GENET archive


SCIENCE & GENES: One gene, one protein, one function - not so

                                  PART 1

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SOURCE: On Line Opinion, Australia

AUTHOR: Greg Revell


DATE:   12.12.2008

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With the abrupt and uninvited introduction of genetically modified (GM) food into our supermarkets and restaurants, many of us are looking more closely into the food we eat.

Recently, Monsanto?s apparent transformation from agrichemical giant to philanthropic institution was cynically trumpeted to the world?s media: ?We will double crops yields!? Such grandiose promises can only be offered if there is a parallel narrative that portrays genetic engineering as being able to permit the precise control of life processes and by extension, provide predictable and controllable agricultural outcomes.

The Biotechnology Industry Organization?s public relations campaign explains:

Through modern methods found in biotechnology, researchers can accomplish the desired results, but in a more efficient and predictable manner (than in conventional plant breeding). In this process, a specific gene, or blueprint of a trait, is isolated and removed from one organism then relocated into the DNA of another organism to replicate that similar trait (my emphasis).

But are the techniques that give rise to GM foods as precise and controlled as the PR blurb suggests?

First of all, the scientist has to identify a gene that he or she believes will confer a trait to another organism. Using chemical shears, the foreign gene is cut and pasted into a viral ?ferry?. Viruses are used because of their unique ability to transfer genetic material across species boundaries, which is usually required in most GM products. To this viral vector are attached controversial ?promoter? and ?antibiotic-resistant marker? genes.

The entire package is duplicated many times, coated onto microscopic gold and tungsten ?bullets? and literally blasted from a gene gun into the Petri dish containing the host cells. The scientist hopes upon hope that the entire package will be neatly inserted into the DNA of a host cell. Most miss their target. Some pass right through without delivering their payload leaving behind damaged DNA. Some cells end up with only portions of the package, some multiple copies. The fact that the DNA of the host organism can withstand such a violent barrage and survive relatively intact, says more of nature?s resilience than the precision of the scientist.

Michael Antoniou, molecular geneticist at King?s College London says of the biolistics process, ?It?s the imprecise way in which genes are combined and the unpredictability in how the foreign gene will behave in its new host that results in uncertainty. From a basic genetics perspective, GM possesses an unpredictable component that is far greater than the intended change.?

The biolistics process has direct relevance for Australian consumers. Monsanto?s GM canola being harvested in Victoria for the first time this year, has 40 ?rungs? of the parent plant DNA ?ladder? (base pairs) missing at one end of the new code insertion. At the other end there are 22 new rungs on the DNA ladder. It is not known where they came from (The EFSA Journal (2004) 29, 1-19).

It took geneticists more than 270 tries to clone ?Dolly? the sheep. But what of the 269 Dollys that didn?t make it? Many were deformed and disfigured, stillborn or unable to mature. Genetic engineering also creates many abnormal plants in the process of obtaining a few that end up being the progenitors of our food plants. Tobacco plants were genetically modified with the intention to increase their natural acid profile. Instead they produced a toxic compound not normally found in tobacco. A genetically modified potato unintentionally increased its starch content some 40 to 200 times.

The biotech industry erroneously believes that their foreign gene will behave exactly as it does in its natural setting. The working assumption is that genes determine characteristics in linear causal chains: one gene, gives one protein, gives one function.

This was the dominant model that held sway in the 1960s and is still a powerful tool for teaching the fundamentals of genetics, but like Einstein?s extension to Newtonian physics, our knowledge of genetics has evolved immeasurably.

Our current understanding tells us that genes behave in complex inter-related non-linear networks: causation is multi-dimensional and circular; and genes are subject to environmental feedback regulation. All these factors are excluded by the central reductionist dogma of the biotech industry, which prefers to adhere to the ?one gene, one protein, one function? model of yesteryear.

This narrow reductionist mindset allows GM companies to assert that their foreign gene will only produce the one intended protein and therefore will behave in the precise and controlled way they expect. Control and precision is also what biotech investors demand.

That the GM companies assume that their inserted foreign gene will only express the one intended protein is a manifestly risky assumption. In fact, the number of genes in nature that actually express a single protein can be counted on two hands. Most genes code for many proteins. In fact, the fruit-fly holds the record for the highest number of proteins expressed by a single gene - 38,016! It?s the gene?s ability to produce multiple proteins together with the location specific nature of gene expression that is believed to be responsible for the unexpected effects described in the experiments above. Disturbingly, the biotech industry and our food regulators do no testing for theses possible outcomes.

But there is a growing body of evidence that suggests that they should. Allergies have skyrocketed in the UK since the introduction of GM soy. In the US, a GM food supplement produced an epidemic of Eosinophilia Myalgia Syndrome (EMS) which killed 37 people and maimed thousands more. Mice fed GM soy had unexplained changes in testicular cells and rats fed GM corn showed significant changes in their blood cells, livers and kidneys.

All these GM products had been tested and approved for human consumption. Could the narrow reductionist lens with which the biotech industry views genetic engineering be resulting in unintended effects slipping through and onto our dinner plates?

Like the proverbial man looking for his car keys under the street lamp because there?s more light there, the biotech industry is using the dim candle of 1960?s genetics to assure us that GM food products in the 21st century are safe.

Applying an entirely random and uncontrolled gene insertion method, together with an outdated model of genetics to the profoundly fundamental question of food safety is literally taking a shot in the genetic dark with our health.

                                  PART 2

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SOURCE: Science Daily, USA



DATE:   01.12.2008

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ScienceDaily (Dec. 1, 2008) ? Hereditary information flows from parents to offspring not just through DNA but also through the millions of proteins and other molecules that cling to it. These modifications of DNA, known as ?epigenetic marks,? act both as a switch and a dial ? they can determine which genes should be turned on or off, and how much message an ?on? gene should produce.

One way in which epigenetic information is known to be passed from parent to offspring is through the pattern of chemical ?caps? added onto certain ?letters? of the DNA sequence, ensuring the sequence is ?silenced.? How these DNA capping patterns, which are inherited, are precisely set is not yet known. But in some cases, enzymes that add these caps are guided to DNA by small RNA molecules. These guides themselves do not carry hereditary information, but they do mark the spots where DNA is to be modified.

A team of scientists at Cold Spring Harbor Laboratory (CSHL) led by Professor Gregory J. Hannon, Ph.D., has now discovered that a class of small RNAs does carry epigenetic information and in fact passes on the trait of fertility from mother to offspring in fruit flies.

A new mechanism of inheritance

In a paper published in Science, the CSHL team reports that maternal small RNAs called Piwi-interacting RNAs (piRNAs) that are deposited into fruit fly embryos ?silence? DNA sequences that induce sterility, thus ensuring the fertility of the progeny. ?This is a whole new way in which heredity can be transmitted,? says Professor Hannon, who is a pioneer in small RNA research. ?With this finding we?ve effectively doubled the number of mechanisms by which epigenetic information is known to be inherited.?

The piRNAs are found only in cells of sex organs and partner up with proteins called Piwi to suppress the activity of mobile DNA sequences called transposons. Discovered half a century ago by CSHL scientist and Nobel laureate Barbara McClintock, Ph.D., transposons jump around the genome, inserting themselves into genes and causing mutations. Such genetic havoc is thought to underlie many diseases, including cancer.

A high rate of mutations also disturbs gametogenesis ? the process of creating viable sex cells ? and can result in sterility. Piwi proteins and piRNAs form something akin to an immune system in sex cells that guards against transposon-inflicted genome damage.

Solving the fruit fly fertility puzzle

The CSHL team wondered whether piRNAs were also the key to a long-standing conundrum about fertility in fruit flies. When lab-bred female flies are bred with male flies caught in the wild, their progeny are sterile or unable to produce offspring -- a phenomenon called hybrid dysgenesis. But the genetically identical offspring of wild-caught female flies and lab-bred males are fertile. The genetic difference between the lab-bred and wild flies is a single transposon, which is absent in lab strains.

In hybrid dysgenesis, the transmission of the transposon by a parent induces sterility in the offspring unless the offspring also inherits a factor that suppresses the transposon and maintains fertility. Since the phenomenon had only been seen when the transposon-transmitting parent was male, the suppressing factor was thought to be maternally transmitted. But it was never identified.

Hannon?s team has now found that the stockpile of maternally derived proteins, RNA, and nourishing raw material in developing fruit fly oocytes, or egg cells, also includes piRNAs. And these maternally deposited piRNAs prove to be essential for mounting a silencing response against transposons.

Inheritance via small RNAs

Hannon likens this protection to that afforded by the adaptive immune system which protects against pathogens like bacteria and viruses. ?We?ve evolved ways to transmit immunity from mother to child via the secretion of antibodies,? he says, referring to the proteins that can cross the placenta and protect the fetus or get passed on to an infant via breast-milk. ?We now have a way in which immunity (against sterility) is passed on from mother to child, in flies but possibly other organisms also, via small RNAs.?

In contrast to short-lived adaptive immunity, however, this small RNA-driven immunity has a long reach. The team?s experiments show that the effect on fertility doesn?t just impact the child alone, but also the next generation. Because the trait ? fertility ? is controlled or encoded in the RNA, ?you?re passing on a trait that?s essentially not only controlling an event that happens in the organism?s adulthood, but is also propagated to the progeny of that organism,? explains Hannon.

The impact of environment

The ability of the mother to transmit epigenetic information can be altered by the environment that she finds herself in. Other researchers have found that raising the temperature in which female flies are reared raises the proportion of fertile progeny.

To the CSHL team, this suggests that ?the experience of the mother translates into a dominant effect on the progeny.? The group?s data suggest that one way that the mother?s experience might get communicated to the child is through variations in the populations of small RNAs that get deposited in the oocytes.

Now that one trait has been discovered to be driven by maternally inherited piRNA, Hannon is eager to know if the spectrum of information that?s transmitted in this way can be broadened to cover other cellular processes. And of course, it also remains to be seen whether this mechanism of epigenetic inheritance is found in organisms besides fruit flies. ?Small RNAs are probably deposited in oocytes of every animal,? he hypothesizes.

Journal reference:

1. Brennecke et al. An Epigenetic Role for Maternally Inherited piRNAs in Transposon Silencing. Science, 2008; 322 (5906): 1387 DOI: 10.1126/science.1165171

Adapted from materials provided by Cold Spring Harbor Laboratory, via EurekAlert!, a service of AAAS.



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