The uncoupling protein 1 gene (UCP1) is disrupted in the pig lineage: a genetic explanation for poor thermoregulation in piglets

Abstract

Piglets appear to lack brown adipose tissue, a specific type of fat that is essential for nonshivering thermogenesis in mammals, and they rely on shivering as the main mechanism for thermoregulation. Here we provide a genetic explanation for the poor thermoregulation in pigs as we demonstrate that the gene for uncoupling protein 1 (UCP1) was disrupted in the pig lineage. UCP1 is exclusively expressed in brown adipose tissue and plays a crucial role for thermogenesis by uncoupling oxidative phosphorylation. We used long-range PCR and genome walking to determine the complete genome sequence of pig UCP1. An alignment with human UCP1 revealed that exons 3 to 5 were eliminated by a deletion in the pig sequence. The presence of this deletion was confirmed in all tested domestic pigs, as well as in European wild boars, Bornean bearded pigs, wart hogs, and red river hogs. Three additional disrupting mutations were detected in the remaining exons. Furthermore, the rate of nonsynonymous substitutions was clearly elevated in the pig sequence compared with the corresponding sequences in humans, cattle, and mice, and we used this increased rate to estimate that UCP1 was disrupted about 20 million years ago.

Figure 1. Characterization of the UCP1 Locus in Pigs

(A) Wild boar sow with striped piglets in their nest. (B) Dotpath alignments of genomic UCP1 sequences from pigs, humans, and cattle. The approximate positions of the six exons in human UCP1 are indicated. Gap1 and Gap2 indicate two gaps in the alignment between the pig and human sequences. (C) Rate of nonsynonymous and synonymous substitutions in pairwise comparisons of UCP1 sequences from humans, mice, cattle, and pigs. The data are based on sequences from exon 1, 2, and 6. B, Bos taurus; H, Homo sapiens; M, Mus musculus; and S, Sus scrofa. (Photo: Anneli Andersson, Linköping University, Sweden)