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Transposable elements and the evolution of the human brain

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If you have a question about this talk, please contact Caroline Newnham.

Host: Michael Imbeault

The complexity of human brain development differs markedly from other mammals and is thought be important for the emergence of higher cognitive functions. However, the precise genetic changes, as well as the existence of human-specific gene regulatory networks underlying the evolution of the human brain remains poorly explored. Most of our knowledge about human brain development is restricted to evolutionary conserved developmental pathways, while much less is known about primate- and human-specific developmental mechanisms. Identification of novel mechanisms that regulate human brain development is important for our understanding of the human brain and may also provide new links to the biology of human brain disorders.

About 50% of the human genome is composed of transposable elements (TEs). Since TEs have entered the genome as mobile elements there are major differences in the genomic composition of TEs between species. For example, hundreds of thousands of TEs, including e.g. LINE , SINE and LTR -type elements, are primate-specific and several thousands are human-specific. While a small number of these elements remain capable of transposing, i.e. move and amplify through a copy-and-paste mechanism, most are fixed in the genome as remnants of ancient transposition events.

My lab is currently investigating if TEs contribute to the evolution of the human brain. We have found a region- and developmental stage-specific expression pattern of TEs in the developing human brain, which is linked to a transcriptional network based on TEs. Several thousand TEs, many that are primate-specific, act as docking platforms for the epigenetic co-repressor protein TRIM28 , which results in the establishment of local heterochromatin around these TEs. This repressive transcriptional network modulates expression of protein-coding transcripts important for brain development, thereby providing an additional layer of transcriptional regulation. Our findings open up for several exciting future studies on the role of TEs as potential drivers of human brain evolution, their contribution to individual variation and the implication in human brain disorders.

This talk is part of the Genetics Seminar series.

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