Fig. 3. UCP1 inactivation across a time-calibrated placental mammal phylogeny.

Functional ucp1 branches are denoted in black, pseudogenic branches in red, and mixed branches (where ucp1 inactivation occurred) in blue. Clades having intact ucp1 loci are collapsed. Red boxes indicate ucp1 inactivation date ranges as determined by d_N/d_S analyses (see table S3), whereas the dagger represents the complete deletion of this locus in the delphinid lineage (see Fig. 2B). Pre-Oligocene temperatures are based on a benthic foraminifera δ¹⁸O isotope data set assuming an ice-free ocean (165–167). Note that most inactivations correspond to a period of intense global cooling (gray shading) following the Paleocene-Eocene thermal maximum (PETM). Within this window, ucp1 was inactivated earlier in the two aquatic species, consistent with the much higher thermal conductivity of water relative to air (~24.1× higher at 25°C). Because only remnants of ucp1 were identified from representative Pilosa (Bradypus, Choleopus, and Cyclopes), the presented inactivation range should be interpreted with caution, and it is possible that ucp1 pseudogenization preceded its divergence from Cingulata. Artwork by C. Buell.