Biology subjects

Hogenesch, J.

Publications and source records attributed to Hogenesch, J..

3 recordsLinked to original sources

bioRxiv2018

Population level rhythms in human skin: implications for circadian medicine

Skin is the largest organ in the body and serves important barrier, regulatory, and sensory functions. Like other tissues, skin is subject to temporal fluctuations in physiological responses under both homeostatic and stressed states. To gain insight into these fluctuations, we investigated the role of the circadian clock in the transcriptional regulation of epidermis using a hybrid experimental design, where a limited set of human subjects (n=20) were sampled throughout the 24 h cycle and a larger population (n=219) were sampled once. By looking at pairwise correlations of core clock genes in 298 skin samples, we found a robust circadian oscillator in skin at the population level. Encouraged by this, we used CYCLOPS to reconstruct the temporal order of all samples and identified hundreds of rhythmically-expressed genes at the population level in human skin. We compared these results with published time-series skin data from mouse and show strong concordance in circadian phase across species for both transcripts and pathways. Further, like blood, skin is readily accessible and a potential source of biomarkers. Using ZeitZeiger, we identified a biomarker set for human skin that is capable of reporting circadian phase to within 3 h from a single sample. In summary, we show rhythms in human skin that persist at the population scale and a path to develop robust single-sample circadian biomarkers.\n\nOne Sentence SummaryHuman epidermis shows strong circadian rhythms at the population scale and provides a better source for developing robust, single-sample circadian phase biomarkers than human blood.

systems biology↗

bioRxiv2018

Systematic analysis of mouse genome reveals distinct evolutionary and functional properties among circadian and ultradian genes

In living organisms, biological clocks regulate 24 h (circadian) molecular, physiological, and behavioral rhythms to maintain homeostasis and synchrony with predictable environmental changes. Harmonics of these circadian rhythms having periods of 8 hours and 12 hours (ultradian) have been documented in several species. In mouse liver, harmonics of the 24-hour period of gene transcription hallmarked genes oscillating with a frequency two or three times faster than the circadian circuitry. Many of these harmonic transcripts enriched pathways regulating responses to environmental stress and coinciding preferentially with subjective dawn and dusk. We hypothesized that these stress anticipatory genes would be more evolutionarily conserved than background circadian and non-circadian genes. To investigate this issue, we performed broad computational analyses of genes/proteins oscillating at different frequency ranges across several species and showed that ultradian genes/proteins, especially those oscillating with a 12-hour periodicity, are more likely to be of ancient origin and essential in mice. In summary, our results show that genes with ultradian transcriptional patterns are more likely to be phylogenetically conserved and associated with the primeval and inevitable dawn/dusk transitions.

bioinformatics↗

bioRxiv2017

Reported Drosophila Courtship Song Rhythms Remain Data Analysis Artifacts

From 1980 to 1992, a series of influential papers reported on the discovery, genetics, and evolution of a periodic cycling of the interval between Drosophila male courtship song pulses. The molecular mechanisms underlying this periodicity were never described. To reinitiate investigation of this phenomenon, we performed automated segmentation of songs, but failed to detect the proposed periodicity [Arthur BJ et al. (2013) BMC Biol 11:11; Stern DL (2014) BMC Biol 12:38]. Kyriacou CP et al. [(2017) PNAS 114:1970-1975] report that we failed to detect song rhythms because i) our flies did not sing enough and ii) our segmenter did not identify many of the song pulses. Kyriacou et al. manually annotated a subset of our recordings and reported that two strains displayed rhythms with genotype-specific periodicity, in agreement with their original reports. We cannot replicate this finding and show that the manually-annotated data, the original automatically segmented data, and a new data set provide no evidence for either the existence of song rhythms or song periodicity differences between genotypes. Furthermore, we have re-examined our methods and analysis and find that our automated segmentation method was not biased to prevent detection of putative song periodicity. We conclude that there is currently no evidence for the existence of Drosophila courtship song rhythms.\n\nSignificance statementPrevious studies have reported that male vinegar flies sing courtship songs with a periodic rhythm of approximately 55 seconds. Several years ago, we showed that we could not replicate this observation. Recently, the original authors have claimed that we failed to find rhythms because 1) our flies did not sing enough and 2) our software for detecting song did not detect all song events. They claimed that they could detect rhythms in song annotated by hand. We report here that we cannot replicate their observation of rhythms in the hand-annotated data or in any dataset and that our original methods were not biased against detecting rhythms. We conclude that song rhythms cannot be detected.

animal behavior and cognition↗