Mammalian non-LTR retrotransposons: For better or worse, in sickness and in health

Abstract

Transposable elements (TEs) have shared an exceptionally long coexistence with their host organisms and have come to occupy a significant fraction of eukaryotic genomes. The bulk of the expansion occurring within mammalian genomes has arisen from the activity of type I retrotransposons, which amplify in a “copy-and-paste” fashion through an RNA intermediate. For better or worse, the sequences of these retrotransposons are now wedded to the genomes of their mammalian hosts. Although there are several reported instances of the positive contribution of mobile elements to their host genomes, these discoveries have occurred alongside growing evidence of the role of TEs in human disease and genetic instability. Here we examine, with a particular emphasis on human retrotransposon activity, several newly discovered aspects of mammalian retrotransposon biology. We consider their potential impact on host biology as well as their ultimate implications for the nature of the TE–host relationship.

Extensive synteny conservation of holocentric chromosomes in Lepidoptera despite high rates of local genome rearrangements

“…The prevalence of non-LTR retrotransposons makes lepidopteran genomes different from that of Drosophila melanogaster, in which LTR retrotransposons are the most abundant (31). Both the rather high repeat coverage and the prevalence of non-LTR retrotransposons make lepidopteran genomes look like mammalian genomes (32,33).…”

Diverse cis factors controlling Alu retrotransposition: What causes Alu elements to die?

“…There are at least 15 examples of Ya5 elements that have recently inserted causing disease (Belancio et al 2008), despite there being only 3000 copies in the genome (Wang et al 2006). In contrast, the older subfamilies have a 300-fold greater copy number than Ya5 while having no detectable amplification rate, suggesting that there must be at least a 4500-fold enrichment in activity per Ya5 copy relative to the old Alu subfamily members.…”

“…To date, the exact reasons why these older Alu elements are ''dead'' or why only the younger Alu elements continue to amplify remain unclear. Surprisingly, Alu element insertions cause twice as much disease as L1 despite the fact that L1 is necessary for Alu activity (Belancio et al 2008).…”

“…Activity of the old AluJ/S subfamilies declined while being replaced by the younger Y subfamily (;100,000 copies) (Shen et al 1991). Subsets of the Y subfamilies are the only known Alu elements currently active in the human genome, with variants of the Y, Ya, and Yb lineages currently dominating activity (Deininger and Batzer 1999;Hedges et al 2004;Mills et al 2007;Belancio et al 2008). There are ;900,000 older subfamily elements in the genome, predominately variants of the Alu S and J (Wang et al 2006), and yet no de novo disease-associated insertions of these older elements have been found (Belancio et al 2008).…”

The human genome in the LINE of fire

“…Represented by the currently active LINE-1 or L1 elements, LINEs are autonomous TEs that propagate in the genome by making RNA copies of themselves that are subsequently reverse transcribed and integrated into the genome (2-4). As a result of their ongoing activity during the past 150 million years, L1 elements account for approximately one-third of the human genome, by way of selfmobilization (Ϸ500,000 copies) and transmobilization of nonautonomous Alu (Ϸ1,100,000 copies) and SVA (Ϸ3,000 copies) TEs and processed pseudogenes (Ϸ11,000 copies) (1)(2)(3)(4)(5). This high density of repetitive sequences poses a considerable threat to the stability of our genome, ranging from mutations and genomic alterations on TE insertion to large-scale genomic rearrangements triggered by recombination between nonallelic homologous TE sequences (2)(3)(4)6).…”