# The Evaluation of Significance of Uncoupling Protein Genes UCP1, UCP2, UCP3, UCP4, UCP5, and UCP6 in Human Adaptation to Cold Climates

## TL;DR

This study explores how variations in uncoupling protein genes help the Yakut people adapt to extreme cold, focusing on UCP1 and UCP3.

## Contribution

The study identifies specific SNP variants in UCP1 and UCP3 linked to cold adaptation in the Yakut population.

## Key findings

- Polymorphic variants rs3811787 (UCP1) and rs1800849 (UCP3) showed the highest scores for cold adaptation traits.
- UCP1 and UCP3 are suggested to play roles in non-shivering and shivering thermogenesis for cold adaptation.
- Variants of UCP genes were associated with thyroid hormone levels and body surface area in cold climates.

## Abstract

In this study, we present an analysis of SNP variants of six uncoupling protein genes in the Yakut population living in the coldest region of Siberia (minimum temperature −71.2 °C) in the context of human adaptation to cold climates. Uncoupling protein 1 (UCP1) is a transmembrane protein that may play an important role in thermogenesis; the functional role of other UCPs is clearly not known. Based on our results, we suggest that uncoupling proteins UCP1 and UCP3 are involved in human adaptation to a cold climate by increasing heat production. Thus, understanding the molecular details of the functional role of the UCPs could pave the way for the development of novel therapeutics to curb metabolic diseases such as obesity and diabetes.

Six isoforms of uncoupling proteins (UCPs) exist, spanning from UCP1 to UCP6. A precise physiological function has only been established for UCP1, which is involved in non-shivering thermogenesis, but the functions of other UCPs are still not fully defined. Therefore, the purpose of the present study is to search for indications of the involvement of nine polymorphic variants of UCP1-6 genes in human adaptation to cold climates using four criteria: (1) the presence of associations of polymorphic variants of UCP genes with levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine; (2) the presence of associations of polymorphic variants of UCP genes with changes in thyroid homeostasis (SPINA); (3) the presence of associations of polymorphic variants of UCP genes with body surface area; (4) the presence of signals of directional selection to cold climate for polymorphic variants of UCP genes. As a result of the evaluation, the highest scores for cold adaptation traits were recorded for polymorphic variants rs3811787 of the UCP1 gene and rs1800849 of the UCP3 gene. We suggest that the results obtained indicate the importance of uncoupling proteins UCP1 and UCP3 in human adaptation to cold through processes of non-shivering and shivering thermogenesis.