The Evidence for Increased L1 Activity in the Site of Human Adult Brain Neurogenesis

Abstract

Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus—the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory.

Additional Information

© 2015 Kurnosov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: May 8, 2014. Accepted: January 4, 2015. Published: February 17, 2015. We thank Dr. Tim Holland-Letz (DKFZ, Heidelberg) for help with statistical analysis. We thank Dr David Akopian for the help in manuscript preparation. Funding provided by RFBR-12-04-33065 Russian Foundation for Basic Research http://www.rfbr.ru/rffi/eng to IZM, RFBR-11-04-01159 Russian Foundation for Basic Research http://www.rfbr.ru/rffi/eng to YBL and state contract 14.604.21.0118 https://sstp.ru to YBL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author Contributions: Conceived and designed the experiments: AAK SVU KVK IZM YBL. Performed the experiments: AAK SVU AAM AYK. Analyzed the data: AAK VIN MS MVP. Contributed reagents/ materials/analysis tools: KVK. Wrote the paper: AAK KVK IZM.

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