​Comparative genomics of Balto, a famous historic dog, captures lost diversity of 1920s sled dogs

Abstract

We reconstruct the phenotype of Balto, the heroic sled dog renowned for transporting diphtheria antitoxin to Nome, Alaska, in 1925, using evolutionary constraint estimates from the Zoonomia alignment of 240 mammals and 682 genomes from dogs and wolves of the 21st century. Balto shares just part of his diverse ancestry with the eponymous Siberian husky breed. Balto's genotype predicts a combination of coat features atypical for modern sled dog breeds, and a slightly smaller stature. He had enhanced starch digestion compared with Greenland sled dogs and a compendium of derived homozygous coding variants at constrained positions in genes connected to bone and skin development. We propose that Balto's population of origin, which was less inbred and genetically healthier than that of modern breeds, was adapted to the extreme environment of 1920s Alaska.

Figure 1.. Balto clusters most closely with Alaskan sled dogs, but had high genetic diversity and a lower burden of potentially damaging variants.

(A) Neighbor-joining tree clusters Balto (★) most closely with the outbred, working population of Alaskan sled dogs, and a part of a clade of sled dog populations. (B) Similarly, principal component analysis puts Balto near, but not in, a cluster of Alaskan sled dogs. (C) Unsupervised admixture analysis of Balto alongside the Alaskan sled dogs and other dogs and canids (K= 116 putative populations and N= 2166 individuals) infers substantial ancestral similarity to Siberian huskies, Greenland sled dogs, and outbred dogs from Asia (table S2). The remainder of his ancestry (8%) matches poorly (<5%) to any other clusters. Balto and working sled dogs (D) had lower levels of inbreeding, and (E) carried fewer constrained (p_wilcox=0.0019) and missense (p_wilcox= 0.0023) rare variants than modern dog breeds (table S10).

Figure 2.. Genomic recreation of Balto’s physical appearance.

(A) Prediction of Balto’s coat features based on his genome sequence with details on each trait and genotype in blue boxes. (B) A photo of Balto with musher Gunnar Kaasen. From the photo and his taxidermied remains, Balto was a black dog with dark eyes and some white patches on his chest and legs. He had a double-layered coat, and stood just under knee-high relative to Kaasen. Photo credit: Cleveland Museum of Natural History. (C) Using a random forest model based on 1,730 dogs and 2,797 height-associated genetic variants (12), we predicted that Balto would stand around 55 cm tall (value: 2.3) at his withers, close to the average height for the Siberian husky breed. Circles show dogs from other breeds. (D) Gene set enrichment testing of genes with common and constrained missense variants in 57 different dog populations shows a significant enrichment (p_FDR=0.013) in the GO Tissue Development pathway only for Balto’s population.