title: Lineage specific evolution of the VNTR composite retrotransposon central domain and its role in retrotransposition of gibbon LAVA elements.
abstract: BACKGROUND
  VNTR (Variable Number of Tandem Repeats) composite retrotransposons - SVA (SINE-R-VNTR-Alu), LAVA (LINE-1-Alu-VNTR-Alu), PVA (PTGR2-VNTR-Alu) and FVA (FRAM-VNTR-Alu) - are specific to hominoid primates. Their assembly, the evolution of their 5' and 3' domains, and the functional significance of the shared 5' Alu-like region are well understood. The central VNTR domain, by contrast, has long been assumed to represent a more or less random collection of 30-50 bp GC-rich repeats. It is only recently that it attracted attention in the context of regulation of SVA expression.
  
  
  RESULTS
  Here we provide evidence that the organization of the VNTR is non-random, with conserved repeat unit (RU) arrays at both the 5' and 3' ends of the VNTRs of human, chimpanzee and orangutan SVA and gibbon LAVA. The younger SVA subfamilies harbour highly organized internal RU arrays. The composition of these arrays is specific to the human/chimpanzee and orangutan lineages, respectively. Tracing the development of the VNTR through evolution we show for the first time how tandem repeats evolve within the constraints set by a functional, non-autonomous non-LTR retrotransposon in two different families - LAVA and SVA - in different hominoid lineages. Our analysis revealed that a microhomology-driven mechanism mediates expansion/contraction of the VNTR domain at the DNA level. Elements of all four VNTR composite families have been shown to be mobilized by the autonomous LINE1 retrotransposon in trans. In case of SVA, key determinants of mobilization are found in the 5' hexameric repeat/Alu-like region. We now demonstrate that in LAVA, by contrast, the VNTR domain determines mobilization efficiency in the context of domain swaps between active and inactive elements.
  
  
  CONCLUSIONS
  The central domain of VNTR composites evolves in a lineage-specific manner which gives rise to distinct structures in gibbon LAVA, orangutan SVA, and human/chimpanzee SVA. The differences observed between the families and lineages are likely to have an influence on the expression and mobilization of the elements.
authors.affiliation: Institute for Interdisciplinary Research in Bio-Nano-Sciences, Molecular Biology Center, Babes-Bolyai-University, Treboniu Laurian Street 42, Cluj-Napoca, RO-400271, Romania. iulia.lupan@gmail.com.
authors.forename: Iulia
authors.initials: I
authors.lastname: Lupan
authors.affiliation: Institute for Interdisciplinary Research in Bio-Nano-Sciences, Molecular Biology Center, Babes-Bolyai-University, Treboniu Laurian Street 42, Cluj-Napoca, RO-400271, Romania. bulzu_paul@yahoo.co.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Bulzu
authors.affiliation: Institute for Interdisciplinary Research in Bio-Nano-Sciences, Molecular Biology Center, Babes-Bolyai-University, Treboniu Laurian Street 42, Cluj-Napoca, RO-400271, Romania. opopescu.ubbcluj@gmail.com.|Institute of Biology, Romanian Academy, Bucharest, Romania. opopescu.ubbcluj@gmail.com.
authors.forename: Octavian
authors.initials: O
authors.lastname: Popescu
authors.affiliation: Institute for Interdisciplinary Research in Bio-Nano-Sciences, Molecular Biology Center, Babes-Bolyai-University, Treboniu Laurian Street 42, Cluj-Napoca, RO-400271, Romania. annette.damert@gmx.de.
authors.forename: Annette
authors.initials: A
authors.lastname: Damert
mesh_terms: D020087:Alu Elements / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D008040:Genetic Linkage; D006801:Humans; D002679:Pan troglodytes / Q000235:genetics; D011323:Primates / Q000235:genetics*; D018626:Retroelements / Q000235:genetics*; D016415:Sequence Alignment; D020080:Tandem Repeat Sequences / Q000235:genetics*
chemical_list: D018626:Retroelements