Ancient, independent inactivations of the ucp1 gene, which encodes the uncoupling protein 1, or UCP1 (essential for thermogenesis in brown fat), were a major force driving the evolution of nearly half of all placental mammal orders, according to new research published in the journal Science Advances (biorXiv.org preprint).
Gaudry et al 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. Image credit: Mauricio Anton.
“Being ‘warm blooded’ has long been regarded as one of the most intriguing evolutionary outcomes of mammalian evolution,” said study first author Mike Gaudry, a student in the Department of Biological Sciences at the University of Manitoba.
“Brown fat is a key thermoregulatory tissue for neonates, including humans, and its evolution in early placental mammals is widely accepted to be the single most important factor that enabled the exploitation of cold environments by this group.”
“In contrast to this entrenched view, we demonstrate that this tissue is not necessarily linked to the evolution of cold tolerance in mammals, but instead show it was already non-functional in lineages that subsequently adapted to extremely cold environments (such as cetaceans, horses, woolly mammoths, Steller’s sea cows),” added senior author Dr. Kevin Campbell, also from the University of Manitoba.
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 possessing intact ucp1 loci are collapsed. Red boxes indicate ucp1 inactivation date ranges as determined by dN/dS analyses, while the dagger represents the complete deletion of this locus in the delphinid lineage. Pre-Oligocene temperatures are based upon a benthic foraminifera 18O isotope dataset assuming an ice-free ocean. Note that the majority of 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 (24.1x higher at 25 degrees Celsius). As only remnants of ucp1 were identified from representative Pilosa (Bradypus, Choleopus, Cyclopes), that moreover did not share common inactivating mutations with Cingulata, we were unable to reliably date its inactivation in this clade. Image credit: Gaudry et al, doi: 10.1126/sciadv.1602878.
A detailed examination of the fossil record also revealed that the inactivation of ucp1 was related to drastic reductions in metabolic intensity in two mammalian groups (sloths and pangolins), or with abrupt changes in body size in other lineages that lost the ability to generate heat via brown fat.
“Large bodied mammals are good at conserving heat, and so once this tissue was no longer required for thermoregulation, it presumably allowed more energy to be allocated to growth,” Dr. Campbell said.
“Increasing body size enabled the exploitation of new ecological niches and thus led to a rapid increase in species diversity in these groups.”
This initial evolutionary success was, however, not devoid of negative long-term fitness consequences as the research team demonstrated that loss of brown fat eventually lead to an elevated rate of extinction, and hence current low species diversity of lineages lacking a functional ucp1 gene.
“The re-evolution of small body size has presumably been prevented by competitive disadvantages versus species with brown fat, or has restricted medium-sized species lacking brown fat to tropical/subtropical environments,” Dr. Campbell explained.
“Thus, the number of species in these groups has dwindled precipitously over the past few million years, and, unfortunately they may be further impacted by ongoing climate change.”
“In short, these findings uncover the molecular basis for a slow metabolism in some mammalian lineages, and for the ecological niche expansion, diversification, and subsequent extinction patterns evident in the fossil record of a number of large-bodied groups that have puzzled researchers for the past 50 years,” Gaudry said.
In addition to thermoregulation, brown fat has been implicated in the regulation of food intake, energy balance, and even longevity.
As such, it has fuelled intensive research to develop therapeutic interventions for cancer cachexia, obesity, diabetes, and other metabolic disorders, making it one of the hottest topics in medical biology.
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Michael J. Gaudry et al. 2017. Inactivation of thermogenic UCP1 as a historical contingency in multiple placental mammal clades. Science Advances 3 (7): e1602878; doi: 10.1126/sciadv.1602878
This article is based on text provided by the University of Manitoba.
