Molecular evolution of UCP1 and the evolutionary history of mammalian non-shivering thermogenesis

David A Hughes,Mark Stoneking,Martin Jastroch,Martin Klingenspor

doi:10.1186/1471-2148-9-4

Abstract

BackgroundUncoupling protein 1 (UCP1) is a mitochondrial anion carrier, expressed in brown adipose tissue (BAT) of Eutherians. UCP1 is responsible for uncoupling mitochondrial proton transport from the production of ATP, thereby dissipating heat; it is essential for non-shivering thermogenesis (NST) in mammalian BAT. UCP1 orthologs have been identified in non-Eutherian mammals, fish and amphibians. Yet, UCP1 has a unique function in Eutherians in that it is necessary in the production of heat (NST). As such, this study aims to determine the evolutionary mode of UCP1 in Eutherians, where there is clear evidence of UCP1-dependent NST in BAT.ResultsModels of adaptive evolution through phylogenetic analysis of amino acid sequences by maximum likelihood were implemented to determine the mode of UCP1 protein evolution in Eutherians. An increase in the rate of amino acid substitutions on the branch leading to Eutherians is observed, but is best explained by relaxed constraints, not positive selection. Further, evidence for branch and site heterogeneity in selection pressures, as well as divergent selection pressures between UCP1 and its paralogs (UCP2-3) is observed.ConclusionWe propose that the unique thermogenic function of UCP1 in Eutherians may be best explained by neutral processes. Along with other evidence, this suggests that the primary biochemical properties of UCP1 may not differ between Eutherians and non-Eutherians.

Highlights

Uncoupling protein 1 (UCP1) is a mitochondrial anion carrier, expressed in brown adipose tissue (BAT) of Eutherians
In Eutherians, UCP1 is the only gene known to be exclusively expressed in brown adipose tissue (BAT), accounting for up to 5% of the total mitochondrial protein in BAT [3]; UCP1 provides Eutherians, small mammals, hibernators and newborns, with a unique mechanism of non-shivering thermogenesis (NST) [4]
Available UCP1, UCP2, and UCP3 sequences were retrieved from 39 species ranging from teleost fishes to mammals (Additional file 1)

Summary

Introduction

Uncoupling protein 1 (UCP1) is a mitochondrial anion carrier, expressed in brown adipose tissue (BAT) of Eutherians. BMC Evolutionary Biology 2009, 9:4 http://www.biomedcentral.com/1471-2148/9/4 membrane of brown adipocyte mitochondria This increased proton conductance uncouples mitochondrial respiration from ATP synthesis and thereby dissipates the proton motive force as heat [6,7,8,9]. Repeating the MC model but setting the Eutherian UCP1 lineage (E) (i.e. just branch E, not the clade) as the foreground branch, an ω of 0.87 is estimated for divergent sites, while background lineages have an ω of 0.18, where p2 = 0.390 (2Δᐍ = 1119, p < 0.001; identical ᐍ to Clade E (Table 2)) These analyses indicate that the UCP1 phylogeny exhibits large divergent selection pressures, which may principally involve the Eutherian UCP1 lineage, consistent with the possible acquisition of the new function of UCP1 through neutrally evolving, relaxed constraints

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Conclusion