Genome engineering technologies
How do scientists change DNA?
Genome engineering technologies are powerful tools used by researchers around the world. From making allergen-free food to eliminating disease, the usefulness of changing the genomes of animals and plants seems almost boundless.
There are a number of methods that scientists can use to change the genome of an organism. But how do they actually work?
First, some definitions:
Genome - the complete set of genetic instructions in an organism, which contains all of the information needed for it to grow, develop and function.
Gene - a section of the genome that contains the instructions to make a molecule, usually a protein. The products of genes determine the characteristics, or traits, of an organism such as eye or hair colour.
DNA - the molecule that contains an organism’s genetic code. DNA is made up of four chemical bases – A, T, G, and C – which form the genetic alphabet.
The oldest form of genome engineering is selective breeding, which has been used since the dawn of agriculture to create the crops and livestock that provide us with food today. Rice for example, has been cultivated and selectively bred for over 7000 years. Farmers choose individual plants or animals that have useful qualities or traits and use them for breeding. If the traits can be inherited, their offspring will have new combinations of these traits.
Inherited traits are determined by the genes that individual plants and animals carry, and due to natural mutations in the DNA sequence, these genes change over time. These same mutations create different versions of genes in a population. As a result of selective breeding, useful or desirable versions of genes become more common and other less useful versions become less common, or are even eliminated, creating crops and livestock that produce more and better quality food.
Selective breeding was in use for thousands of years before the genetic mechanisms of inheritance were understood. Today we can use this knowledge, and tools that allow us to analyse DNA, to make the process faster and more precise. With modern genotyping techniques we can quickly find individuals that have or lack a specific gene of interest, and breed them with other individuals that we can identify in the same way. This means that we can make significant and targeted changes in a small number of generations. At The Roslin Institute we have used selective breeding, informed by genome sequencing and analysis, to breed salmon that are resistant to a deadly virus called IPN.
Selective breeding is simple, cost effective and can quickly improve animal and plant genomes. However, it can only work with traits and versions of genes that already exist in the population.
As with any genetic engineering tool, selective breeding must be used responsibly. Selective breeding for one set of traits can lead to unintended consequences in other areas, such as breathing difficulties in flat-faced dogs and an inability of some heavily muscled cattle breeds to give birth naturally. It is our responsibility to make sure that what we select for is not detrimental to the animal whilst providing a benefit to the consumer.
Genetic Manipulation and Transgenesis
In the 1970s, the discovery of tools that could directly manipulate DNA began the development of a comprehensive genetic engineering toolbox that allow genetic modification (GM) of plants and animals. Using these tools, DNA in an organism can be changed, removed or added to, producing changes in its traits which can complement selective breeding. One technique, known as transgenesis, involves taking useful genes from one organism and adding them to the genome of another, creating a genetically modified organism or GMO.
The many applications of transgenesis include using genetically modified microorganisms to produce proteins such as insulin to treat diabetes, and rennet which is used in cheese making. Transgenesis has also produced chickens unable to transmit bird flu, pest-resistant cotton and maize, and is commonly used in scientific research to study how genes and their products work within cells and organisms.
Genome editing is the newest technique and can precisely modify the DNA inside a cell. There are several types of genome editing tools; most of them are designed to cut DNA at specific target sequences. Once cut, DNA bases can be changed, removed or added to alter the genome in a precise manner. This results in predictable changes to the traits of the organism.
Genome editing can be used to make changes to the DNA of any organism, without having to wait for a random mutation to occur naturally. It gives scientists an increased level of control in what changes occur in the genome, providing a more targeted approach. Genome editing can make very small changes such as changing a single base of the DNA code, or larger changes such as removing a section of a gene.
Genome editing has been used for a wide range of application from new immune therapies to treat cancer, to producing dairy cattle that don’t grow horns, eliminating the need for horn removal. Scientists at The Roslin Institute have also used it to create pigs that are resistant to the deadly PRRS virus.
When to use these tools
The concept of genome engineering makes some people uncomfortable. At The Roslin Institute, our mission is to improve animal welfare, promote global food security, and reduce the impact of animal disease on farmed animals and humans. We are using these genetic tools in order to meet those aims, often though basic laboratory research in cell and tissue models, but also in whole animals. At present, GM animals are not permitted to enter the food chain. If we are to implement some of these strategies on the farm to improve the ecological footprint or welfare of our animals, further discussion with the public, stakeholders, and policy makers is needed.
If you would like to learn more about our objectives and decision making process, please take a look at our mission statement. We are also featuring research stories which show how we are using these genome engineering tools, and their impact.
Special thanks to Sonal Katyal MSc for Video and animation.