title: 5'-Transducing SVA retrotransposon groups spread efficiently throughout the human genome.
abstract: SVA elements represent the youngest family of hominid non-LTR retrotransposons, which alter the human genome continuously. They stand out due to their organization as composite repetitive elements. To draw conclusions on the assembly process that led to the current organization of SVA elements and on their transcriptional regulation, we initiated our study by assessing differences in structures of the 116 SVA elements located on human chromosome 19. We classified SVA elements into seven structural variants, including novel variants like 3'-truncated elements and elements with 5'-flanking sequence transductions. We established a genome-wide inventory of 5'-transduced SVA elements encompassing approximately 8% of all human SVA elements. The diversity of 5' transduction events found indicates transcriptional control of their SVA source elements by a multitude of external cellular promoters in germ cells in the course of their evolution and suggests that SVA elements might be capable of acquiring 5' promoter sequences. Our data indicate that SVA-mediated 5' transduction events involve alternative RNA splicing at cryptic splice sites. We analyzed one remarkably successful human-specific SVA 5' transduction group in detail because it includes at least 32% of all SVA subfamily F members. An ancient retrotransposition event brought an SVA insertion under transcriptional control of the MAST2 gene promoter, giving rise to the primal source element of this group. Members of this group are currently transcribed. Here we show that SVA-mediated 5' transduction events lead to structural diversity of SVA elements and represent a novel source of genomic rearrangements contributing to genomic diversity.
authors: Fachgebiet PR2/Retroelemente, Paul-Ehrlich-Institut, D-63225 Langen, Germany.
authors: Annette
authors: A
authors: Damert
authors: Julija
authors: J
authors: Raiz
authors: Axel V
authors: AV
authors: Horn
authors: Johannes
authors: J
authors: Löwer
authors: Hui
authors: H
authors: Wang
authors: Jinchuan
authors: J
authors: Xing
authors: Mark A
authors: MA
authors: Batzer
authors: Roswitha
authors: R
authors: Löwer
authors: Gerald G
authors: GG
authors: Schumann
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D019143:Evolution, Molecular; D020224:Expressed Sequence Tags; D014644:Genetic Variation; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008957:Models, Genetic; D016254:Mutagenesis, Insertional; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D018626:Retroelements / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D008869:Microtubule-Associated Proteins; D018626:Retroelements; C503880:MAST2 protein, human; D017346:Protein Serine-Threonine Kinases