Global assessment of organ specific basal gene expression over a diurnal cycle with analyses of gene copies exhibiting cyclic expression patterns

Background Studying functional divergences between paralogs that originated from genome duplication is a significant topic in investigating molecular evolution. Genes that exhibit basal level cyclic expression patterns including circadian and light responsive genes are important physiological regulators. Temporal shifts in basal gene expression patterns are important factors to be considered when studying genetic functions. However, adequate efforts have not been applied to studying basal gene expression variation on a global scale to establish transcriptional activity baselines for each organ. Furthermore, the investigation of cyclic expression pattern comparisons between genome duplication created paralogs, and potential functional divergence between them has been neglected. To address these questions, we utilized a teleost fish species, Xiphophorus maculatus, and profiled gene expression within 9 organs at 3-h intervals throughout a 24-h diurnal period. Results Our results showed 1.3–21.9% of genes in different organs exhibited cyclic expression patterns, with eye showing the highest fraction of cycling genes while gonads yielded the lowest. A majority of the duplicated gene pairs exhibited divergences in their basal level expression patterns wherein only one paralog exhibited an oscillating expression pattern, or both paralogs exhibit oscillating expression patterns, but each gene duplicate showed a different peak expression time, and/or in different organs. Conclusions These observations suggest cyclic genes experienced significant sub-, neo-, or non-functionalization following the teleost genome duplication event. In addition, we developed a customized, web-accessible, gene expression browser to facilitate data mining and data visualization for the scientific community.

No Predictable Relationship Between Presacral Vertebral Number and Hes7 Intron Number Across Mammals

In mammals, the number of vertebrae and the somites they derive from is highly limited. Nevertheless, there are some lineages that have an increased number of presacral vertebrae and thus an elongated trunk. This suggests that somitogenesis, the process of somite formation in early development, is altered in these lineages. According the ‘clock and wavefront’ model of somitogenesis, temporal information of somite boundary formation is generated by a traveling wave of cyclic expression of oscillator genes. Hes7 has been suggested to be a key oscillator gene of this molecular segmentation clock. A previous study showed that reducing the number of introns within the Hes7 gene results in a more rapid tempo of Hes7 oscillation and an increased number of presacral vertebrae. Variation in Hes7 intron number could therefore be a potential evolutionary mechanism for varying vertebral number across mammals. In order to test this hypothesis, Hes7 intron number is here compared to presacral vertebral number across a variety of mammals.No significant relationship between both metrics could be detected as their variation across the mammalian phylogeny is fundamentally different. Integrating our data in the previously published mathematical model of Hes7 oscillation confirms the finding that variation in intron number does not predict variation in presacral vertebrae, rendering a direct causal relationship unlikely. However, our data support the previous suggestion that at least two introns are required for Hes7 pace making function of the segmentation clock.

Circadian production of melatonin in cartilage modifies rhythmic gene expression

Endochondral ossification, including bone growth and other metabolic events, is regulated by circadian rhythms. Herein, we provide evidence that melatonin has a direct effect on the circadian rhythm of chondrocytes. We detected mRNA expression of the genes which encode the melatonin-synthesizing enzymes AANAT (arylalkylamine N-acetyltransferase) and HIOMT (hydroxyindole O-methyltransferase), as well as the melatonin receptors MT1 and MT2 in mouse primary chondrocytes and cartilage. Production of melatonin was confirmed by mass spectrometric analysis of primary rat and chick chondrocytes. Addition of melatonin to primary BALB/c mouse chondrocytes caused enhanced cell growth and increased expression of Col2a1, Aggrecan and Sox9, but inhibited Col10a1 expression. Addition of luzindole, an MT1 and MT2 antagonist, abolished these effects. These data indicate that chondrocytes produce melatonin, which regulates cartilage growth and maturation via the MT1 and MT2 receptors. Kinetic analysis showed that melatonin caused rapid upregulation of Aanat, Mt1, Mt2 and Pthrp expression, followed by Sox9 and Ihh. Furthermore, expression of the clock gene Bmal1 was induced, while that of Per1 was downregulated. Chronobiological analysis of synchronized C3H mouse chondrocytes revealed that melatonin induced the cyclic expression of Aanat and modified the cyclic rhythm of Bmal1, Mt1 and Mt2. In contrast, Mt1 and Mt2 showed different rhythms from Bmal1 and Aanat, indicating the existence of different regulatory genes. Our results indicate that exogenous and endogenous melatonin work in synergy in chondrocytes to adjust rhythmic expression to the central suprachiasmatic nucleus clock.

Expression of sugarcane genes associated with perception of photoperiod and floral induction reveals cycling over a 24-hour period

The genetic network resulting in the production of an inflorescence is complex, involving one or more pathways including the photoperiod, maturity, gibberellin and autonomous pathways, and induction and repression of genes along the pathways. Understanding the cyclic expression profile of genes involved with photoperiod perception and floral pathway induction in sugarcane, an intermediate–short day plant (ISD), is crucial for identifying key genes and understanding how the profile changes in response to floral induction signals under decreasing daylengths. Homologues of 21 genes, and some gene alleles, associated with photoperiod perception and the flower induction pathway were examined in sugarcane variety Q174 over a 24-h light-dark cycle. The strongest expression of these genes was seen in the immature spindle leaves and levels of expression generally decreased with increasing leaf age. Significant changes in gene expression levels during a 24-h cycle were observed for 16 of the 21 genes tested. We have now defined an important baseline for expression patterns over a 24-h cycle in non-inductive conditions in sugarcane. These results can be utilised to select the optimal time for detecting changes during floral induction, differences between varieties that are responsive/non-responsive to photoperiod induction, and to identify genes that may be manipulated to enhance or inhibit flowering.

Spatial stochastic modelling of the Hes1 gene regulatory network: intrinsic noise can explain heterogeneity in embryonic stem cell differentiation

Individual mouse embryonic stem cells have been found to exhibit highly variable differentiation responses under the same environmental conditions. The noisy cyclic expression of Hes1 and its downstream genes are known to be responsible for this, but the mechanism underlying this variability in expression is not well understood. In this paper, we show that the observed experimental data and diverse differentiation responses can be explained by a spatial stochastic model of the Hes1 gene regulatory network. We also propose experiments to control the precise differentiation response using drug treatment.

Hormonal Link to Autoimmune Allergies

IgE recognition of autoantigens might augment allergic inflammation in the absence of exogenous allergen exposure. Among allergy and autoimmunity, there is disproportionate representation of males before puberty and females after puberty, suggesting a role for sex hormones. Hormone allergy is an allergic reaction where the offending allergens are one's own hormones. It is an immune reaction to the hormones, which can interfere with the normal function of the hormones. It can occur perimenstrually in women along with the variation in menstrual cycle. The perimenstrual allergies are about the cyclic abundance of the hormone causing a cyclic expression of allergic symptoms. The inflammatory mechanisms of allergic reactions to hormone allergens, which are intrinsic to the body, are the same as the mechanisms of allergic reactions to external allergens.