Leafing through the Literature

Thalyana Smith-Vikos

Highlighting recently published articles in molecular biology, genetics, and other hot topics

Trusting Your Gut Microbiota

Changes in human gut microbiota have been linked to an increasing likelihood of developing metabolic diseases. Karlsson et al. sequenced the fecal metagenome of 145 European women with normal, impaired or diabetic glucose control. From these profiles, the researchers developed a mathematical model to identify cases of type 2 diabetes, and predicted an individual’s diabetes-like metabolism by applying the model to women with impaired glucose control. They also discriminated between metagenomic markers for type 2 diabetes in their European cohort compared to a recently published Chinese cohort.

Modi et al. were interested in studying changes in murine gut microbiota due to antibiotic treatment. Specifically, they sequenced the bacterial phageome as a mechanism of identifying bacterial adaptation in the presence of antibiotic stress. They found that antibiotic treatment leads to an up-regulation of phage genes that confer specific or broad drug resistance, and phages specifically improve the resistance of gut microflora. Antibiotic treatment also leads to increased gene exchange between phages and bacteria, and the authors hypothesized that the phageome may maintain gut microflora robustness under antibiotic treatment.

Selecting Transcription Factor Binding Sites, Naturally

Arbiza et al. elegantly explored how gene regulation has affected human evolution. They used whole-genome sequencing and ChIP-Seq to identify mutations which demonstrate that natural selection has impacted human transcription factor binding sites since our divergence from chimpanzees. The researchers discovered that, while protein-coding genes have experienced more selection pressure, certain transcription factor binding sites also show signs of evolutionary adaptation, in cases of both substitutions and polymorphisms. These findings may substantially alter how we view the development of human diseases.

Carbon Dating Adult Hippocampal Neurons

While adult-born hippocampal neurons have been well-studied in rodents by contributing to cognitive plasticity, the effects of hippocampal neurogenesis in human adults remained elusive. By measuring concentration of 14C in new born neurons, Spalding et al. were able to observe the growth of human hippocampal neurons. 700 neurons are born every day in the hippocampus, and 1.75% of the neurons are replenished annually, but this number declines slightly in older adults. The authors concluded that hippocampal neurogenesis is in fact present throughout human adulthood and may contribute to brain function.

Long-Distance Chaperoning of Tissue Proteostasis

van Oosten-Hawle et al. used the nematode C. elegans as a model for studying how different tissues in an organism are each protected from proteotoxic stress. The authors saw that disruption of proteostasis in muscle cells consequently induces a systemic stress response across various tissues. Additionally, suppression of this protein misfolding in muscle cells is possible by elevating levels of the chaperone HSP90 in intestinal or neuronal cells just as effectively as inducing HSP90 expression in muscle cells themselves. Transcriptional regulation of HSP90 in these various tissues is mediated by PHA-4/FoxA and HSF-1. Thus, a localized area of protein misfolding is regulated by transcellular chaperone signaling to promote increased survival of the organism.

The Circle of Life (of an mRNA, that is)

When investigating how yeast mRNAs are degraded by the decaysome, Haimovich et al. observed that defects in multiple decaysome factors also led to down-regulation of mRNA transcription. The researchers further discovered that these decaysome factors are found in both the nucleus and cytoplasm and frequently shuttle between the two. These mRNA degradation factors are also thought to bind ~30bp upstream of transcription start sites and directly activate mRNA synthesis. Thus, maintaining mRNA levels follows a circular mechanism: transcription and mRNA decay are highly linked processes and are concurrently involved in regulating gene expression.