![]() TEs are repetitive DNA sequences, typically ranging in length from 100 to 10,000 bp, capable of colonizing new genomic locations with copies of themselves. The peculiar ability of retrotransposon systems to support conversion from RNA to DNA incessantly contributes new sequences, potentially encoding new protein/RNA molecules or providing new cis-regulatory functions that selection can act on to produce genomic and organismal innovations. ![]() While the so-called DNA transposons employ a mechanism directly moving DNA segments from one genomic location to another, the heterogeneous class of TEs referred to as retrotransposons (or retroelements) do so through reverse transcription of an RNA copy of the original element, thereby affecting genome composition through the constant introduction of new DNA material. By allowing TE retention, TE silencing mechanisms have provided genomes with large pools of latent functional elements poised for exaptation. Since TEs replicate as genomic parasites, eukaryotic host organisms have co-evolved TE silencing systems largely based on the deposition of repressive epigenetic marks, of which the effect on the epigenome accompanied the effect of TE on the genome over the course of evolution. Although they represent a constant challenge for genome stability, TEs have at the same time introduced potentially fruitful changes into genomes both by driving genomic rearrangements (resulting, for example, in gene duplication) and by exaptation of TE-derived sequences. We review here a large body of recent studies lending support to the idea that retrotransposon-dependent evolutionary novelties were crucial for the emergence of mammalian, primate and human peculiarities of brain morphology and function.Ī large fraction of most eukaryotic genomes is constituted by transposable elements (TEs), interspersed repeats of which the high copy number reflects mobile DNA integration events that occurred countless times throughout evolutionary history. ![]() Accordingly, an increasing variety of neurodevelopmental and neurodegenerative conditions are being recognized to be associated with retrotransposon dysregulation. Retrotransposon-derived sequences have recently been implicated in multiple layers of gene regulation in the brain, from transcriptional and post-transcriptional control to both local and large-scale three-dimensional chromatin organization. Among mammals, hominids and especially humans display an extraordinarily expanded cortical volume, an enrichment of the repertoire of neural cell types and more elaborate patterns of neuronal connectivity. Among the features distinguishing mammals from all other vertebrates, the presence of a neocortex with a peculiar neuronal organization, composition and connectivity is perhaps the one that, by affecting the cognitive abilities of mammals, contributed mostly to their evolutionary success. Retrotransposons, a large and diverse class of transposable elements that are still active in humans, represent a remarkable force of genomic innovation underlying mammalian evolution. ![]()
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