Upregulation of cathepsin L gene under mild cold conditions in young Japanese male adults

Yoshiki Yasukochi,Takafumi Maeda,Sora Shin,Hitoshi Wakabayashi

doi:10.1186/s40101-021-00267-9

Abstract

BackgroundPhysiological thermoregulatory systems in humans have been a key factor for adaptation to local environments after their exodus from Africa, particularly, to cold environments outside Africa. Recent studies using high-throughput sequencing have identified various genes responsible for cold adaptation. However, the molecular mechanisms underlying initial thermoregulation in response to acute cold exposure remain unclear. Therefore, we investigated transcriptional profiles of six young Japanese male adults exposed to acute cold stress.MethodsIn a climatic chamber, the air temperature was maintained at 28°C for 65 min and was then gradually decreased to 19°C for 70 min. Saliva samples were obtained from the subjects at 28°C before and after 19°C cold exposure and were used for RNA sequencing.ResultsIn the cold exposure experiment, expression levels of 14 genes were significantly changed [false discovery rate (FDR) < 0.05] although the degree of transcriptional changes was not high due to experimental conditions or blunted transcriptional reaction in saliva to cold stress. As a result, differential gene expression analyses detected the cathepsin L (CTSL) gene to be significantly upregulated, with FDR < 0.05 and log2 fold change value > 1; thus, this gene was identified as a differentially expressed gene. Given that the cathepsin L protein is related to invasion of the novel coronavirus (SARS-CoV-2), mild cold stress might alter the susceptibility to coronavirus disease-19 in humans. The gene ontology enrichment analysis for 14 genes with FDR < 0.05 suggested that immune-related molecules could be activated by mild cold stress.ConclusionsThe results obtained from this study indicate that CTSL expression levels can be altered by acute mild cold stress.

Highlights

Physiological thermoregulatory systems in humans have been a key factor for adaptation to local environments after their exodus from Africa, to cold environments outside Africa
A previous study has reported that positive natural selection may have operated on a regulatory genetic variant near the transient receptor potential cation channel subfamily M member 8 (TRPM8) gene in Eurasian populations for cold adaptation [25], whereas strong signals of positive selection were detected in genomic regions containing carnitine palmitoyltransferase 1A (CPT1A) and LDL receptor-related protein 5 (LRP5) genes on chromosome 11 in Northeastern Siberian populations [26]
The limited expression levels may be attributed to the following: (1) the intensity or duration of cold stress may have been insufficient to induce drastic transcriptional changes, (2) saliva samples containing buccal cells and leukocytes were less sensitive to cold exposure, (3) the timing of sample collection possibly decreases the statistical power to detect differentially expressed gene (DEG) because we investigated transcriptional profiles after cold exposure but not during the exposure, and (4) seasonal acclimatization related to the low outside temperature in winter (October to December) may have affected the sensitivity of transcriptional responses to cold exposure in this experiment

Summary

Introduction

Physiological thermoregulatory systems in humans have been a key factor for adaptation to local environments after their exodus from Africa, to cold environments outside Africa. Modern humans emerged in Africa ~300,000 to 200,000 years ago [1]; they dispersed worldwide from Africa many tens of thousands of years ago, but the timing remains controversial [2,3,4,5,6] This migration event is called “Out-of-Africa” and these migrating human populations have genetically adapted to various local environments [7, 8]. Single-nucleotide polymorphisms (SNPs) or haplotypes of UCP1 can affect adaptive responses to cold environments as well as the development of obesity through energy expenditure in human populations [19, 20] and even in Japanese individuals [21,22,23]. A previous study has reported that positive natural selection may have operated on a regulatory genetic variant near the transient receptor potential cation channel subfamily M member 8 (TRPM8) gene in Eurasian populations for cold adaptation [25], whereas strong signals of positive selection were detected in genomic regions containing carnitine palmitoyltransferase 1A (CPT1A) and LDL receptor-related protein 5 (LRP5) genes on chromosome 11 in Northeastern Siberian populations [26]

Methods

Results

Conclusion