TY - JOUR T1 - Inactivation of thermogenic UCP1 as a historical contingency in multiple placental mammal clades JF - bioRxiv DO - 10.1101/086819 SP - 086819 AU - Michael J. Gaudry AU - Martin Jastroch AU - Jason R. Treberg AU - Michael Hofreiter AU - Johanna L.A. Paijmans AU - James Starrett AU - Nathan Wales AU - Anthony V. Signore AU - Mark S. Springer AU - Kevin L. Campbell Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/11/09/086819.abstract N2 - Mitochondrial uncoupling protein 1 (UCP1) is essential for non-shivering thermogenesis in brown adipose tissue and is widely accepted to have played a key thermoregulatory role in small-bodied and neonatal placental mammals that enabled the exploitation of cold environments. Here we map ucp1 sequences from 133 mammals onto a 51-kb species tree and show that inactivating mutations have occurred in at least eight of the 18 traditional placental orders, thereby challenging the physiological importance of UCP1 across Placentalia. Selection and timetree analyses further reveal that ucp1 inactivations temporally correspond with secondary reductions in metabolic intensity in xenarthrans and pangolins, or coincided with a ∼30 million year episode of global cooling in the Paleogene that promoted sharp increases in body mass and cladogenesis evident in the fossil record of other lineages lacking a functional UCP1. Our findings also demonstrate that members of various lineages (e.g., cetaceans, horses, woolly mammoths, Steller’s sea cows) evolved extreme cold hardiness in the absence of UCP1-mediated thermogenesis. Finally, we identify ucp1 inactivation as a historical contingency that is linked to the current low species diversity of UCP1-less clades, thus providing the first evidence of species selection related to the presence or absence of a single gene product. ER -