Consequences of ongoing retrotransposition in mammalian genomes

Abstract

Abstract:Retrotransposons can have significant influences on gene expression and genome stability through their ability to integrate reverse-transcript copies of their sequences at new genomic locations by retrotransposition. These elements have been long known to retrotranspose in mammalian germ cells to give rise to inherited insertion alleles, but more recent work has also shown that retrotransposition can occur in mammalian somatic cells, particularly in brain tissue and tumors. Retrotransposition makes appreciable contributions to spontaneous diseasecausing alleles in humans and a more significant contribution to spontaneous mutations in mice. Genome-wide studies have found high levels of polymorphic retrotransposon insertions in human populations that are consistent with ongoing retrotransposition. Many insertions do not disrupt exons, but insertions into introns or flanking genes can alter gene expression patterns, generate truncated or antisense gene transcripts, alter splicing patterns, or result in premature polyadenylation of gene transcripts. Furthermore, the very high genomic copy numbers of these elements can lead to nonallelic homologous recombination events that produce gene deletions/ duplications and genome rearrangements, and can also lead to evolution of particular insertions or types of elements to have cellular functions through exaptation. Mobility of these elements occurs despite multiple epigenetic mechanisms to restrict their expression. While the potential for retrotransposons to significantly influence mammalian health and cellular functions is clear, substantial research efforts will be needed to fully elucidate the actual contributions of natural levels of mobility of endogenous elements to the health and development of humans and other mammals.

L1 chimeric transcripts are expressed in healthy brain and their deregulation in glioma follows that of their host locus

“…Besides the consequences of retrotransposition (e.g . insertional mutagenesis, creation of new alternative splicing sites, promoting sequence transduction from the donor to new insertion sites) ( 3 ), L1 retrotransposons can also interfere with the transcriptional activity of the surrounding genomic sequences from their bidirectional promoter. Specifically, in addition to the sense promoter, the 5′ UTR of evolutionarily recent L1s also contain an anti-sense promoter (L1-ASP) that can produce transcripts from the 5′ UTR in antisense orientation to the adjacent genomic region.…”

Diversification and coevolution of the ghrelin/growth hormone secretagogue receptor system in vertebrates

“…) (Miki et al. ; Chan and Cheng ), retrotransposition (Maxwell ), or alternative splicing to eventually become a gene family. Whole‐genome duplication ( WGD ) has been considered as the most common mechanism resulting in the diversification of ligand and receptor gene families (Taylor et al.…”

“…The activation of heterotrimeric G protein mediates the actions of signaling proteins such as neuroendocrine peptides by allowing the translation of extracellular signals into the intracellular space (Kaiya et al 2008(Kaiya et al , 2014a. Receptors and their peptide ligands originated from common ancestral genes and may have diversified through gene duplication (Meyer and Schartl 1999;Meijer et al 2007) (Miki et al 1992;Chan and Cheng 2004), retrotransposition (Maxwell 2014), or alternative splicing to eventually become a gene family. Whole-genome duplication (WGD) has been considered as the most common mechanism resulting in the diversification of ligand and receptor gene families (Taylor et al 2003).…”

Μελέτη Του Ρόλου Των Ρετρομεταθετών Στοιχείων Στην Υπερδιέγερση Των Ωοθηκών Και Την Εμβρυογένεση

“…Στα ανθρώπινα έμβρυα παρατηρείται από το στάδιο των 8 του κάθε cDNA κλώνου, στη θέση στόχο. Η προσθήκη και η σύνδεση των νουκλεοτιδίων στα κενά που σχηματίζονται στα 5΄άκρα, πραγματοποιούνται από τη δράση των πρωτεϊνικών μηχανισμών του κυττάρου(49). Παρά το μικρό αριθμό αντιγράφων τους, η παρουσία τους φαίνεται να είναι απαραίτητη για το κύτταρο, καθώς για παράδειγμα τα LINEs-2 στοιχεία θεωρείται ότι αποσιωπούν ειδικά και ισχυρά τα Τκύτταρα(55).…”