The whale shark genome reveals how genomic and physiological properties scale with body size, bioRxiv, 2018-10-14

AbstractThe endangered whale shark (Rhincodon typus) is the largest fish on Earth and is a long-lived member of the ancient Elasmobranchii clade. To characterize the relationship between genome features and biological traits, we sequenced and assembled the genome of the whale shark and compared its genomic and physiological features to those of 81 animals and yeast. We examined scaling relationships between body size, temperature, metabolic rates, and genomic features and found both general correlations across the animal kingdom and features specific to the whale shark genome. Among animals, increased lifespan is positively correlated to body size and metabolic rate. Several genomic features also significantly correlated with body size, including intron and gene length. Our large-scale comparative genomic analysis uncovered general features of metazoan genome architecture GC content and codon adaptation index are negatively correlated, and neural connectivity genes are longer than average genes in most genomes. Focusing on the whale shark genome, we identified multiple features that significantly correlate with lifespan. Among these were very long gene length, due to large introns highly enriched in repetitive elements such as CR1-like LINEs, and considerably longer neural genes of several types, including connectivity, activity, and neurodegeneration genes. The whale shark’s genome had an expansion of gene families related to fatty acid metabolism and neurogenesis, with the slowest evolutionary rate observed in vertebrates to date. Our comparative genomics approach uncovered multiple genetic features associated with body size, metabolic rate, and lifespan, and showed that the whale shark is a promising model for studies of neural architecture and lifespan.

biorxiv genomics 0-100-users 2018

A Framework for Intelligence and Cortical Function Based on Grid Cells in the Neocortex, bioRxiv, 2018-10-13

AbstractHow the neocortex works is a mystery. In this paper we propose a novel framework for understanding its function. Grid cells are neurons in the entorhinal cortex that represent the location of an animal in its environment. Recent evidence suggests that grid cell-like neurons may also be present in the neocortex. We propose that grid cells exist throughout the neocortex, in every region and in every cortical column. They define a location-based framework for how the neocortex functions. Whereas grid cells in the entorhinal cortex represent the location of one thing, the body relative to its environment, we propose that cortical grid cells simultaneously represent the location of many things. Cortical columns in somatosensory cortex track the location of tactile features relative to the object being touched and cortical columns in visual cortex track the location of visual features relative to the object being viewed. We propose that mechanisms in the entorhinal cortex and hippocampus that evolved for learning the structure of environments are now used by the neocortex to learn the structure of objects. Having a representation of location in each cortical column suggests mechanisms for how the neocortex represents object compositionality and object behaviors. It leads to the hypothesis that every part of the neocortex learns complete models of objects and that there are many models of each object distributed throughout the neocortex. The similarity of circuitry observed in all cortical regions is strong evidence that even high-level cognitive tasks are learned and represented in a location-based framework.

biorxiv neuroscience 100-200-users 2018

Centrosome-nuclear envelope tethering and microtubule motor-based pulling forces collaborate in centrosome positioning during mitotic entry, bioRxiv, 2018-10-13

Centrosome positioning relative to the nucleus and cell shape is highly regulated across cell types, during cell migration and during spindle formation in cell division. Across most sexually reproducing animals, centrosomes are provided to the oocyte through fertilization and must be positioned properly to establish the zygotic mitotic spindle. How centrosomes are positioned in space and time through the concerted action of key mitotic entry biochemical regulators including Protein Phosphatase 2A (PP2A-B55SUR-6), biophysical regulators including Dynein and the nuclear lamina is unclear. Here, we uncover a role for PP2A-B55SUR-6 in regulating centrosome positioning. Mechanistically, PP2A-B55SUR-6 regulates nuclear size prior to mitotic entry, in turn affecting nuclear envelope-based Dynein density and motor capacity. Using computational simulations, PP2A-B55 SUR-6 regulation of nuclear size and nuclear envelope Dynein density were both predicted to be required for proper centrosome positioning. Conversely, compromising nuclear lamina integrity led to centrosome detachment from the nuclear envelope and migration defects. Removal of PP2A-B55SUR-6 and the nuclear lamina simultaneously further disrupted centrosome positioning, leading to unseparated centrosome pairs dissociated from the nuclear envelope. Taken together, we propose a model in which centrosomes migrate and are positioned through the concerted action of nuclear envelope-based Dynein pulling forces and cen-trosome-nuclear envelope tethering.

biorxiv cell-biology 0-100-users 2018

 

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