Inactivation of thermogenic UCP1 as a historical contingency in multiple placental mammal clades

TY - JOUR

T1 - Inactivation of thermogenic UCP1 as a historical contingency in multiple placental mammal clades

AU - Gaudry, Michael J.

AU - Jastroch, Martin

AU - Treberg, Jason R.

AU - Hofreiter, Michael

AU - Paijmans, Johanna L.A.

AU - Starrett, James

AU - Wales, Nathan

AU - Signore, Anthony V.

AU - Springer, Mark S.

AU - Campbell, Kevin L.

N1 - © 2017, The Authors

PY - 2017/7/12

Y1 - 2017/7/12

N2 - 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 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 8 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 (for example, 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.

AB - 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 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 8 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 (for example, 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.

UR - http://www.scopus.com/inward/record.url?scp=85029703887&partnerID=8YFLogxK

U2 - 10.1126/sciadv.1602878

DO - 10.1126/sciadv.1602878

M3 - Article

AN - SCOPUS:85029703887

SN - 2375-2548

VL - 3

JO - Science Advances

JF - Science Advances

IS - 7

M1 - e1602878

ER -