biostudies-literatureUnknown3(7)Gaudry MJMitochondrial uncoupling protein 1 (UCP1) is essential for nonshivering 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. We map <i>ucp1</i> 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 8 of the 18 traditional placental orders, thereby challenging the physiological importance of UCP1 across Placentalia. Selection and timetree analyses further reveal that <i>ucp1</i> inactivations temporally correspond with strong secondary reductions in metabolic intensity in xenarthrans and pangolins, or in six other lineages coincided with a ~30 Science advancese1602878https://www.ebi.ac.uk/biostudies/studies/S-EPMC5507634biostudies-literatureInactivation of thermogenic UCP1 as a historical contingency in multiple placental mammal clades.PMC5507634Jastroch MTreberg JRGaudry MJSignore AVStarrett JCampbell KLWales NPaijmans JLASpringer MSHofreiter MfalseInactivation of thermogenic UCP1 as a historical contingency in multiple placental mammal clades.Mitochondrial uncoupling protein 1 (UCP1) is essential for nonshivering 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. We map <i>ucp1</i> 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 8 of the 18 traditional placental orders, thereby challenging the physiological importance of UCP1 across Placentalia. Selection and timetree analyses further reveal that <i>ucp1</i> inactivations temporally correspond with strong secondary reductions in metabolic intensity in xenarthrans and pangolins, or in six other lineages coincided with a ~30 2017-01-01T00:00:00Z2017 Jul2026-05-05T11:14:34.572Z2019-03-26T23:25:50ZS-EPMC55076342870698910.1126/sciadv.1602878