Survival and divergence in a small group: The extraordinary genomic history of the endangered Apennine brown bear stragglers | Andrea Benazzo, Emiliano Trucchi, James A. Cahill, Pierpaolo Maisano Delser, Stefano Mona, Matteo Fumagalli, View ORCID ProfileLynsey Bunnefeld, Luca Cornetti, Silvia Ghirotto, Matteo Girardi, Lino Ometto, Alex Panziera, Omar Rota-Stabelli, Enrico Zanetti, Alexandros Karamanlidis, Claudio Groff, Ladislav Paule, Leonardo Gentile, View ORCID ProfileCarles Vilà, Saverio Vicario, Luigi Boitani, View ORCID ProfileLudovic Orlando, Silvia Fuselli, Cristiano Vernesi, View ORCID ProfileBeth Shapiro, View ORCID ProfilePaolo Ciucci, and Giorgio Bertorelle

About 100 km east of Rome, in the central Apennine Mountains, a critically endangered population of ∼50 brown bears live in complete isolation. Mating outside this population is prevented by several 100 km of bear-free territories. We exploited this natural experiment to better understand the gene and genomic consequences of surviving at extremely small population size. We found that brown bear populations in Europe lost connectivity since Neolithic times, when farming communities expanded and forest burning was used for land clearance. In central Italy, this resulted in a 40-fold population decline. The overall genomic impact of this decline included the complete loss of variation in the mitochondrial genome and along long stretches of the nuclear genome. Several private and deleterious amino acid changes were fixed by random drift; predicted effects include energy deficit, muscle weakness, anomalies in cranial and skeletal development, and reduced aggressiveness. Despite this extreme loss of diversity, Apennine bear genomes show nonrandom peaks of high variation, possibly maintained by balancing selection, at genomic regions significantly enriched for genes associated with immune and olfactory systems. Challenging the paradigm of increased extinction risk in small populations, we suggest that random fixation of deleterious alleles (i) can be an important driver of divergence in isolation, (ii) can be tolerated when balancing selection prevents random loss of variation at important genes, and (iii) is followed by or results directly in favorable behavioral changes.

Financial support for the collection of the samples was provided by Vodafone Greece and the Vodafone Group Foundation. Fondo Ateneo Ricerca (FAR) grants from the University of Ferrara supported the study. P.M.D. was funded by Agence Nationale de la Recherche Demochips Grant ANR-12-BSV7-0012.