The Flow of the Gibbon LAVA Element Is Facilitated by the LINE-1 Retrotransposition Machinery

Abstract

LINE-Alu-VNTR-Alu-like (LAVA) elements comprise a family of non-autonomous, composite, non-LTR retrotransposons specific to gibbons and may have played a role in the evolution of this lineage. A full-length LAVA element consists of portions of repeats found in most primate genomes: CT-rich, Alu-like, and VNTR regions from the SVA retrotransposon, and portions of the AluSz and L1ME5 elements. To evaluate whether the gibbon genome currently harbors functional LAVA elements capable of mobilization by the endogenous LINE-1 (L1) protein machinery and which LAVA components are important for retrotransposition, we established a trans-mobilization assay in HeLa cells. Specifically, we tested if a full-length member of the older LAVA subfamily C that was isolated from the gibbon genome and named LAVAC, or its components, can be mobilized in the presence of the human L1 protein machinery. We show that L1 proteins mobilize the LAVAC element at frequencies exceeding processed pseudogene formation and human SVAE retrotransposition by > 100-fold and ≥3-fold, respectively. We find that only the SVA-derived portions confer activity, and truncation of the 3′ L1ME5 portion increases retrotransposition rates by at least 100%. Tagged de novo insertions integrated into intronic regions in cell culture, recapitulating findings in the gibbon genome. Finally, we present alternative models for the rise of the LAVA retrotransposon in the gibbon lineage.

Transposable elements: genome innovation, chromosome diversity, and centromere conflict

“…Although gibbons diverged from other hominids only 15–18 million years ago, the species complex is characterized by highly rearranged chromosomes (Carbone et al 2014 ); among the four genera of gibbons, the number of chromosomes varies from 38 to 52. The centromeres of the Eastern hoolock gibbon were found to contain a novel TE named LAVA, L INE- A lu- V NTR- A lu-like, consisting of pieces of these repetitive elements and classified as a non-autonomous composite element that can be mobilized by LINE1 (Carbone et al 2014 ; Carbone et al 2012 ; Meyer et al 2016 ). LAVA was subsequently found within centromeres of other gibbon species, yet shows a species-specific pattern of chromosome-delimited accumulation.…”

“…The observation that entire centromere regions carried a dense accumulation of a specific TE is not unique to gibbons as a similar phenomenon had been described in the wallaby species complex with a different TE, KERV (kangaroo endogenous retrovirus) (Bulazel et al 2007 ; Bulazel et al 2006 ; Metcalfe et al 2007 ; O'Neill et al, 1998 ). In both cases, epigenetic dysregulation of the TE through hypomethylation led to subsequent centromere restructuring and chromosome shuffling, likely caused by initial interspecific hybridization events (Fontdevila 2005 ; Metcalfe et al 2007 ; Meyer et al 2016 ; O'Neill and Carone, 2009 ; O'Neill et al, 2004 ; 1998 ).…”

Chromoanagenesis: a piece of the macroevolution scenario

“…They may promote adaptability of a population by generating changes in gene expression or promoting rapid chromosome restructuring [98,99]. For instance, in the gibbon genome, the insertion of the retro-transposon LAVA in genes implicated in cell cycle progression and chromosome segregation appears to be at the origin of a high rate of chromothripsis-related rearrangements leading to the accelerated evolution of the gibbon karyotype and the emergence of different gibbon lineages, with highly rearranged chromosomes [70,100]. Another example of speciation driven by massive chromosome rearrangements is the extensive chromosome reshuffling experienced by the marsupial family Macropodidae, with numerous interchromosomal rearrangements and diploid karyotype number ranging from 2n = 10 to 2n = 24 [101].…”

LINE-1 ORF1p does not determine substrate preference for human/orangutan SVA and gibbon LAVA

“…280 per myrs (split-time from chimpanzee 4-6 myrs ago). However, a direct comparison of these numbers might be misleading: to date there is no information available about the SVA expansion dynamics in orangutan over the last [14][15][16] myrs. An approximately constant rate over the entire period of time and bursts of amplification are equally possible.…”

“…As non-autonomous elements VNTR-composite retrotransposons are dependent on the proteins encoded by the autonomous LINE-1 (L1) element for their mobilization [ 11 – 14 ]. Across hominoids SVA/LAVA “pair” with L1 partners belonging to different subfamilies: LAVA with L1PA4 in gibbons, SVA pa with L1PA3 in orangutan and SVA hs with L1PA1 in human.…”