Isolation of small populations can reduce fitness through inbreeding depression and impede population growth. Outcrossing with only a few unrelated individuals can increase demographic and genetic viability substantially, but few studies have documented such genetic rescue in natural mammal populations. We investigate the effects of immigration in a subpopulation of the endangered Scandinavian arctic fox (), founded by six individuals and isolated for 9 years at an extremely small population size. Based on a long-term pedigree (105 litters, 543 individuals) combined with individual fitness traits, we found evidence for genetic rescue. Natural immigration and gene flow of three outbred males in 2010 resulted in a reduction in population average inbreeding coefficient (), from 0.14 to 0.08 within 5 years. Genetic rescue was further supported by 1.9 times higher juvenile survival and 1.3 times higher breeding success in immigrant first-generation offspring compared with inbred offspring. Five years after immigration, the population had more than doubled in size and allelic richness increased by 41%. This is one of few studies that has documented genetic rescue in a natural mammal population suffering from inbreeding depression and contributes to a growing body of data demonstrating the vital connection between genetics and individual fitness.

Genome-wide association studies provide good opportunities for studying the genetic basis of adaptive traits in wild populations. Yet, previous studies often failed to identify major effect genes. In this study, we used high-density single nucleotide polymorphism and individual fitness data from a wild non-model species. Using a whole-genome approach, we identified the MC1R gene as the sole causal gene underlying Arctic fox Vulpes lagopus fur colour. Further, we showed the adaptive importance of fur colour genotypes through measures of fitness that link ecological and evolutionary processes. We found a tendency for blue foxes that are heterozygous at the fur colour locus to have higher fitness than homozygous white foxes. The effect of genotype on fitness was independent of winter duration but varied with prey availability, with the strongest effect in years of increasing rodent populations. MC1R is located in a genomic region with high gene density, and we discuss the potential for indirect selection through linkage and pleiotropy. Our study shows that whole-genome analyses can be successfully applied to wild species and identify major effect genes underlying adaptive traits. Furthermore, we show how this approach can be used to identify knowledge gaps in our understanding of interactions between ecology and evolution.

The awareness of inbreeding as a potentially harmful process dates several centuries back in time, and occurred early in various religions, cultures, and societies. However, it was not until the 18th Century that the phenomenon was first investigated systematically through breeding experiments in domestic animals and plants. Investigations were followed by the establishment of the theoretical framework in the 19th Century by Darwin, Mendel and other pioneering evolutionary biologists. Throughout the development of this field, from breeding experiments and discoveries of the mechanism of inheritance, via heterozygosity‐fitness correlations, construction of pedigrees for natural populations, emergence of the conservation genetics field, to present‐day whole genome sequencing of extinct species, mammals have played a crucial role as model organisms and flagship species. In this review, we present a chronological overview of the theoretical development and empirical data on inbreeding in mammals, from the 18th Century to the present day. Furthermore, in relation to the current analytical capacity, we identify gaps in the knowledge and future challenges in the study of inbreeding and inbreeding depression in mammals.

Genetic rescue can facilitate the recovery of small and isolated populations suffering from inbreeding depression. Long-term effects are however complex and examples spanning over multiple generations under natural conditions are scarce. The aim of this study was to test for long-term effects of natural genetic rescue in a small population of Scandinavian Arctic foxes (Vulpes lagopus). By combining a genetically verified pedigree covering almost 20 years with a long-term dataset on individual fitness (n=837 individuals), we found no evidence for elevated fitness in immigrant F2 and F3 compared to native inbred foxes. Population inbreeding levels showed a fluctuating increasing trend and emergence of inbreeding within immigrant lineages shortly after immigration. Between 0-5 and 6-9 years post immigration, the average population size decreased by almost 22 % and the average proportion of immigrant ancestry rose from 14 % to 27 %. Y chromosome analysis revealed that two out of three native male lineages were lost from the gene pool, but all founders represented at the time of immigration were still contributing to the population at the end of the study period through female descendants. The results highlight the complexity of genetic rescue and suggest that beneficial effects can be brief. Continuous gene flow may be needed for small and threatened populations to recover and persist in a longer time perspective.

Reduced fitness through genetic drift and inbreeding is a major threat to small and isolated populations. Although previous studies have generally used genetically verified pedigrees to document effects of inbreeding and gene flow, these often fail to capture the whole inbreeding history of the species. By assembling a draft arctic fox (Vulpes lagopus) genome and resequencing complete genomes of 23 additional foxes born before and after a well‐documented immigration event in Scandinavia, we here look into the genomic consequences of inbreeding and genetic rescue. We found a difference in genome‐wide diversity, with 18% higher heterozygosity and 81% lower FROH in immigrant F1 compared to native individuals. However, more distant descendants of immigrants (F2, F3) did not show the same pattern. We also found that foxes with lower inbreeding had higher probability to survive their first year of life. Our results demonstrate the important link between genetic variation and fitness as well as the transient nature of genetic rescue. Moreover, our results have implications in conservation biology as they demonstrate that inbreeding depression can effectively be detected in the wild by a genomic approach.