He gets to know animals through their genes

Hanging on the wall of Leif Andersson’s office at the Department of Medical Biochemistry and Microbiology is a colourful picture of pigs. It was created by a student and depicts a study in which Leif Andersson crossed domestic pigs with wild boars to investigate what genetic changes occur when a wild species is transformed into a domestic animal.

Questions about how different genes and gene variants control traits are the very foundation of his research.

“I started that work in the late 1980s. That was when genetic engineering began to be used to study human diseases linked to genes, but I was a pioneer in using it to understand the genetic changes that have occurred in domestic animals,” says Leif Andersson.

Becoming a researcher was not something that had ever crossed his mind when he was young. But by chance, he got a job as a research assistant at the Swedish University of Agricultural Sciences (SLU).

“I realised that we could learn a great deal about genetics and the genetics of traits from domestic animals. This is because we humans have changed our plants and animals over the last ten thousand years to suit our needs. So, what I realised during those years was that domestic animals are a model for understanding evolutionary changes, because we can see so clearly when new traits appear,” explains Leif Andersson.

Found genes for horse colour

He began conducting genome mapping to find out how breeding has affected domestic animals at the molecular level.

“My thesis focused primarily on genetic mapping in horses. We mapped genes for traits such as coat colour: chestnut and what is known as roan. So, we conducted comparative genomics very early on and compared the genetic map for horses with the genetic map for mice, for example, and were able to predict some of the colour variations in horses that corresponded to colour variations in mice. The genome is fairly conserved between different species,” explains Leif Andersson.

After defending his thesis in 1983, he started his own research group and was placed at the Wallenberg Laboratory at Uppsala University. This turned out to be an extremely important period in his career. There were many other promising young researchers who, like him, wanted to explore the possibilities and push the boundaries of the new genetic engineering technology. Many of them would go on to become world leaders in their fields, including future Nobel Prize winner Svante Pääbo, who was a doctoral student at the time.

“It was a very creative environment that made you feel like anything was possible,” recalls Leif Andersson.

Wandering between different species and questions

He has retained that attitude and eagerly thrown himself into new projects. Over the years, he has mapped the genes responsible for horse gaits, feather colour in chickens, the mechanisms that regulate muscle mass in pigs, and how rabbits became tame and which genes control their ability to jump.

“Some researchers may be very focused on one thing, working with one species, while I explored in what ways this technology could be used to discover something new and exciting. So, I have wandered between different species and questions,” he says.

In recent years, Leif Andersson has devoted much of his time to studying Atlantic and Baltic herring, which belong to the same species and simply differ by location of origin. He has been interested in these fish ever since he studied biology at Stockholm University in the late 1970s, when they were the focus of his degree project. At that time, it was not possible to determine how Atlantic and Baltic herring differed genetically, so he did not pursue his fish studies any further. But he never gave up on solving the puzzle.

Returned to herring

By 2010, technological developments had advanced to the point where it was possible to sequence the entire genome of any species. So, he felt it was time to give it another try.

“When we began these studies, we had the impression that all Atlantic herring belonged to the same population. But what we have now learned is that they are divided into many smaller populations, subpopulations, each with its own specific adaptation. The most critical factor for an Atlantic herring population is how successful spawning is. You could say that different stocks of Atlantic and Baltic herring are determined by their spawning grounds in terms of time and location. On our coast, we have populations that spawn in the spring and those that spawn in the autumn. But there are also those that spawn in early spring, late spring and around midsummer, in early July. And they are genetically different,” explains Leif Andersson.

Contribution to fisheries management

In recent years, there has been much talk about the sharp decline in Baltic herring stocks due to overfishing. Leif Andersson is keen to find out how different stocks have been affected. His research has already been helpful to fisheries management.

“We have developed a method, which we call snip-chip, in which thousands of DNA markers are examined. It is now being used to map the different stocks. The samples are collected on ships and the data is then analysed, enabling us to monitor how different stocks are developing. Our research has had a direct application in how stock estimates are made,” says Leif Andersson.

In the field of domestic animal breeding, he highlights a discovery he and his research team made in pigs as one of the most valuable. They found a mutation that caused the pigs to have very high levels of glycogen in their muscles.

“Glycogen binds water. When the meat was cooked, the water disappeared. This resulted in the Christmas ham shrinking in size and being of poor quality. It was a huge problem. But we discovered a specific gene that was mutated. The DNA test was used to eliminate this problem worldwide. It was worth perhaps a billion dollars a year to the industry because it removed a significant quality problem. It was our research that made it possible to eliminate the problem,” says Leif Andersson.

New knowledge about mammalian muscles

The discovery led to new fundamental knowledge about the energy metabolism of mammalian muscles and also provided a new approach to treating diabetes in humans.

“Generally speaking, you could say that the research I have conducted over the years on both domestic animals and Atlantic herring has not only provided new fundamental knowledge about the function of genes and their significance, but has also led to practical applications. This has been important in domestic animal breeding and now in the monitoring of Atlantic herring stocks,” he says.

Åsa Malmberg