Some of the earliest and most prominent uses of genetic modification technology in crops have related to disease management. The insertion of a Bacillus thuringiensis gene into crops such as corn resulted in protection against damage caused by certain insects, eliminating the need for pesticides against those particular pests is one example. Another example, the ability of crops to thrive despite the application of glyphosate, was brought about by modifying crops so that the pathway affected by the chemical to cause plant death is cycled more regularly, helping the crop to survive.
A recent review penned by Paul Vincelli in the journal Sustainability overviewed the possible targets of genetic modification to increase pest control, how and what types of modifications can increase immunity and the possible risks that must be addressed if engineering resistance is to be sustainable.
How can genetic engineering enhance disease management?
Engineering Pathogen-Associated Molecular Patterns (PAMPs) recognition
A common feature of the immune system of many eukaryotes is the ability to recognise particular patterns on pathogens (“PAMPs”). The patterns are conserved across species of pathogens and, once recognised by immune cells as they survey the cells present in their host they trigger an immune response.
Whilst all plants will have the ability to recognise a range of PAMPs, they wont recognise all of them. Therefore, if one species of plant has developed the ability to recognise a particular pathogen and defend against it, identifying the requisite gene and transplanting it into another plant that is struggling to defend against the same pathogen will quickly enable it to muster its own immune defence against it.
Resistance genes, or ‘R genes’, allow a plant to overcome effector molecules used by pathogens to increase their chances of successfully invading a host. In a never-ending arms race, a pathogen will develop an effector molecule to enhance susceptibility of the host to infection, while the host will in develop the ability to recognise the effector and induce the immune reaction again. In response, the pathogen may develop a new effector molecule, and the plant must again develop the ability to recognise the effector and respond when it is present.
The DNA encoding these new proteins developed by plants to detect new effectors are termed R genes, and the ongoing battle means that there are a multitude of R genes relating to a multitude of pathogens throughout the plant kingdom. Therefore, transferring R genes from a resistant plant to a susceptible plant will transfer resistance.
Transferring R genes can be done via conventional breeding, although some plants are easier and less time-consuming to cross-breed than others. Engineering the transfer of R genes will be quicker, more effective to use in difficult-to-cross crops and will enable more precise insertion of the genes, reducing the inheritance of unwanted genes along with the R genes.
Such a technique was used to transfer a gene from peppers which conferred resistance to bacterial leaf into tomato.
The obvious downside to conferring resistance this way is that the pathogen will again develop a new virulence method which will again need to be addressed, resulting in only a temporary resistance. However, helping crops quickly adapt to a new infection will help ensure short term yields while also allowing the engineering of specific resistance to specific pathogens as new effectors and R gene couples are discovered.
Giving Defence Responses a Boost
As well as increasing pathogen and effector recognition to allow immune responses to be initiated, increasing the size of those responses can also help combat specific pathogens.
An example provided in the paper is the use of a constitutive promoter from wheat to increase the expression of native immune gene which helped rice crops combat a number fungal pathogens including rice blast.
Changing DNA Sequences that Result in Increased Susceptibility
Some pathogens have developed the ability to exploit some required host protein to give itself a route of infection. The susceptibility genes encoding these proteins are problematic to deal with given the necessity of the gene product. However, modification to the gene, either natural or synthetic, which alters the protein enough to reduce their ability to be exploited by the pathogen but not so great as to render the protein useless in its required role, has been shown effective in increasing resistance.
Plants producing their own Antimicrobials
Like the Bt toxin producing corn crops that now protect themselves using the same chemistry used by conventional pesticides, crops producing their own antimicrobials provides a further potential basis for sustainable protection.
The discovery that double-stranded RNA results in the silencing of genes with a complementary sequence has led the ability insert genes into an organism coding for a double-stranded RNA which will silence a specific gene or, of use to us in plant immunity, will silence genes within a parasite to reduce or remove their pathogenicity. Such was the case with the papaya ringspot virus in Hawaii, which was overcome by engineering the papaya to produce a dsRNA complementary to a coat protein gene of the virus, removing a virulence factor relied upon by the virus and saving the industry.
Removing Host Virulence Factors
Similar to removing or modifying susceptibility genes to remove a target route of infection used by pathogens, removing or modifying host virulence factors such as a particular protein which allows strong binding of the pathogen is a potential method of reducing infection rates.
Detoxifying the toxins
Many pathogens produce toxins which will attack particular targets of plant cells to allow easier invasion. Being able to render the toxin ineffective will in turn reduce infection rates of many pathogens, and having the plant produce these detoxifying compounds is a possible means of sustainably reducing crop destruction from disease.
Using CRISPR/Cas 9
CRISPR and its ability to make target endonuclease activity to specific parts of a DNA sequence has seemingly limitless uses, including as a disease management tool. By targeting an endonuclease to DNA inserted into a plant, such as replicating DNA of Geminiviruses, will disrupt the replication and infection rates of numerous pathogens and holds the possibility of being an adaptable method of crop production.
Balancing Crop Protection and Resistance Selective Pressure
Although there are number of methods of increasing resistance through targeted means, evolution doesn’t allow us to simply pick a single method to eliminate a pathogen; resistance is an ongoing concern.
However, if the ability to use multiple methods of increased pest management is developed along with the ability to rotate what methods are used, we may manage to increase our crop protection and reduce the selective pressure we put on pests.
Stacking multiple genes into plants is a promising method of achieving this end and Plant Artificial Chromosomes may be the scaffold on which these methods of disease management can be simultaneously used in crops.
Concerns using Genetic Engineering
The usual concerns are raised and, although noted as risks that must be managed where there is a dearth of evidence confirming the size of the risk, those concerns are largely dismissed.
The health risks of genetically engineered crops are an oft-raised topic in public forums, but the science on the lack of risk is largely settled.
Flow of recombinant DNA into related plant species is discussed but is again largely dismissed save where further research should be conducted to quantify such risks. Given the context of such genes being already present in wild-type plants and therefore already available for gene flow, the lack of evidence of microorganisms being transformed by transgenes plus the ability to design synthetic gene components so as to be not usable by prokaryotic microorganisms, the use of genetic modification use has little chance of increasing the risk.
The control of genetic engineering by large companies and the promotion of monocultures are also raised as potential concerns related to using this technology in disease management programs. Again, the concerns raised fail to look at the current state of agriculture where large companies already hold the majority of patents for non-GMO technologies and where monoculture farming is a symptom of economic pressure unrelated to the use or disuse of genetic modification technology.
The review provides a great basis for further researching possible methods of sustainable disease management, pointing out the multiple paths that may be taken to research and develop protections against any particular plant pathogen.
The new technologies and any risks that come with them must be subject to rigorous risk analysis and the pros and cons weighed before implementation. Combining the use of multiple types of technology and managing the evolutionary pressure that could be caused if only one type of technology or only one target is used could create methods more sustainable and more targeted than those used today.