Science in Society Archive

Synthetic Genes in Food Crops

Prof. Joe Cummins explains why genes inserted into GM crops are not "substantially equivalent" to genes in their native state

In North America, genetically modified (GM) foods unlabeled and untested are taking over the food supply. Such foods are promoted on the fiction that the foreign genes - usually taken from bacteria and viruses - inserted into GM crops are "substantially equivalent " to the natural genes.

In reality, the genes used to create GM crops are synthetic approximations of the natural genes. They contain synthetic DNA sequences tuned to maximize production of foreign proteins in the plant, such as toxins killing insects or enzymes degrading herbicides, which also provide firm patent protection on the GM crop. Synthetic genes are used because the genes actively expressed in bacteria or humans are not very active in crop plants. There are several ways to solve the problem.

The first is to adjust the DNA code to suit the ‘codon bias’ typical of the crop plant species into which genes from bacteria or mammals are introduced.

The genetic code is made up of 64 three letter codons (triplets, or code words) for twenty amino acids plus words for translation start and stop. Some amino acid such as methionine (met) and tryptophan (tryp) have only one codon, while arginine (arg), leucine (leu) and serine (ser) each have six codons. The degeneracy of the code allows for alternative DNA sequences for a single protein. The frequencies with which different codons are used vary between groups of organisms, which is why genes from bacteria are poorly read in higher plants (and vise versa). For optimum gene expression, the code for a transgene often needs to be rewritten to achieve adequate performance. The number of possible gene sequences that can code for a single protein is staggering, it is estimated to be about five times ten to the 47th power [1]. That number is within three orders of magnitude of the number of atoms making up earth and five times larger than the number of water molecules on earth [2]. In synthesizing the genes used in GM crops, say, in altering a Bacillus thuringiensis (Bt) Cry toxin gene for plants, a table of plant-preferred codons is used to substitute the plant preference for the bacterial preference [3].

Sometimes it is necessary to substitute one or more of the amino acids so that the final Cry toxin can function in the plant cell environment [3, 4]. As plant genetic engineering has "advanced", the crucial active domains of toxins and enzyme are defined and "improved" to such an extent that the original source protein from living organisms is hardly recognizable.

A third modification of the transgene is in the regulatory sequences (frequently referred to as cis elements) such as promoters, introns and transcription termination signals, which are usually taken from higher plants or their viral and bacterial pathogens. Synthetic promoters have also been created, loosely based on the cauliflower mosaic virus (CaMV) commonly used in plant genetic engineering [5].

The use of synthetic genes in food crops has not been taken into account sufficiently in the regulatory approval of the food crops. In spite of the obvious differences between the synthetic and the natural genes from which they arose, regulators have allowed the genes and proteins produced in bacteria to be considered appropriate surrogates in safety testing for the synthetic genes and the proteins produced in food crops [6]. This exposes the unhealthy collusion of corporations and their regulators [7, 8].

There seems to be a convenient fiction propagated by corporations, government bureaucrats and academics who depend on grant money from corporations and government, that genes from bacteria are used in producing food crops or that genes from humans are used to produced plant biopharmaceuticals, when, in fact, the genes used are synthetic approximations to the real things. Even the courts seem to have accepted this convenient fiction as fact.

The next generation of GM crops is evolving towards a minimal assembly of active protein domains (domains are active area of proteins that serve as signals for activates such as toxicity or enzyme function or environment sensors for regulation) that are frequently patched together from a number of different proteins. Safety testing is based, once again, on unreal surrogates and the products are not labeled in the marketplace so that subtle changes caused by a few amino acid changes or failure to heed secondary protein modifications such as glycosylation will be difficult to trace as people are adversely affected by consuming the synthetic products in GM crops.

It is imperative that the synthetic genes and their products be tested thoroughly, not only for potentially toxic side effects but for stability and recombination properties as well. These synthetic genes have not had an evolutionary history and it is a major mistake to assume that the genes can be expected to behave in all ways like the genes that they were built to represent.

Article first published 01/09/04


References

  1. Gustafsson C, Govindarajan S. and Minshull J. Codon bias and heterologous protein expression Trends in Biotechnology 2004, in press pp 1-8
  2. About Big Numbers qaearth =atoms in the earth 2004 http://pages.prodigy.net/jhonig/bignum/qaearth.html
  3. Fischoff D and Perlak F. Synthetic plant genes. 1996 United States Patent 5,500,365 pp1-59.
  4. Payne J, Cummings D, Cannon R, Narva K and Stelman S. Bacillus thuringiensis genes encoding lepidopteran-active toxins. 1998 United States Patent 5,723,758 pp 1-32
  5. Bhullar S, Chakravarthy S, Advani S, Datta S, Pental D and Burma P. Strategies for development of functionally equivalent promoters with minimum sequence homology for transgene expression in plants: cis-elements in a novel DNA context versus domain swapping. Plant Physiology 2003, 132, 988-98.
  6. Cummins J. Regulation by deceit. Science in Society 2004, 22, 32-3.
  7. Ho MW. DNA in food and feed. ISIS Report, 17 June 2004 https://www.i-sis.org.uk/GMDNAIF.php
  8. Ho MW. and Cummins J. GM food and feed not fit for "man or beast". ISIS Report, 7 May 2004 https://www.i-sis.org.uk/ManorBeast.php

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