The evolutionary history and adaptive significance of UCP1-mediated thermogenesis in primates
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Abstract
Mitochondrial uncoupling protein 1 (UCP1), a key molecular component of brown adipose tissue (BAT), is pivotal to the process of non-shivering thermogenesis (NST). This dissertation provides a comprehensive investigation of UCP1 gene evolution in primates, spanning three distinct levels of analysis. I first examine the phylogenetic history of UCP1 in 41 primate taxa, in which I observed functional divergence between strepsirrhines and haplorhines with significant structural variation including clade-specific intronic insertions and duplications. This underscores the shifting patterns of directional selection on UCP1 in response to ecological pressures across primate lineages, potentially reflecting thermoregulatory challenges posed by varying body sizes and climatic habitats. I then explore population-level genetic variation in the UCP1 gene of wild savanna monkeys (Chlorocebus spp.), which ~450 kya expanded from equatorial to cold southernmost Africa. I identified several SNPs showing positive selective sweeps, for which derived allele frequencies were primarily associated with the strength of solar irradiance and winter precipitation; this was strongest in a population in the southern coastal belt of South Africa (isolated by the Drakensberg Mountains and the Nama Karoo). I suggest that reliance on sunbathing for warmth coupled with reduced solar irradiance potentially increases thermal stress in this coastal corridor, leading to selection on UCP1 due to increased reliance on NST. These SNPs are predominantly non-coding, suggesting the importance of UCP1 expression as a target of selection. Finally, I developed a novel method for converting archived wild savanna monkey fibroblast cell lines into chemically-induced brown adipose (ciBA). UCP1 expression via immunofluorescence staining, oil-red O stain confirming lipid formation, and mitochondrial activity shown by MitoTracker all indicate successful conversion into ciBA. The success of this method represents a critical step towards the validation of the functional significance of SNPs identified as having undergone recent selective sweeps in wild savanna monkeys. Overall, this research highlights the importance of NST as an adaptive trait in primates, while also underscoring the importance of convergent evolution in UCP1 expression as a vital adaptive response to colder environments in our own genus.
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2024