The evidence for increased L1 activity in the site of human adult brain neurogenesis.

Alexey A Kurnosov,Ilgar Z Mamedov,Yuri B Lebedev,Alexander Yu Komkov,Konstantin V Khodosevich,Mikhail Shugay,Svetlana V Ustyugova,Vadim I Nazarov,Anastasia A Minervina,Mikhail V Pogorelyy,Jialin Charles Zheng

doi:10.1371/journal.pone.0117854

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.

Highlights

40% of the human genome is comprised of multiple copies of retroelements (REs) due to their winning streak in the course of mammalian evolution [1]
The major groups of retroelements present in the human genome are the Long Terminal Repeats (LTR) retrotransposons, the Long Interspersed Nuclear Elements (LINEs), the Short Interspersed Nuclear Elements (SINEs), and the SINE-R/VNTR/Alu (SVA) elements
The subgranular zone (SGZ) of the dentate gyrus (DG) together with the subventricular zone (SVZ) of the lateral ventricles are the only regions in the mammalian brain that persist in generating new neurons throughout the animal life [29]

Summary

Introduction

40% of the human genome is comprised of multiple copies of retroelements (REs) due to their winning streak in the course of mammalian evolution [1]. The major groups of retroelements present in the human genome are the Long Terminal Repeats (LTR) retrotransposons, the Long Interspersed Nuclear Elements (LINEs), the Short Interspersed Nuclear Elements (SINEs) (most of which belong to the Alu family), and the SINE-R/VNTR/Alu (SVA) elements. Polymorphic insertions found in the genome of a part of human population usually result from the recent retrotranspositional activity of REs which have retained the capacity to amplify themselves. These insertions belong to the evolutionary young

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