexually constructs may become separated by segregation in subsequent generations where "it is possible that a formerly silenced or poorly expressing construct may become more highly expressed in subsequent generations" Amongst other matters the JIC advises: Ÿ "It is possible that a rare event may have insignificant consequences when transgenic crops are grown on a small experimental scale, but become more important when transgenic crops are grown over thousands of hectares." [PSRAST comment, see our explanation of the gene lottery] Ÿ "The area of concern specific to viral transgenes is the potential risks on any interactions between the viral or virus-related sequences being expressed from the transgene and another virus superinfecting that plant" Ÿ "There is considerable evidence for extensive recombination in RNA viruses.... It is generally considered that recombination plays an important role in the evolution of RNA viruses. Evidence is now forthcoming of recombination between superinfecting viral RNA and RNA expressed from a transgene through the aberrant homologous recombination mechanism. The finding of recognizable host RNA sequences within viral RNAs is suggestive of nonhomologous recombination." [i.e. this section refers to the unintended creation of new plant viruses in certain types of transgenic plants] Ÿ Specifically in relation to crops genetically modified for viral resistance, (although recombination events are not confined to them) -: "It is difficult to devise detailed protocols in the field for the detection of recombinants produced in the field..... For small scale-releases, it is relatively easy to design monitoring procedures.... This will be much more difficult, if not impossible, for large-scale releases, in which the approach should be to educate farmers and extension personnel to identify any unusual event that might be associated with transgenic plants. This will be the challenge of the future...." Ÿ "Recent research in our laboratory with Brassica napus plants containing the 35S promoter from the mosaic virus (CaMV) has shown that upon infection with the CaMV the driven transgene is silenced (Al-Kaff et al unpublished). Intensive research at present is directed towards understanding this silencing mechanism and its significance. As the 35S promoter is widely used to regulate transgenics in brassicas, it is important that we strive to obtain a clear understanding of the mechanisms of this silencing and its significance. This is important for two reasons, for assessing the use of the 35S promoter in agriculture and also for assessing the significance of this effect for biosafety."[our emphasis; also note this promoter is used in most other transgenic plants as well, including those already released into the environment] Ÿ "An understanding of the causes of transgene stability and expression is important for various reasons [including]...for assessing their potential impacts on human health and the environment.........A knowledge of transgene stability, expression and inheritance is fundamental for the successful and safe use of transgenes in large scale agricultural production. Many factors influence the ways in which transgenes express, but a factor of crucial importance is the effect of DNA sequences that are homologous to areas of transgene constructs. For those concerned with the development of transgenic brassicas [ie oilseed rape etc] the take home message from this paper is 'watch out for homology.'" [our emphasis; note the paper makes clear that such phenomena are similarly relevant to other types of transgenic crops.] This text was modified from Appendix A in the report by NLP Wessex about the “OECD Edinburgh conference”.
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