A circadian gene expression atlas in mammals: implications for biology and medicine.
Level 5 - mechanism / opinion, no new human data
Preclinical animal model study (mouse transcriptomic profiling) without human clinical data.
PubMed 25349387 · doi:10.1073/pnas.1408886111
What was done
Researchers profiled circadian gene expression across 12 mouse organs over time using RNA sequencing (RNA-seq) and DNA microarrays. They analyzed genomic characteristics, spliceforms, pathway coordination, and oscillation patterns of protein-coding genes and noncoding RNAs (ncRNAs), and mapped rhythmic gene products against target databases for best-selling and World Health Organization essential medicines.
What was found
Circadian transcriptional rhythmicity was observed in 43% of all protein-coding genes across the body, occurring predominantly in an organ-specific pattern. Rhythmic expression peaked before dawn and dusk. Oscillating genes were systematically longer, had more splice variants, and clustered together genomically compared to non-oscillating genes. Over 1,000 known and novel ncRNAs demonstrated circadian oscillations. The majority of top-selling pharmaceuticals and WHO essential medicines directly target products of rhythmic genes.
Why it matters
This study provides a comprehensive map of systemic circadian gene regulation in mammals, establishing a biological rationale for timed drug administration (chronotherapy) across diverse therapeutic areas.
Limits
The findings derive entirely from mice; human tissue rhythmicity is inferred by homology rather than directly measured. Sample size (number of animals and sampled timepoints) is not stated in the abstract. Clinical chronotherapeutic efficacy cannot be determined from gene expression data alone.
Cited by
- supports Between 3,000 and 5,000 genes in the liver (representing nearly 30% of the expressed genome) are cyclically turned on and off depending on time of day.