Mutation in non-coding DNA makes pigs more muscular and less fat

Researchers at Uppsala University and the Swedish University for Agricultural Sciences (SLU) report in the latest issue of Nature that they have identified a regulatory mutation in a gene for a known growth factor that makes pigs more muscular and less fat than wild boars.

Most characteristics, such as common diseases like diabetes, have a multifactorial background, which means that they are influenced by many different genes and environmental factors. Even though we know the entire DNA sequence for the genetic make-up of human beings, we still know very little about hereditary factors that impact multifactorial properties and diseases. It has proven to be considerably more difficult to perform genetic studies of these compared with simple hereditary disease that are caused by mutations in a single gene.

Now researchers at Uppsala University and SLU, in collaboration with scientists at the University of Liege and the Roslin Institute, have shown that our domesticated animals can be a goldmine when it comes to disentangling the complex connections between genes and various characteristics. This is a result of the hybridization pursued by humans for thousands of years with the aim of adapting domesticated animals for the production of food and other use. This selection has led to the enrichment of those mutations that yield beneficial characteristics.

For the last 50 years breeders have been trying to create pigs that grow more rapidly and produce lean meat. More than ten years ago scientists at Uppsala, under the direction of Leif Andersson, crossed wild boars with domesticated pigs with the aim of attaining basic knowledge about what genetic changes have been brought about by breeding.

The research team has now identified a mutation in a single base pair that explains a considerable part of the difference in the development of muscle and the accumulation of fat between the wild boar and the pig. The mutation is located in the gene that codes for the protein Insulin-like Growth Factor 2 (IGF2), which is a known growth factor. What makes this especially exciting is that this mutation is regulatory, meaning that it does not influence the structure of the IGF2 protein, but rather the amount of IGF2 protein that is produced in the muscle. The effect of the mutation is moreover tissue-specific, since it does not affect how much IGF2 is produced in the liver or before birth.

The study shows that it is just as important to study the regulation of genes as their structure in order to understand hereditary differences in various characteristics in humans and other organisms. Even though this mutation was completely unknown until very recently, much use has been made of it in the breeding of pigs.

The research team demonstrates that this mutation has increased dramatically in several different races of domesticated pigs used for meat production. In certain races it has practically replaced the variant found in wild boars.

The scientists also show that the region of non-coding DNA that is mutated (a portion of intron number 3 in IGF2) is identical in pigs and humans. The some 100 persons who have been examined have the same DNA sequence as the wild boar in this position. This discovery is of great significance in the practical breeding of pigs and, in the long run, can lead to new forms of treatment for muscle weakness in humans. The study provides new basic knowledge about a mechanism that regulates muscle mass in mammals.

Article in Nature: Van Laere, A.-S., Nguyen, M., Braunschveig, M., Nezer, C., Collette, C., Moreau, L., Archibald, A.L., Haley, C.S., Buys, N., Tally, M., Andersson, G., Georges, M. & Andersson, L. “A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig” Nature 425, 832-836