PT  - JOURNAL ARTICLE
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
TI  - Inactivation of thermogenic UCP1 as a historical contingency in multiple placental mammal clades
AID  - 10.1101/086819
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 086819
4099  - http://biorxiv.org/content/early/2017/04/21/086819.short
4100  - http://biorxiv.org/content/early/2017/04/21/086819.full
AB  - 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 species tree constructed from a ∼51-kb sequence alignment 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 strong secondary reductions in metabolic intensity in xenarthrans and pangolins, or in six other lineages 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. 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 clades lacking functional UCP1, thus providing the first evidence for species selection related to the presence or absence of a single gene product.