[Date Prev][Date Next][Thread Prev][Thread Next][Date Index][Thread Index]

[SANET-MG] synthetic genes in food crops



June 20, 2004

Prof. Joe Cummins

“Synthetic genes in the brave new world of food crops”

In North America genetically modified (GM) foods that are unlabeled and
untested are taking over the food supply. The promotion of such foods
maintained that natural genes “substantially equivalent “ to the genes
in normal crops were being shifted from bacteria or viruses to improve
food crops. That promotion ignores the reality of genetic technology.
The genes used to create GM crops are synthetic approximations of
natural genes that contain synthetic DNA sequences tuned to maximize
production of toxins killing insects or degrading herbicides, as well as
providing firm patent protection on the food crop. Synthetic genes are
used because the genes active in bacteria or man are not very active in
crop plants. The DNA code must be adjusted for 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 (code words) for
twenty amino acids (61 codons) plus words for translation start and
stop. The code words for protein amino acid are encoded for between one
(met and tryp) and six (arg,lue,ser) synonymous code words. The first
two positions of the codon are fixed for a particular amino acid while
the third position is said to wobble allowing for alternate code
letters. The degeneracy of the code allows for alternative gene codes
for a single protein, The frequency with which different codons are used
varies between groups of organisms, so for example, genes from bacteria
are poorly read in higher plants (and visa versa), For optimum
expression the code for a transgene frequently needs to be rewritten to
achieve adequate performance. The codon bias within members of a group
of organisms such as plants is believed to be caused by the presence of
typical isoacceptor transfer RNA families in the different groups of
organisms. The number of possible genes that can code one protein
molecule 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 useful activity in 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 recognized and
“improved” to such an extent that the original source protein from
living organisms is hardly recognizable.

Regulatory sequences (such genes are frequently referred to as cis
elements) such as promoters, introns and transcription termination
signals are normally are normally taken from higher plants or their
viruses. Nevertheless, progress has been made in creating synthetic
promoters 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. The synthetic
genes , based on bacterial genes or human genes, can be propagated in
bacteria using illegitimate recombination and bacterial plasmids but
such genes are not substantially active in those bacteria nor do they
readily participate in homologous recombination. The synthetic genes
lack DNA homology with the bacterial or human genes from which they
originated. The codon usage of humans and of bacteria diverges from the
codon preference of plants yeast and nematodes. The synthetic genes used
in crop plants do not function successfully in bacteria or humans but
should do well in yeast (and likely other fungi) and in nematodes. 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). The use of the bacterial surrogates has been to spare
corporations the cost of isolating the quantities of DNA and protein
from the crop plants needed for safety testing. That is true even though
the cost of fully testing the “real thing” is negligible relative to the
profits from licensing the GM food crops to farmers. The genes and their
proteins produced in bacteria are no real substitute for the real genes
and proteins produced from them in food crops and the assurances that
the safety tests are fully meaningful is a convenient fiction showing
the unhealthy togetherness 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 to promote the myth 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 in the
crop plants are synthetic approximations used to produce products
similar to the real thing. Even the courts seem to have accepted the
convenient fiction as if it were 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 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 effected by consuming the synthetic GM crops.

It is imperative that the synthetic genes and their real 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 gene that
they were built to represent. A distinction must be made between natural
genes and transgenes and the synthetic representations of those genes
used to manufacture GM crops. A polluting synthetic transgene should not
be presumed to be equivalent to a polluting natural transgene.

References

  1. Gustafsson,C,Govindarajan,S. and Minshull,J Codon bias and
     heterologous protein expression 2004 Trends in Biotechnology 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 2003
     Plant Physiology 132, . 988–98
  6. Cummins,J. Regulation by deceit 2004 Science in Society 22,32-3
  7. Ho,M DNA in food and feed 2004 ISIS press release pp1-8

http://www.i-sis.org.uk/

  8. Ho,M. and Cummins,J. GM food and feed not fit for “man or beast”
     2004 pp1-6

http://www.i-sis.org.uk/

********************************************************
To unsubscribe from SANET-MG:
1- Visit http://lists.sare.org/archives/sanet-mg.html to unsubscribe or;
2- Send a message to <listserv@sare.org> from the address subscribed to the list. Type "unsubscribe sanet-mg" in the body of the message.

Visit the SANET-MG archives at: http://lists.sare.org/archives/sanet-mg.html
For more information on grants and other resources available through the SARE program, please visit http://www.sare.org.