Diurnal transcriptome atlas of a primate across major neural and peripheral tissues

Ludovic S Mure, Hiep D Le, Giorgia Benegiamo, Max W Chang, Luis Rios, Ngalla Jillani, Maina Ngotho, Thomas Kariuki, Ouria Dkhissi-Benyahya, Howard M Cooper, Satchidananda Panda, Science 359:eaao0318 (2018)

So many of us wake up and want—no need—our caffeine fix in the morning before we start our day.  This conditioning may reflect underlying processes in the body relating to our circadian rhythm.  The circadian rhythm is the cycling that happens based on a 24-hr clock, relating, in part, to the sun’s daily cycle.  Research recently published by Salk Institute scientists and colleagues (Mure et al. 2018) Science explores how a wide range of tissues individually respond to a circadian rhythm pattern.

Researchers conducted a comprehensive analysis of 64 tissue types of baboons identifying that each tissue type show rhythmic gene expression.  Analyzing >25,000 gene transcripts, ~11,000 were common in all 64 tissue types, inclusive of the 22 brain regions; yet, similar tissues clustered together in a principal component analysis of the transcriptomes.  Surprisingly, while the majority (76.7%) of the genes that were found to cycle as rhythmic genes are ubiquitously expressed genes (UEGs) that are for necessary cellular functions, they did not cycle universally in all tissue types.  This finding implies that there is tissue-specific regulation and perhaps organ-specific modulation of cellular functions.

The most genes (~3,000) found to cycle in some tissues (e.g., thyroid, stomach fundus, gastrocnemian muscle, paraventricular nucleus, and prefrontal cortex) was 15x greater than the mere 200 genes found cycling other tissues (e.g., pineal, mesenteric lymphonodes, supraoptic nucleus, lateral hypothalamus, and bone marrow).  Using a method called MetaCycle, which includes multiple algorithms to calculate periodicity and rhythmicity, the scientists suggest the data support the hypothesis that the rhythmic transcription reduces or optimizes energy expenditure in gene expression.

A unique component of this study was that it studied baboons, which are diurnal, as opposed to previous vertebrate work with the nocturnal mouse.  Consequently, results identify the expression of the rhythmic genes had two major peaks:  early afternoon and late night/dawn.  The baboon peak phase of expression were shifted by approximately 12 hours when compared to the mouse.

The implications of these findings relate directly to human health.  The rhythmic nature of 82.2% of genes that code for proteins are potentially druggable targets—as identified by the U.S. Food and Drug Administration.  Furthermore, disruptions in circadian rhythms are linked to numerous diseases and disorders.  Understanding the circadian rhythms of tissues as a baseline created by this study set the ground work for differing genetic and environmental factors that could relate to human pathologies.