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The human genome as an RNA machine

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In association with Trinity College Science Society

It is now evident that the majority of the genomes of all animals, from nematodes to mammals, is transcribed, apparently in a developmentally regulated manner. I will present evidence from analysis of over 500 sequenced genomes that the number of regulatory genes in prokaryotes scales quadratically with genome size, and that prokaryotes have reached the limit of the capacity of a solely protein-based regulatory architecture probably early in evolution. This also implies that the complex eukaryotes have breached this limit, most likely by the cooption of RNA as a quasi-digital regulatory system that directs the trajectories of differentiation and development, and that the emergence of this system was the critical precondition for the emergence of complex organisms. I will also discuss the questionable assumptions that underlie the current view that only ~5% of the human genome is under selection, and present an alternative view that the much if not most of the genome is functional and comprised of different types of sequences, mainly regulatory sequences, that are evolving at different rates under different structure-function constraints and different selection pressures. I will show that there is dynamic expression of thousands of ncRNAs during the differentiation of embryonic stem cells, neuronal cells, muscle, gonadal ridge and immune cells, and that a large number of ncRNAs are expressed in the brain, many in precise locations in the cortex, hippocampus, olfactory bulb, cerebellum and other places, the majority of which (where there is sufficient resolution to judge) are trafficked to specific subcellular compartments. Finally I will discuss the role of RNA signaling in the formation of epigenetic memory, and the role of RNA editing in the evolution of higher order cognition.

This talk is part of the Cambridge University Biological Society series.

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