Conservation of primordial ~12-hour ultradian gene programs in humans

Biological rhythms have important implications for human disease, as evidenced by the effects of disrupting the 24h circadian clock. While circadian rhythms are entrained to the once daily light-dark cycle of the sun, coastal marine organisms are known to exhibit 12h ultradian rhythms, corresponding to the twice daily movement of the tides. Human ancestors emerged from a circa-tidal environment millions of years ago. However, whether 12h ultradian rhythms are conserved in humans remains unknown. Here, we performed prospective, high temporal resolution transcriptome profiling in the peripheral white blood cells of three healthy subjects. Remarkably, all three subjects exhibited a shared transcriptional program demonstrating robust ~12h rhythms. Pathway analysis implicated 12h transcriptional oscillations primarily affected core cellular processes, including RNA and protein metabolism, with strong homology to the 12h gene programs previously identified in cnidarian marine species. These results establish the existence of 12h biological rhythms in humans. Such rhythms appear to have a primordial evolutionary origin dating back at least 700 million years and are likely to have far-reaching implications in human health and disease. Overall design: Blood samples were collected every two hours for a total of 48-hour period (D1 and D2) from three healthy individuals (S1, S2 and S3).