Genomic effects of inbreeding on Scandinavian wolves

For many years, researchers at Uppsala University have been exploring the genetic origins of the Scandinavian grey wolf population, which was founded by only three immigrating wolves. In their new study the scientists show that, after five generations of inbreeding, between 10 and 25 per cent of the original genetic variation has been eliminated.

The fact that inbreeding is harmful and may directly cause extinction of endangered species is well known. But no research has ever been done to find out exactly how much genetic variation is lost because of closely related individuals mating with one another, or how it occurs.

The Scandinavian wolf population was founded by three individual wolves immigrating from Finland in the early 1980s. Geneticists at the University’s Evolutionary Biology Centre have now, by following trends of the population, been able to see the genomic effects of inbreeding over several generations.

Like us humans, all wolves have two slightly different versions or “copies” of every single chromosome in their DNA. The three founders of the wolf population thus contributed a total of six of every chromosome. The minor differences among these versions made up the baseline genetic variation in the population.

“We determined the DNA sequence for each of the six ‘starting chromosomes’ and for all the chromosomes of about a hundred wolves born from the 1980s to the present. We were then able to follow how far the starting chromosomes ‘survived’ from one generation to the next. What happened was that parts of them gradually disappeared from the population, so that the variation was lost,” says Hans Ellegren, Professor of Evolutionary Biology at Uppsala University.

The study is unique in that the researchers managed to follow the inheritance of so-called haplotypes. A haplotype is the linear combination of genetic variants along a chromosome. Current technology cannot distinguish the two haplotypes when one determines the DNA sequence of a biological sample. What the researchers now did could be seen as doing a jigsaw puzzle. By following the inheritance of chromosomes, they could deduce the composition of haplotypes.

When genetic variation is lost in a population, there is a deterioration in the individuals’ ability to face change and challenges. Some of the variants eliminated may have been important for the wolves’ further adaptive capacity. Others may have played a vital role as protection against genetic predisposition to disease.

In a population started by so few individuals, a genetic variant can easily disappear altogether. It cannot then be re-created without an influx of individuals.

“We found that, after five generations of inbreeding, 10 to 25 per cent of the genetic variation that the three founders brought with them had been lost. In total, no fewer than 160,000 genetic variants disappeared — a surprisingly large number,” Ellegren says.

An additional problem for the Scandinavian wolf population is that the three founders also turned out not to have been entirely unrelated to one another. Together, as mentioned above, they had contributed six chromosome “copies” but, in practice, these represented only about four different versions on average, since the animals were already related.

The results from the study have a general bearing on the implications of inbreeding in animal species.

“One key conclusion is that inbred populations need a supply of new genetic material, preferably with a provenance as different as possible from that of the population itself. To assess the extent of loss of genetic variation, you also need to be aware of how much variation there actually was from the start,” Ellegren says.

A few immigrating wolves have contributed new genetic variants to the population in recent years. Still, however, the extent of inbreeding is so large that also these variants run the risk of getting lost.

The study was conducted in collaboration with researchers at Grimsö Wildlife Research Station and from Norway.